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• New heteocyclic derivatives containing pyridine and pyrazole have been synthesized successfuly. • All newly produced compounds were characterized using mass, NMR, and IR spectra. • The new compounds were tested for anticancer effects on human cell lines (H460), (FaDu), and (Huh7). • Compounds 3, 8, 11 and 16 are secure and specific because their IC50 values on normal cell line are higher than their IC50 values on tested cancer cell lines. Cancer is a common public health disease causing mortality worldwide. Thus, providing novel chemotherapies that tackle breast cancer is of great interest. In this investigation, novel heterocyclic compounds with pyridine, pyrimidine, and pyrazole rings 2 – 16 were synthesized and characterized using a variety of spectrum analyses. All synthesized compounds were evaluated for their anticancer effects on human lung carcinoma cell line (H460), human pharynx squamous cell carcinoma cell line (FaDu), and common human hepatocellular carcinoma cell line (Huh7), compounds 3 (6-ethoxy-pyridine), 8 (pyridinyl-pyrazol) , 9 (pyridinyl- N, N -diacetylpyrazol), 11 (pyridinyl- N -(2,4-dinitrophenyl)pyrazole), 13 (pyridinyl-isoxazole) and 16 (pyridinyl-benzo[b][1,4]thiazepine) had the maximum anticancer activity against all examined cell lines. Based on these resultss, we are able to conclude that analoges 6-Ethoxy-pyridine 3 , Pyridinyl-pyrazol 8 , Pyridinyl-N-(2,4-dinitrophenyl)pyrazole 11 and Pyridinyl-benzo[b][1,4]thiazepine 16 are found to be secure and specific because their IC 50 values on normal cell line are higher than their IC 50 values on tested cancer cell lines. [Display omitted] [ABSTRACT FROM AUTHOR]

• A variety of pyrimidinyl oxa/thia/triazoles are prepared using trimethylsilyl isothiocyanate. • Docking results indicated that the compounds 3e, 5e, 7a have better docking scores than Chloramphenicol. • The compounds 3e, 5a, 5e have better docking scores than Fluconazole. • The unsubstituted, methyl and nitro substituted molecules showed greater antimicrobial activity. Organosilicon reagent-trimethylsilyl isothiocyanate, a common reagent for the development of 1,3,4-oxadiazoles, 1,3,4-thiadiazoles and 1,2,4-triazoles was reported by the reaction with heteroaromatic acid hydrazides under conventional and ultrasonication methodologies in a polar protic solvent, ethanol under appropriate conditions. Molecular docking studies were performed with the X-ray crystal structures of the target molecules (PDB ID: 2w9s and PDB ID: 6f0e). The docking results indicated that H-bond interactions and hydrophobic interactions were responsible for the inhibition of protein. All 15 synthesized molecules showed excellent binding energy than the standard drugs. The compounds 3a, 3b, 3e, 5a, 5b, 5e and 7a exhibited low MIC values against S. aureus whereas 3a, 3b, 5a, 5b and 7a against B. subtilis. The compounds 5a, and 5b also displayed low MIC values against P. aeruginosa. The MBC of these compounds is 2×MIC, and is equal to standard drug, Chloramphenicol. The compounds 3a, 3b, 3e, 5a, 5b, 5d and 5e showed low MIC values against A. niger whereas 3a, 5a, 5b, 7a, 7b and 7e against P. Chrysogenum. The MFC is 2×MIC and is equal to standard drug, Fluconazole. The structure-activity relationship of the compounds revealed that unsubstituted, methyl and nitro substituted compounds showed greater antimicrobial activity than those with chloro and bromo substituents. [Display omitted] [Display omitted] [ABSTRACT FROM AUTHOR]

• A series of steroidal benzo[4,5]imidazo[1,2-a]pyrimidines were synthesized using one-pot three component system. • Compounds 6 and 9 were found to have significant antifungal and antibacterial activities. • A hemolytic assay revealed that compounds 6, 8, and 9 were the least toxic to human RBCs. • A molecular docking analysis was also performed. A novel class of steroidal benzo[4,5]imidazo[1,2-a]pyrimidine derivatives was successfully synthesized via one-pot three component synthesis of pregnenolone, malononitrile, and 2-aminobenzimidazole using triethylamine as a catalyst. All the synthesized compounds were characterized by FTIR, 1H NMR, 13C NMR and mass spectra. The synthesized compounds were tested for antifungal and antibacterial activities, and strong antifungal and antibacterial activities were observed in compounds 6 and 9. The antifungal activity of the synthesized compounds was screened against C. albicans, C. glabrata, and C. tropicalis. Compound 6 exhibited a MIC of 420 μg/ml for C. albicans and C. glabrata whereas C. tropicalis showed a slightly higher MIC of 440 μg/ml. Compound 9 gave an MIC of 465 μg/ml for C. albicans , 470 µg/ml for C. glabrata while 485 μg/ml for C. tropicalis. The antibacterial activity against gram-positive (E. coli) and gram-negative (S. aureus) was investigated. Compound 6 showed MIC 12 μg/ml for E. coli and 12 μg/ml for S. aureus. While compound 9 showed MIC 6 μg/ml and 12 μg/ml for E. coli and S. aureus respectively. The hemolytic assay was also performed on human red blood cells. Compounds 6, 8 and 9 were found to be least toxic to human RBCs, showing 7.32 %, 7.27 % and 7.68 % cell inhibition at MIC, respectively. Furthermore, molecular docking analysis was carried out. [Display omitted] [ABSTRACT FROM AUTHOR]

• The sequential iodination (NIS)/trifluoromethylation (MFSDA) reactions are studied. • 1H-, 13C- and 19F-NMR are performed to assign correctly two identical CF 3 groups. • Emissions in the blue region, SS (87–201 nm) and Φ f up to 0.49 are registered. • Emissive behavior was slightly influenced by increasing water fractions (10 nm). • TD-DFT calculations have been used for predicting experimental quantum parameters. This paper presents the synthesis and photophysical characteristics of a new series of seven 5-alkyl(aryl/heteroaryl)-3,7-bis(trifluoromethyl)-2-methylpyrazolo[1,5- a ]pyrimidines (3). These compounds yielded up to 85 % through a sequential process involving iodination (N ‑bromo succinimide-NIS) followed by a trifluoromethylation (methyl fluorosulfonyldifluoroacetate [MFSDA]) reaction using 5-alkyl(aryl/heteroaryl)-7-(trifluoromethyl)-2-methylpyrazolo[1,5- a ]pyrimidines (1) as a starting point. Additionally, seven novel iodinated heterocycles, specifically 5-alkyl(aryl/heteroaryl)-7-(trifluoromethyl)-3-iodo-2-methylpyrazolo[1,5- a ]pyrimidines (2), were isolated as pure compounds with yields up to 90 % through iodination reactions of pyrazolo[1,5- a ]pyrimidines 1 using NIS. UV–Vis absorption, steady-state, and time-resolved fluorescence emission techniques revealed that compounds 3 generated emission peaks in the blue region (434–496 nm) with a Stokes shift (Δλ SS) ranging from 87 to 201 nm. However, these compounds displayed moderate to low fluorescence quantum yields (Φ f = 0.01–0.49) in comparison to the standard compound 9,10-diphenylanthracene (Φ f = 0.65) and lifetime values of 1.30–10.2 ns. Additionally, TD-DFT calculations were employed to enhance the interpretation of the studied molecules' photophysical properties. [Display omitted] [ABSTRACT FROM AUTHOR]

• Investigated P2APF ligand's effectiveness against drug-resistant Plasmodium falciparum , suggested significant results for malaria treatment in areas with limited options. • DFT investigations in various solvents highlighted solvation effects on P2APF ligand, suggesting optimal environments for reactivity. • Molecular docking revealed strong binding affinity between P2APF ligand and 5UMB chaperone protein receptor, indicating potential for targeted drug delivery against drug-resistant Plasmodium falciparum. This study aims at investigating the drug potential of p -Phenylenediamine – 2-Amino Pyrimidine – Formaldehyde terpolymer (P2APF) ligand against drug resistant Plasmodium falciparum. Plasmodium falciparum, an embodiment of cunning among malaria parasites, thrives in regions plagued by rampant mosquito transmission, subpar vector control, and limited access to effective treatments. To this end, this study explored the structural properties of the p -Phenylenediamine – 2-Amino Pyrimidine – Formaldehyde terpolymer (P2APF) ligand, (comprising p -Phenylenediamine, 2-Aminopyrimidine, and Formaldehyde) as a drug potent ligand against the common proteins coding for malaria infection. Various spectroscopic techniques such as FT-IR, UV–visible, and NMR (1H & 13C) spectroscopy were employed both experimentally and theoretically. Additionally, the ligand's surface morphology was investigated using scanning electron microscopy. To comprehend the influence of solvation, theoretical investigations utilizing density functional theory (DFT) at the B3LYPD(BJ)/6-311G++G (2d,2p) level were conducted in DMSO, water, and methanol solvents. The results from the frontier molecular orbital (FMO) analysis provided valuable insights into the electronic properties and solvation effects of P2APF. Specifically, the calculated energy gap of 3.671 eV for P2APF_methanol and 3.672 eV for P2APF_DMSO suggested these solvents as promising environments for reactivity and interactions. Molecular docking studies unveiled the most notable binding affinity between P2APF and the 5UMB chaperone protein receptor, exhibiting a binding affinity of -7.3 kcal/mol on serine and aspartic acid residues, with an average bond distance of 2.25 Å. This robust protein-ligand interaction signifies the promising potential of the P2APF ligand in targeting this specific receptor, thereby combating drug-resistant strains of Plasmodium falciparum for the present and the future. [ABSTRACT FROM AUTHOR]

• A series of diversly functionalized pyrimidine derivatives were synthesized. • The synthesized compounds were characterized by spectroscopic and analytical techniques. • They were screened for their anticancer activity against MCF-7 and HepG2 cell line. • Promising cytotoxic compounds 5a, 5c, 5 g, 5 h and 5i were tested for EGFR and HDAC inhibition studies. • Molecular docking in the EGFR, HDAC1 and HDAC6 active site confirmed the obtained activity. Pyrimidine scaffolds are an exceptional kind of heterocyclic ring that may be used to create and develop novel anticancer drugs. As a result, the current work described the design and synthesis of novel pyrimidine derivatives (5a-j) as potent dual inhibitors of epidermal growth factor receptor (EGFR) and integrating histone deacetylase (HDAC). Using elemental analysis and spectroscopic techniques, the structure of the newly synthesized compounds was elucidated. All the compounds were tested in vitro against MCF-7, HepG2 and A549 cell lines for their antiproliferative properties. Compared to the reference medication erlotinib, compounds 5 h and 5i demonstrated remarkably improved effectiveness against MCF-7, HepG2 and A549 cell lines and better safety towards normal WI-38 cells. The EGFR and HDAC inhibitory effects of compounds 5a, 5c, 5 g, 5 h, and 5i were assessed. With IC 50 values of 8.43 and 6.91 nM, respectively, the compounds 5 h and 5i demonstrated considerable inhibition against EGFR L858R/T790M mutant kinase. Compound 5i had a strong inhibitory effect compared to reference drug Vorinostat (SAHA) against the investigated isoenzymes of HDAC1, HDAC2, HDAC4, and HDAC6 with an IC 50 values of 22.73, 20.08, 3100, and 3.71 nM, respectively. Additionally, docking studies were performed to determine the binding mode of potent compounds 5 h and 5i, towards the potential target EGFR, HDAC1 and HDAC6 proteins. Furthermore, all of these results suggested that the target compounds 5 h and 5i might be seen as viable lead candidates for the dual inhibition of both EGFR and HDAC enzymes, which would enable the identification of novel anticancer agents. [Display omitted] [ABSTRACT FROM AUTHOR]

• A new series [1,2,4]triazolo[1,5 -a ]pyrimidine, or benzo[4,5]imidazo[1,2- a ]pyrimidine linked to phenoxy-N-arylacetamide were designed and synthesized. • The cytotoxicity of the new compounds was assessed in vitro against Hela, MDA-MB-231, A375, A549 cell lines. • Well diffusion method was utilized to assess the antibacterial capabilities of the synthesized compounds (11a-d and 21a-d) against different bacterial strains. • Molecular docking was performed to confirm the binding affinities of 21 towards different antibiotic-target proteins (PDB IDs: 4H8E, 4C13, 1JIJ, and 1AJ0). • The DNA binding characteristics suggesting that 21c has a good potential for DNA binding. A facile, and efficient regiochemical synthesis of 7-amino[1,2,4]triazolo[1,5- a ]pyrimidine-6-carbonitriles, or 4-aminobenzo[4,5]imidazo[1,2- a ]pyrimidine-3-carbonitriles that are linked to phenoxy- N -arylacetamide moieties has been developed. The products are formed via the conjugate additions of exo -NH 2 and ring-NH groups of the aminoazoles (3-amino[1,2,4]triazole, and 1 H -benzo[ d ]imidazol-2-amine) to the 2-(4-(2,2-dicyanovinyl)phenoxy)- N -phenylacetamide. Well diffusion method was utilized to assess the antibacterial capabilities of the synthesized compounds (11a-d and 21a-d) against different bacterial strains, and it was found that 21c was the most potent. In accordance with experimental results, the antibacterial molecular docking findings revealed that 21c has remarkable binding capabilities toward different antibiotic-target proteins (PDB IDs: 4H8E, 4C13, 1JIJ, and 1AJ0). Upon investigating the DNA binding characteristics using absorption spectroscopy, the intrinsic binding constant for compound 21c was found to be 2.64 × 104 M −1, suggesting that it has a good potential for DNA binding. [Display omitted] [ABSTRACT FROM AUTHOR]

• Design and synthesis of pyrimidine-based charge transfer probe. • Dual mode, color changing responses with fluoride and cyanide ions. • Hydrogen bonding interaction with fluoride ions. • Micchael addition reaction with cyanide ion. • Reversible binding with fluoride and irreversible interaction with cyanide. An easily scalable pyrimidine-based charge-transfer probe has been synthesized that can be utilized for simultaneous detection of both CN− and F − ions. The orange-colored solution of compound turns into yellow upon addition of F − ion, while the spiking of CN- ion leads to a colorless solution. Such color-changes have also been noticed on solid-supported materials, such as modified paper strips. Interestingly, the interaction with F- is found to be rapid as well as reversible (checked against water), while for cyanide ion, the scenario is completely opposite, the interaction is rather slow (∼10 min incubation time), and irreversible. The detailed spectroscopic investigation indicated that F −, being basic in nature, participates in the hydrogen bonding interaction. However, CN− ion, due to its highly nucleophilic character, formed Michael addition reaction product. Both these interactions substantially curtail the extent of intramolecular charge transfer and thereby resulting distinct changes in visible color. Detection of multiple anions via distinct naked-eye color changing response is not very common in the literature and therefore will be beneficial for future development of new sensory systems. [ABSTRACT FROM AUTHOR]

• Novel pyrazolo-pyrano[2,3- d ]-pyrimidine molecular hybrids were reported. • Its structure elucidation was established via different spectroscopic techniques. • Synthesized compounds were evaluated anti-diabetic activity (in vitro) against α-glucosidase and α-amylase enzymatic inhibition. • Compound 7d showed the high potency inhibitory activity for the α-glucosidase, and α-amylase. • Binding interaction was also validated with molecular docking studies. The anti-diabetic potential of newly synthesized pyrazolo-pyrano[2,3- d ]-pyrimidine analogues (7a-j) was evaluated through comparative screening against two enzymatic targets like α-glucosidase and α-amylase. All newly prepared molecules were characterized and confirmed by 1HNMR, 13CNMR, and HR-MS analysis. The in vitro anti-diabetic activity was screened using α-glucosidase and α-amylase enzymatic inhibition using Acarbose as standard. Among these, compound (7d) exhibited the most potent anti-diabetic activity IC 50 value of 1.18 µM, and 21.63 µM for the α-glucosidase, and α-amylase inhibition respectively, surpassing the IC 50 values of 3.26 µM and 32.21 µM for the reference Acarbose. The molecules' structural study revealed that the para-position electron-withdrawing (NO 2) group were crucial to the inhibitory activity. The other hybrid scaffolds 7f, 7c, and 7 h also exhibited good inhibition compared with reference. A molecular docking study were performed for all the molecules, and based on the AutoDock vina program score, and was further considered for molecular dynamics simulations. The investigation included a look at protein stability, APO-protein dynamics, and interactions. Using molecular dynamics simulations, the overall RMSD analysis of APO protein of α-amylase (PDB: 1B2Y), and α-glucosidase (PDB: 5NN8) forms showed a stable interaction and the average RMSD value is 1.93±0.18 Å and 1.62±0.17 Å. These novel pyrazolo-pyrano[2,3- d ]-pyrimidine molecular hybrids have the potential to be useful in the treatment of diabetes. [ABSTRACT FROM AUTHOR]

• Synthesis of substituted ethyl-1,2,3,4-tetrahydro-4-phenylpyrimidine-5-carboxylates. • Characterization of synthesized compounds by IR, NMR and HRMS. • Anti-tubercular activity against Mycobacterium tuberculosis (Mtb) H37Rv strain. • In-silico molecular modeling studies against DHFR enzyme and MMGBSA analysis. • MD simulations, RMSD and RMSF suggest stable complex and potent inhibitory effect. A small library of substituted ethyl-1,2,3,4-tetrahydro-4-phenylpyrimidine-5-carboxylate was designed and synthesized. All the characterized molecules were screened for their anti-tubercular activity using the H37Rv strain of Mycobacterium tuberculosis (Mtb). The compounds 5c, 5d, 5f, 5h , and 5k showed equipotent activity (MIC 3.12 µg/mL), compounds 5b, 5e, 5g , 5i, and 5j were more potent (MIC 1.6 µg/mL), whereas, 5a and 5l shown moderate activity (MIC 6.25 µg/mL). The potent inhibitory activity of screened compounds was rationalized with in-silico molecular modeling studies against the Mtb- dihydrofolate reductase (DHFR) enzyme. Compound 5i displayed a good docking score of −8.56 Kcal/mole with H-bond and hydrophobic interactions. These interactions revealed the stability of the complex which in turn determined the potent inhibitory effect. To get in-depth mechanistic insight into the inhibitory effect and to assess the stability of the ligand–protein complex, a molecular dynamics (MD) simulation study was performed. The RMSD and RMSF values obtained by the MD simulation study were 2.39 Å and 0.92 Å, respectively. The obtained values suggested that the drug–ligand complex maintained the stability over entire 100 ns run and the molecule did not fluctuate. The H-bond and hydrophobic interactions displayed in molecular docking studies were found to be retained in the MD simulation run. The obtained MD simulation values indicate that the complex was stable and rationalize the potent inhibitory effect. The drug-likeliness properties of potent compounds were calculated and the values thus obtained suggested that the molecule 5i has drug-likeliness properties and complies with Lipinski's rule of five/Ro3. Hence, the identified compounds can be taken into further stages of drug discovery processes. [Display omitted] [ABSTRACT FROM AUTHOR]

• New library of pyrimido[5,4- e ][1,2,4]triazolo[1,5- c ]pyrimidine derivatives was designed and synthesized. • All the newly synthesized compounds were screened for their herbicidal activities by Petri dish assays and pot experiments in a glasshouse. • The inhibitory efficacies of the target compounds against ALS were evaluated, and molecular docking analysis is performed. • The results of bioassay and molecular docking indicated that compound 7 2-((2,4-dichlorophenoxy)methyl)-10-(methylthio)-8-(pentylthio)-5-propyl-5,6-dihydro pyrimido[5,4- e ][1,2,4]triazolo[1,5- c ]pyrimidine showed excellent biological activities and exhibited good affinities for ALS, and could be possibly acted as a lead compound of ALS inhibitor. The development of nitrogen-containing heterocyclic compounds with novel structure and remarkable biological activity is always in demand. Herein, new library of pyrimido[5,4- e ][1,2,4]triazolo[1,5- c ]pyrimidine derivatives (1–98) was designed, synthesized, and characterized by Fourier Transform Infrared Spectoscopy (FT-IR), nuclear magnetic resonance (1H NMR), carbon-13 nuclear magnetic resonance (13C NMR), high-resolution mass spectroscopy (HRMS), and X-ray single-crystal diffraction. Their herbicidal activities were screened for the first time by Petri dish assay and pot experiment in a glasshouse. The results indicated that some of title compounds (e.g., 1, 4, 5 , and 7–11) exhibited 100 % inhibition rate against the roots and stalks of Cucumis sativus, Raphanus sativus, Sorghum bicolor and Echinochloa crusgalli at a dosage of 100 mg/L, higher than the positive control Flumetsulam, a well-known commercial acetolactate synthase (ALS) inhibiting herbicide. 2-((2,4-Dichlorophenoxy)methyl)-10-(methylthio)-8-(pentylthio)-5-propyl-5,6-dihydropyri- mido[5,4- e ][1,2,4]triazolo[1,5- c ]pyrimidine 7 showed notable postemergence herbicidal activity against Abutilon theophrasti, Amaranthus spinosus, Chenopodium album, Digitaria sanguinalis, Echinochloa crusgalli , and Setaria viridis at a rate of 375 g/ha, and its activities were similar to the positive control Flumetsulam. Enzymatic bioassays revealed that 7, 8 , and 40 displayed good inhibitory potency against ALS with 39.6 %, 39.1 %, and 40.9 % inhibition rate, respectively, comparable to that of Flumetsulam (43.5 % inhibition rate). Moreover, molecular docking analysis was conducted by using ALS protein and target ligand molecule 7. The results of molecular docking were consistent with the bioassay experiments, showing compound 7 with a new structure and excellent herbicidal potency was potent inhibitors of ALS. [Display omitted] [ABSTRACT FROM AUTHOR]

• A series of rhodamine pyrimidine derivatives (RP1,RP2,RP3 and RP4) and rhodamine pyrimidine nido-carborane derivatives (RPB1,RPB2,RPB3 and RPB4) were successfully synthesized. • Compounds RP4 and RPB4 have a good inhibitory effect on tumor cells in cytotoxicity experiments. • According to cell imaging experiments, compounds RP4 and RPB4 can enter tumor cells through the cell membrane and have good cell compatibility. Because of the advantages of fluorescent drugs consisting of fluorescent dyes and compounds with anticancer activity for therapeutic diagnostics and personalized medicine. A series of fluorescent antitumor drugs rhodamine pyrimidine derivatives (RP1, RP2, RP3 and RP4) were synthesized by linking rhodamine B and pyrimidine derivatives through ethylenediamine bridge and then introduced into nido- carborane to form fluorescent salt derivatives (RPB1, RPB2, RPB3, and RPB4). It improves the tumor targeting and imaging ability of pyrimidine derivatives. By CCK8, it was found that the inhibition rates of RP4 and RPB4 at 10 μg/mL on HeLa, PC-3 and L02 cells were 70.4 %, 68.7 %, 86.1 % and 72.5 %, 76.4 %, 81.0 %, respectively. The compound has strong inhibitory effect on cancer cells. The logP values of compounds RP4 and RPB4 were between 0 and 3, which were easily absorbed and transported through the cell membrane. Further cell imaging experiments showed that RP4 could enter tumor cells through cell membrane and had good biocompatibility. The experimental results show that compounds RP4 has good imaging capability and tumor targeting, and is a potential fluorescent anticancer agents. [Display omitted] [ABSTRACT FROM AUTHOR]

• Synthesis of novel hybrid Benzo[4,5]imidazo[1,2- a ]pyrimidine derivatives using ionic liquid (DIPEAc) as a reaction media. • In vitro antimalarial screening of synthesized Benzo[4,5]imidazo[1,2- a ]pyrimidine derivatives. • Molecular docking of active compounds at the binding site of DHFR enzyme. • 3D-QSAR analysis and In silico study of Benzo[4,5]imidazo[1,2- a ]pyrimidine derivatives. • ADMET parameter prediction of active compounds, leading to oral bioavailability evaluation. Synthesis of Benzo[4,5]imidazo[1,2- a ]pyrimidine derivatives using an environmentally friendly Biginelli-type reaction in ionic liquid DIPEAc was performed. Remarkably, this ionic liquid exhibits efficient recyclability over five cycles. Synthesized compounds underwent rigorous in vitro antimalarial efficacy screening, complemented by computational and in vitro studies, assessing their potential as Plasmodium falciparum dihydrofolate reductase (Pf -DHFR) inhibitors. A robust 3D-QSAR model was established and validated, elucidating structure-activity relationships. Estimated ADMET descriptors highlighted favorable pharmacokinetics, suggesting their role in new antimalarial drug development. This study exemplifies the synergy of sustainable synthesis, enzyme inhibition, and pharmacokinetic profiling, promising a transformative outlook for antimalarial innovation. [Display omitted] [ABSTRACT FROM AUTHOR]

• Synthesis of new cyanoacetamidopyrimidine compounds and their utility as a starting material for the synthesis of more heterocyclic compounds bearing pyrimidine moiety. • The main objective of this work was to study cytotoxicity and antitumor evaluation of the new pyrimidine derivatives. • Study the structure-activity relationship (SAR) of the newly prepared pyrimidine derivatives. • Study the molecular docking of the newly prepared pyrimidine derivatives. The precursor cyanoacetamide derivatives (6) were achieved by the reaction of pyrimidine derivative 5 with cyanoacetic acid catalyzed by acetic anhydride. The reaction of cyanoacetamide derivative 6 with different reagents afforded many heterocyclic systems such as thioacetic acid (9) , dithiolane derivatives (11) and (12) , 1,8-naphthyridine (14) , quinoline derivatives (17) and (18) , pyridine derivatives 20, 22, 24, 26 , and 27 , pyridazine (30) , pyranopyrimidine (32) , and pyrazolopyrimidine (34). All the newly synthesized compounds were characterized with spectroscopic analyses. Compounds were tested for their anticancer activity against three human cancer cell lines: hepatocellular carcinoma (HepG-2), colon cancer (HCT-116), and mammary gland breast cancer (MCF-7). The studied compound's cytotoxic activity ranged from very strong to very weak. The most active compounds were 9, 10, 11, 27 , and 34. The binding disposition of the docked compounds, in particular 9, 10, 11, 27, and 34 , towards the binding site of AKT complexed with co-crystallized ligand was investigated using molecular docking (PDB = 4EJN). A new approach for the synthesis of some new heterocyclic compounds bearing pyrimidine rings as antitumor agents. [Display omitted] [ABSTRACT FROM AUTHOR]

• Facile synthesis of a series of 22 new pyrimidine appended fused pyrazolones. • Structural confirmation by spectral data and single crystal X-ray crystallography. • Anticancer and antimicrobial testing of synthesized fused pyrazolones. • Docking studies of most active compounds 6e & 6j docked with DNA Topoisomerase 1. A series of twenty-two new pyrimidine appended fused pyrazolones 6a‒k and 7a‒k has been efficiently synthesized in good yields. Their structural characterization was achieved by physical and spectral analysis data (FTIR, NMR (1H & 13C), 2D NMR and HRMS) and single-crystal X-ray crystallography. All compounds were assayed for their in vitro anticancer activity against three human cancer cell lines viz. (i) human colorectal carcinoma (HCT116), (ii) human breast carcinoma (MCF7), and (iii) human prostate cancer (PC3) employing sulphorhodamine B assay by taking Camptothecin as a standard reference drug, and were also evaluated for their in vitro antimicrobial activities against two Gram-positive bacterial strains viz. E. faecalis (MTCC 439) and S. aureus (NDRI 110), two Gram-negative bacterial strains viz. E. coli (MTCC 723) and S. Typhi (MTCC 3224), and one fungal strain R. oryzae (MTCC 262) employing a quantitative micro-spectrophotometric assay by taking Tetracycline and Fluconazole as standard reference drugs for the antibacterial and antifungal testing, respectively. Amongst all the newly synthesized pyrazolones, 6e and 6j were found to exhibit maximal inhibitory activity against all the tested cancer cell lines, however, these are well active in comparison to the standard drug Camptothecin. The antimicrobial activity evaluation results revealed that compound 6k showed the highest potency against all the bacterial and fungal strains under study in comparison to the respective standard drugs Tetracycline and Fluconazole. Furthermore, in vitro anticancer activity was supported by docking studies performed on the derivatives 6e and 6j with their binding scores ‒65.842 and ‒64.555, respectively whereas the binding score of co-crystallized Topotecan was ‒65.675. Using X-ray crystal structure of compound 6e, DFT analysis gave energies of HOMO and LUMO as ‒0.2268 a.u.and ‒0.0872 a.u., respectively while the calculated dipole moment was 9.202833 D. The HOMO is mainly concentrated on chlorophenyl and indenopyrazolone nucleus while LUMO showed larger coefficient on dimethylpyrimidine ring which is in accord with binding interaction results of docking studies. [Display omitted] [ABSTRACT FROM AUTHOR]

• A novel series of quinazoline-pyrimidine derivatives (3a - 3i) linked to different aryl substitutions were designed and synthesized as promising anti-cancer candidates. • Compounds 3d and 3f were found to be the most active compounds against the SW480 cell line, with IC 50 = 1.1 and 8 μM, respectively. • Molecular docking, pharmacokinetic profiles, and DFT analysis were performed to investigate the interactions between ligands and EGFR targets and the drug-likeness of the synthesized compounds. • The result of MD simulation revealed that 3d ligand was stable in the active site of EGFR receptor and confirm docking study. A novel series of quinazoline-pyrimidine derivatives (3a - 3i) linked to different aryl substitutions were designed and synthesized as promising anti-cancer candidates. The Chemical structures of the new compounds were confirmed by IR, 1HNMR, 13CNMR, and Mass spectroscopy. Antiproliferative activities of all synthesized compounds were evaluated against MCF-7 and SW480 cell lines by the MTT method. The biological results exhibited IC 50 values in the range of 1.1 to 59.0 μM. Compounds 3d and 3f were found to be the most active compounds against the SW480 cell line, with IC 50 = 1.1 and 8 μM respectively. Furthermore, in silico analyses of the Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profiles of the synthesized compounds exhibited that our molecules have acceptable predictive ADMET features. The results of the docking studies were in line with biological outputs, Density functional theory (DFT) studied 3a and 3d 's reactivity descriptors at the B3LYP/6-31G** level of theory. HOMO, LUMO, and electrostatic surface potential energy were also examined. According to DFT calculations, compound 3d exhibits higher reactivity than compound 3a , which is consistent with the experimental observations. Molecular dynamic simulation of the potent synthetic compound (3d) and native ligand (Erlotinib) was performed to validate the docking study and also, RMSD, RMSF, total hydrogen bond, and clusters were analyzed. A novel series of quinazoline-pyrimidine derivatives (3a - 3i) were designed and synthesized as promising anti-cancer agents. The antiproliferative activity of all compounds was investigated against two cancerous cell lines (SW480 and MCF-7) by using an MTT assay. A docking study and MD simulation were performed to validate the biological outputs. Furthermore, in silico analysis of the ADME profile of compounds and DFT analysis was also investigated. [Display omitted] [ABSTRACT FROM AUTHOR]

• Three novel sets of pyrazolo[1,5-a]pyrimidines with expected cytotoxicity and PIM-1 and PIM-2 inhibition potential were designed and synthesized. • Three derivatives 5h, 5j, and 5l exhibited significant anticancer activity against tumor cells presenting IC 50 range of 1.26–3.22 µM. • The 4-hydroxy-3-methoxyphenyl analog 5j has shown the best cytotoxic activity combined with a lower level of toxicity towards normal cells (WI-38 cell line), suggesting an increased level of safety with high selectivity toward cancer cells. • Compound 5j displayed a potent activity against both PIM-1 and PIM-2 having IC 50 0.158 and 0.297 μM; respectively. • Compound 5j promoted apoptosis via elevating the levels of Bax, p53, and caspase-3 and dropping down Bcl-2 level. This study involved designing and synthesizing new derivatives of pyrazolo[1,5- a ]pyrimidine 5a-l, which were prepared via reaction of 4-Arylazo-1 H -pyrazole-3,5-diamines 3a,b with arylidenemalononitriles (4a-f) in refluxing methanol. The structure of the synthesized derivatives were confirmed using different spectroscopic techniques. Virtual screening was achieved for the newly designed derivatives using docking simulation between the target pyrazolo[1,5- a ]pyrimidine 5j and the active binding site of the PIM-1 enzyme. The cytotoxicity of novel derivatives of pyrazolo[1,5- a ]pyrimidine framework was screened on the cancer cell lines: colon (HCT-116), hepatocellular (Hep-G2), and breast (MCF-7). Comparing with doxorubicin, compounds 2,5-diamino-7-(4-ethoxyphenyl)-3-(p-tolyldiazenyl)pyrazolo[1,5-a]pyrimidine-6-carbonitrile; 5h, 2,5-diamino-7-(4-hydroxy-3-methoxyphenyl)-3-(p-tolyldiazenyl)pyrazolo[1,5-a]pyrimidine-6-carbonitrile; 5j, and 2,5-diamino-7-(furan-2-yl)-3-(p-tolyldiazenyl)pyrazolo[1,5-a]pyrimidine-6-carbonitrile; 5l exhibited noteworthy anticancer properties, with half maximal inhibitory concentration (IC 50 range) = 1.26–3.22 μM. In addition, the most potent compound, 5j demonstrated a lower level of toxicity towards normal cells (WI-38 cell line), suggesting an increased level of safety. Compounds 5h, 5j, and 5l were evaluated for their activity against three different PIM kinases (PIM-1, PIM-2, and PIM-3 enzymes) in an effort to elucidate their inhibitory potential on PIM kinases. Additionally, the apoptotic potency of 5j was assessed on MCF-7 cells. Results revealed that compound 5j was potent against both PIM-1 and PIM-2 having IC 50 0.158 and 0.297 μM, respectively, comparing to staurosporine's IC 50 0.294 and 0.477 μM against both enzymes, respectively, while its inhibitory activity against PIM-3 enzyme was moderate. In addition, compound 5j promoted apoptosis via elevating the levels of Bax, p53, and caspase-3 and dropping down Bcl-2 level. G1 phase arrest of cell cycle was also observed. Furthermore, docking analyses of 5j in the PIM-1 binding site was conducted. [Display omitted] [ABSTRACT FROM AUTHOR]

• 1,2,3,4-tetrazole integrated thieno[2,3-d]pyrimidine hybrids synthesis. • Evaluation of anti-microbial activities and fungal pathogens. • Binding affinities of the test molecules against selected protein targets. • Significant MIC values for the best lead compounds. The present study describes synthesis of a novel series of 1,2,3,4-tetrazole integrated thieno[2,3- d ]-pyrimidine hybrid 11a -l. Further, in vitro anti-microbial activities of the synthesized analogues 11a - l were evaluated against Gram-positive bacteria and Gram-negative bacteria, and fungal pathogens respectively. As a result, the analogues 11d and 11l were shown potent anti-bacterial activities 0.09–0.48 µg/mL and 0.07–0.51 µg/mL, respectively against tested pathogens and compared with standard Ciprofloxacin (0.08–0.34 µg/mL). As well, the compounds 11 h and 11l have also shown highest inhibition zones (ZOIs) ranging from 13.20 ± 0.57 to 16.70 ± 0.50 ; and 17.00 ± 0.00 to 17.50 ± 1.04 mm, respectively against nominated fungal pathogens. Subsequently, the conducted molecular docking studies with the active site of DNA gyrase of Staphylococcue aureus and Esterase of Aspergillus niger were shown that all the synthesized derivatives 11a - l exhibited good docking scores of between -9.2 and -8.8 kcal/mol and were better as compared with standard drugs. [Display omitted] [ABSTRACT FROM AUTHOR]

In this study, the efficiency of MIL-53(Fe) metal-organic framework (MOF) the one-pot, three-component reaction of isothiocyanate, aromatic aldehydes and 6-aminouracil and/or N,N -dimethyl-6-aminouracil to form pyrimido[4,5- d ]pyrimidine derivatives is investigated. Using this method all reactions are performed at 110 °C under solvent-free conditions with good to excellent product yields during acceptable reaction times. The other important merit of this method is simple recovery of MIL-53(Fe) through filtration which makes it reusable for further cycles without considerable decrease in its activity. The method is demonstrated to be a truly green process with sustainability and economics. Image 1 • MIL-53(Fe) was characterized by EDX, SEM, TGA, XRD and FT-IR analysis. • The attractive features of this process are high yields, short reaction times, simple workup and environmentally benign procedure. • Use of MIL-53(Fe) inthe multicomponent synthesis of triazolo[1,5- a ]pyrimidinediones. • Reusability of th catalyst. [ABSTRACT FROM AUTHOR]

• A novel series of novel Morpholino-1,3,5-triazine-pyrimidine were synthesized. • The molecules were tested for DPP-4, −8, and −9 inhibition. • Compounds selectively inhibit DPP-4, displaying compound 8c as most potent analogue. • Compound 8c was efficiently docked in the catalytic triad of DPP-4. • Compound 8c showed excellent anti-diabetic activity in high-fat low dose streptozotocin (STZ)-induced diabetes in Wistar rats. Due to their favorable safety profile, DPP-4 inhibitors are the suggested option for Type 2 Diabetes Mellitus (T2DM) for therapeutic purposes. In light of this, in this paper, we report the discovery of several novel morpholino-1,3,5-triazine-pyrimidine hybrid compounds. These compounds were synthesized via an inexpensive and simple synthetic method in high yields. The target molecules' structures have been established using FT-IR, 1H NMR, 13C NMR, mass, and elemental analyses. These compounds inhibited DPP-4 more effectively and selectively than DPP-8 and DPP-9. Compound 8c has been identified as the most effective DPP-4 inhibitor with an inhibitory concentration (IC 50) of 2.9 nM. In docking analysis, compound 8c demonstrated good glide energy, and various bonded and non-bonded interactions with key DPP-4 amino acid residues of the S1/S2 site, including Tyr666, Val656, Tyr547, Gly632, Asn710, etc. Furthermore, the effect of compound 8c was also studied on high-fat, low-dose streptozotocin (STZ)-induced diabetes in Wistar rats to determine its anti-diabetic performance. Compound 8c has been shown to considerably improve the insulin level, lipid profile, and anti-oxidant status of diabetic Wistar rats in a dose-dependent manner, with no toxicity. Our findings imply that new morpholino-pyrimidine 1,3,5-triazine hybrid compounds could serve as potential lead for anti-diabetic drug discovery. [Display omitted] [ABSTRACT FROM AUTHOR]

• Modification of the sugar nucleoside analogue. • Substitution of furanose ring with various substituted uracil and synthesis of L-Nucleosides. • The synthesized compounds are assayed by HIV-RT assay. • The docking score shows that the compounds have a good affinity towards reverse transcriptase enzyme. The remarkable activity of 1,3-thiazolidine pyrimidines against a variety of viruses has made them a viable class of antiviral medicines. These compounds exhibit a unique mechanism of action, targeting multiple stages of the viral life cycle, including viral entry, replication, and release. Moreover, their broad-spectrum antiviral activity and low cytotoxicity make them an attractive drug candidate for the treatment of viral infections. In this article, we detailed the synthesis of 1,3-thiazolidine pyrimidine derivatives substituted on the 5th position of the pyrimidine ring with different functional groups. The anti-HIV activity of the synthesized compounds was tested using the HIVRT assay. In comparison to the IC 50 value of standard nevirapine (112.2 nM), the 1,3 thiazolidine pyrimidine compound substituted with Fluoro S4 (21.16 µM) and Bromo S5 (30.52 µM) only has moderate anti-HIV activity. Similarly, compounds S5 and S4 have a high affinity for the active site of HIV-1 reverse transcriptase, as evidenced by their docking scores of -89.5147 and -82.5556 kcal/mol, respectively. [Display omitted] [ABSTRACT FROM AUTHOR]

• Novel 1,2,3-triazolo[4′,5′:3,4]pyrazolo[1,5- a ]pyrimidin-2-ium-1(3)-ides are studied. • Thermal decomposition and oxidative cyclization on diazenyl precursors are applied. • Green emission with large stokes shifts independent of solvent polarity is observed. • TD-DFT calculations are performed and redox analysis conducted by cyclic voltammetry. • Redox processes are mainly influenced by EDG/EWG effects of the aryl substituents. This study reports the unexpected synthesis of eight examples of a new heterocyclic system, which is composed of a charged triazole ring fused to the pyrazolo[1,5 -a ]pyrimidine, named 2,8-(diaryl)-6-(trifluoromethyl)-[1,2,3]triazolo[4′,5′:3,4]pyrazolo[1,5- a ]pyrimidin-2-ium-1(3)-ides (2). Compounds 2 were successfully synthesized from the reactions of E -3-(aryldiazenyl)-7-(trifluoromethyl)-pyrazolo[1,5- a ]pyrimidin-2-amines (1) in yields of up to 85% by employing two different method: thermal azide decomposition and oxidative cyclization. In general, derivatives 2a–h presented absorption bands at the ultraviolet region (250–380 nm) and green emission properties with large Stokes shifts. Moreover, TD-DFT calculations were performed, and redox analysis was conducted by cyclic voltammetry. [Display omitted] [ABSTRACT FROM AUTHOR]

• Synthesized first-in-class uracil-barbituric acid-imines using new method. • Observed anti-Tb activity in 6 compounds; compound D16 had an MIC 100 of 6 µM. • Compounds are noncytotoxic to mouse macrophage cell line at 25 µg/mL. • Conducted in silico docking to analyze mechanism of action. • D16 exhibited −9.1 kcal/mol binding affinity with TK. Two series of novel multifunctional pyrimidine–imine hybrids were synthesized and evaluated for their antitubercular and antimicrobial properties. A novel synthetic methodology utilizing water as a green solvent and a catalytic amount of HCl resulted in the isolation of barbituric acid – uracil – imine hybrids in moderate to good yields. The in vitro antitubercular activity of the compounds revealed exceptional activity, with D16 showing MIC 100 at 6 µM, which is comparable to the commercial drug ethambutol with MIC 100 at 7.63 µM. Compounds D7, D12, D18, D19 , and D20 also showed MIC 100 at concentrations ranging from 10.60 µM to 50.86 µM. The compounds were also noncytotoxic in the mouse macrophage cell line (RAW 264.7) at 25 µg/ml concentration. Molecular docking studies were carried out against M.tb thymidylate kinase to gain insights into the binding modes of the compounds and understand the plausible mechanism of action. The compound D16 outperformed all compounds with a MIC 100 of 6 µM, attributed to its strong binding affinity with thymidylate kinase valued at -9.1 kcal/mol. Compounds also showed promising activity against pathogenic bacterial and fungal strains, with the M series being more active. Even though the compounds showed broad-spectrum antibacterial activity against Gram-positive and Gram-negative bacteria, the inhibitory effect on the growth of Gram-positive bacteria was more significant. This may be due to the structural difference in the cell wall composition of both bacteria. Compound M9 displayed moderate to good activity against bacteria and various species of Candida. This is the first-ever report on the synthesis and biological evaluation of uracil–imine hybrids as antitubercular and antimicrobial agents. [Display omitted] [ABSTRACT FROM AUTHOR]

• PEG-4000-OSO 3 H catalysed microwave-assisted MCRs of spiro-chromeno[2,3- d ]pyrimidines 4a-o. • Single crystal XRD analysis of 4j shows a monoclinic system with a P 2 1 / n space group. • DFT was used to gain insight into molecular geometry and physicochemical properties. • Compounds 4j and 4k exhibit excellent potency against T-47D (breast) and WiDr (colon) cell lines. • The most potent compound is 4j , which exhibits GI 50 values in the range 5.2–11 µM against all cell lines. Herein, we established an environmentally benign green approach for the synthesis of new spirochromeno[2,3- d ]pyrimidines. PEG-4000-OSO 3 H catalysed microwave-assisted multicomponent reaction of sesamol, isatin and barbituric acid enables us to produce spirochromeno[2,3- d ]pyrimidines. This approach is notable for its eco-friendly polymer catalyst, rapid metal-free synthesis, easy workup, higher yield (88–97%), no need for column chromatographic purification and outstanding green credential parameters of the process. The use of harmless solvents, microwave process and reusability of reaction media made the present protocol sustainably effective from a green perspective. The molecular structure of 4j was confirmed by Single crystal XRD analysis and their DFT study was carried out. To gain insight into the molecule's geometry and physicochemical properties, quantum chemical density functional theory was employed at B3LYP/6–31G(d, p) basis set. Furthermore, all compounds were examined for antiproliferative activity against six solid human tumour cell lines. Compounds 4j and 4k exhibit excellent potency against T-47D (breast) and WiDr (colon) cell lines as compared to the standard drug cisplatin (CDDP). The most potent compound is 4j , which exhibits GI 50 values in the range 5.2–11 µM against all cell lines. [Display omitted] [ABSTRACT FROM AUTHOR]

• Biologically active pyridopyrimidine derivative was synthesized. • Characterization is done by various spectroscopic methods. • DFT and Molecular docking studies were performed. • ADMET analysis was done for drug likeness properties. In this work, we report an efficient synthesis of pyrimidine fused novel 4-phenyl-2-thioxo-3,4-dihydro-1H-pyrido[1,2- a ]pyrimido[4,5- d ]pyrimidin-5(2 H)-one. The chemical structure of the title compound was ascertained by spectral techniques including UV–Visible, FT-IR, 1H NMR, 13C NMR and HRMS. The molecule was further subjected to quantum chemical calculations at the level of Density Functional Theory method employing B3LYP (Becke 3-parameter, Lee-Yang-Parr) level with 6–311++ G (d,p) basis set. The computed characteristics of the molecule were investigated and interpreted comparing with the experimental values. Furthermore, Frontier Molecular Orbital (FMO) analysis was used to predict the energy properties and model the possible charge transfer within the molecule. The reactivity sites were identified by mapping the electron density into Molecular Electrostatic Potential (MEP). The stability of the molecule arising from hyper-conjugative interactions and charge delocalization were analyzed using Natural Bond Orbital (NBO) analysis. All the theoretical values were in good agreement with experimental studies. Docking studies was performed to examine binding sites of the title molecule and bioactivity scores indicated that the ligand's pharmacokinetic and pharmacological properties are sufficiently additive and shows the drug-likeness of the synthesized molecule. The study was validated by i) re-docking the N3-peptide inhibitor and superimposing them onto co-crystallized complex and ii) protein ligand complex. Molecular dynamics simulations were performed for 50 ns to assess the conformational stability and fluctuations of protein-ligand complexes during the simulation. [Display omitted] [ABSTRACT FROM AUTHOR]

• Pyrimidine Schiff bases are platelet aggregation inhibitors. • The synthesized complexes adopted varied geometries based on data obtained. • The compounds had enhanced radical scavenging potentials from antioxidant studies. • Cu-L2 had the highest binding affinity with 1WS3 from the fungus Aspergillus flevush. The amino-pyrimidine-based imine-chelators, 1-((pyrimidin-2-ylimino)methyl)naphthalene-2-ol(HL1), 2-(((2-hydroxynaphthalen-1-yl)methylene)amino)pyrimidine-4,6-diol(HL2) and 1-(((4,6-dimethylpyrimidin-2-yl)imino)methyl)naphthalen-2-ol(HL3) have been synthesized by facile reaction of 2‑hydroxyl-1-naphthaldehyde with 2-aminopyrimidine, 2-amino-4,6-dihydroxypyrimidine, and 2-amno-4,6-dimethypyrimidine respectively. The chelators were coordinated with Fe(II) sulfate and Cu(II) acetate to afford the corresponding complexes which were fully characterized. The Cu(II) complex exhibited superlative antimicrobial activity with an inhibitory growth zone reaching 26.5 mm outperforming both the chelators and the Fe(II) complexes. Thus Cu(II) complex has potential significance in new antibacterial drug designs and isolation. The impressive activity was due chelation which increased the lipophilic feature of the Cu(II) complex, thereby favouring its infiltration through the lipid layers of the bacterial membranes. However, compared to other samples, Fe-L2 has the best antifungal performance activity against Aspergillus niger, Aspergillus flevus, and Rhizopus stolonifer with inhibition zone of 29±1.4, 19±2.1 and 22±1 respectively. The C 18 H 12 N 5 O 6 antioxidant result confirmed that Cu-L2 had the highest scavenging ability (99.80%) at 200 μg/mL. Interestingly, Cu-L2 exhibited the highest antioxidant actions both in vitro and in silco evaluations, hence can serve as a potential antioxidant agent. Molecular docking determinations displayed a substantial binding affinity with the drug targets suggesting that the metallic compounds could be exploited for drugs design. [Display omitted] [ABSTRACT FROM AUTHOR]

• Two novel pyrimidine derivatives (BMPO and BBMP) were synthesized as eco-friendly corrosion inhibitors for mild steel in acidic environment. • BMPO and BBMP have outstanding corrosion inhibition effect with the inhibition efficiencies of 99.28% and 99.69%. • The adsorption of BMPO and BBMP is achieved by the bonding of N, S, and O atoms and the benzene ring to steel surface. • The modification with more benzyl groups in BBMP further improves its corrosion inhibition effect. In the pickling, oil well acidification, and other industrial processes, mild steel would suffer from severe corrosion in the acidic environment. In this work, two novel pyrimidine derivatives, 2-Benzylthio-6-methylpyrimidin-4(3 H)-one (BMPO) and 4-Benzyloxy-2-benzylthio-6-methylpyrimidine (BBMP), were synthesized through nucleophilic substitution reaction, and used as eco-friendly corrosion inhibitors for mild steel in HCl medium. The corrosion inhibition properties of BMPO and BBMP were investigated using electrochemical tests, surface analyses, and theoretical calculations. The experimental results indicate that BMPO and BBMP have superior inhibition effect, with high inhibition efficiency (99.28% and 99.69% at 0.6 mM) and good corrosion inhibition stability. Theoretical calculations reveal that the interface adsorption of BMPO and BBMP is achieved by the bonding of N, S, O atoms and the benzene ring to steel surface. The protonation of BMPO and BBMP molecules could further promote their adsorption. Compared to BMPO, the modification with more benzyl groups lowers the polarity and increases the hydrophobicity of BBMP. Then BBMP molecules could adsorb on steel surface to create a hydrophobic film with a large coverage, which accounts for the better corrosion inhibition effect of BBMP. [Display omitted] [ABSTRACT FROM AUTHOR]

• Seventeen new pyrazolo[3,4- d ]pyrimidine derivatives were designed and synthesized. • Cytotoxic activities were evaluated against A549, HepG2, MCF-7, and HCT-116. • In vitro VEGFR-2 and EGFRT790M tyrosine kinases inhibition assays were carried out for the most active derivatives. • Molecular docking studies were carried out. Seventeen new pyrazolo[3,4- d ]pyrimidine derivatives have been designed, created and tested as dual VEGFR-2 and EGFR inhibitors for their anticancer special effects against A549, HepG2, MCF-7, and HCT-116. In order to determine how the proposed chemicals might interact to the EGFR and VEGFR-2 receptors, molecular docking was used for these derivatives. The data from the docking studies and the results of the biological screening had excellent correlation. Compounds 14 and 15 displayed the best effects against HepG2, while the derivatives 10d, 15 and 18 showed the greatest anticancer activity against MCF-7. Moreover, compounds 15 and 18 exhibited the greatest anticancer effects against HCT-116 but compound 18 exhibited the greatest anticancer effect against A549. Compound 18 exhibited higher activities than Sorafenib against MCF-7, HCT116 and A549 correspondingly but lower actions versus HepG2. However, this substance showed greater effects than erlotinib against MCF-7 and HCT116 but lesser effects against A549 and HepG2 in that order. Compound 15 shown lower activities versus A549 but higher activity against HepG2, MCF-7, and HCT116 than Sorafenib and Erlotinib. Derivative 18 displayed higher effects as dual VEGFR-2 and EGFRT790M tyrosine kinases inhibitors more than both Sorafenib and Erlotinib respectively. Finally, our derivatives 10d, 15 and 18 demonstrated an excellent ADMET profile when calculated in silico. According to the results, our compounds could serve as a model for future creation, optimization, adaption, and research to create more powerful and selective dual VEGFR-2/EGFRT790M inhibitors with more anticancer potential. [Display omitted] [ABSTRACT FROM AUTHOR]

• Multicomponent reactions helps to swiftly synthesize and evaluate for activity. • This review covers synthesis of dihydropyrimidines and their biological activities. • Novel dihydropyrimidines can be potential anticancer therapeutics. • This review reports all the patented and marketed dihydropyrimidines as drugs. • This review reports future perspectives of dihydropyrimidines in drug discovery. One of the largest classes of organic molecules are dihydropyrimidines and its derivatives. They are widely used in a variety of pharmacological and industrial applications. Their biological and pharmacological activities include antihypertensive, antidiabetic, anti-inflammatory, antibacterial, antifungal, anticancer, and antiviral activities. The presence of pyrimidine and pyrimidine-containing rings in the substructures of therapeutically effective drugs has drawn considerable interest amongst the scientific fraternity. The potential therapeutic use of these heterocycles has prompted medicinal chemists to synthesize drugs that contain these heterocycles. Against this backdrop, this review examines the one-pot multicomponent reaction, that is, the Biginelli reaction and its mechanism. Also, we reviewed various synthetic approaches for the synthesis of dihydropyrimidines and their diverse pharmacological activities reported in the last two decades. We highlight different marketed drugs with dihydropyrimidine as a pharmacophore as well as patented dihydropyrimidines in the recent past. [Display omitted] [ABSTRACT FROM AUTHOR]

• Microwave irradiation is an important methodology to synthetize chemical compounds. • Chagas disease is a neglected tropical disease which is endemic in latin america. • Heterocyclic nuclei are in the structure of several biologically active compounds. • Conjugated heterocyclic compounds show photophysical properties. Pyrazole derivatives are pharmacologically important agents that possess a wide spectrum of biological activities. Thus, the optimization of their synthetic approaches is of great interest for medicinal and pharmaceutical chemistry. In this work, eleven new 7-aryl-2,3-dihydro-7 H -imidazo[1,2- c ]pyrazolo[4,3- e ]pyrimidines 1(a-k) were synthesized employing microwave irradiation conditions (150 W, 15–45 min). All compounds were completely characterized through Fourier Transform Infrared Spectroscopy (FT-IR), Nuclear Magnetic Resonance (NMR), and High-resolution Mass Spectrometry (HRMS) analyses. The in silico prediction of physicochemical properties showed that all analogs do not violate Lipinki's rule with prediction of good oral bioavailability. Analogs showed low activity against T. cruzi. Correlated experimental methods have been applied to investigate the photophysical properties of 1(a-k), describing their absorption properties in function of substituents. The molecular set exhibits a cyan emission, enabling it to investigate the basic fluorescence spectroscopy in solution. [Display omitted] [ABSTRACT FROM AUTHOR]

• A series of new pyrazolo[1,5- a ]pyrimidine derivatives were designed and synthesized. • Compounds 6a and 6b showed their best anticancer potency against MCF-7 breast cell line. • The potent compounds showed more SI values than that of sorafenib. • Compounds 6a and 6b proved to be potent EGFR/HER2 kinase inhibitors. • The experimental results were supported by the molecular docking studies. The pyrazolo[1,5- a ]pyrimidine core framework is a good starting point for the synthesis of drug-like molecules since the biological activity is determined by the kind and position of the substituents on the heterocyclic center. To develop safer and more effective anticancer medications, pyrazolopyrimidine derivatives (6a-o) were designed and developed. The structure and purity of the resulting molecules were confirmed by elemental analysis and various spectroscopic techniques. The human cancer cell lines, including HepG2 (liver), MCF-7 (breast), and HCT116 (colorectal), have been used to test the synthetic compounds' anticancer properties. The most of pyrazolopyrimidine derivatives demonstrated a cytotoxic impact, few compounds exhibit much more potent than doxorubicin and sorafenib. For HepG2, MCF7, and HCT116, respectively, the IC 50 values of compound 6b were 3.26, 3.19, and 5.01μM. To determine their selectivity indices, the potent molecules were assessed for cytotoxicity on the WI-38 cell line, a normal healthy cell line. Inhibition studies for the human epidermal growth factor receptor 2 (HER2) and the epidermal growth factor receptor (EGFR) were also carried out in an effort to determine their mode of cytotoxicity. With IC 50 values of 0.163 (EGFR), 0.116 (HER2) for compound 6a and 0.126 (EGFR), 0.083 (HER2) for compound 6b were the most effective dual EGFR/HER2 kinase inhibitors. Finally, molecular docking research showed that compounds 6a and 6b firmly binds to EGFR and HER2 via hydrogen bonding interactions, leading to irreversible dual kinase inhibition. The substances displayed favorable characteristics of drugs and might be applied as prototypes for further improvement. [Display omitted] [ABSTRACT FROM AUTHOR]

A novel derivative of pyrimidine containing the 1,2,4-triazolo[1,5-a]pyrimidine ring has been synthesized by means of a condensation reaction of 3-amino-1,2,4-triazole with 4-hyroxy-6-methyl-pyran-2-one. The resulting structure of 2-(4-vinylbenzyl)-2-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-3-(4-vinylphenyl)propanoate, C 10 H 12 N4O 2 , (3), has been characterized by X-ray single crystal diffraction (XRD) and a variety of selected spectroscopic techniques (1H NMR, 13C and IR). The geometrical parameters and spectral data of 3 were also compared with those of a DFT geometry optimization and molecular orbital calculation utilizing the B3LYP/6-31 + G(d,p) level of theory in PCM. The intermolecular contacts in 3 were then investigated by analysis of its Hirshfeld surface along with ESP maps. The antibacterial activity of 3 against Gram positive and Gram-negative microbial strains such as Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa were evaluated with results showing antibacterial activity of 3 with respect to a MIC reference. Image 1 • Synthesis of a novel derivative of 1,2,4-triazolo[1,5-a]pyrimidine derivative. • 3D molecular structure is characterized using x-Ray and spectroscopic techniques. • Good correlations are obtained between the spectra and Xx-ray data with the predicted ones. • The synthesized compound shows significant antibacterial activity. [ABSTRACT FROM AUTHOR]

Abstract The current work reports the synthesis of two new triazolopyrimidine derivatives from 3-aminotriazole and ethyl 3-phenylglycidate. The two new compounds were characterized using IR spectra, UV–vis spectra, NMR (1H and 13C), thermal analyses (TGA and DTA) and finally the structure of one was confirmed by X-ray diffraction studies. Quantum chemical calculations were also conducted to corroborate experimental findings. Highlights • Two new triazolopyrimidine derivatives have been synthesized and characterized. • The compounds are thermostable based on the TGA/DTA results. • The major intramolecular interactions in compound II is the H⋯N hydrogen bond. [ABSTRACT FROM AUTHOR]

Abstract Three new NNO tridentate Schiff bases derived from 5-bromosalicylaldehyde with 2-amino-4,6-dimethylpyrimidine, 2-amino-4-methoxy-6-methylpyrimidine and 2-amino-4-chloro-6-methylpyrimidine (HL 1 , HL 2 and HL 3 , respectively) and their complexes with Co(II), Ni(II) and Cu(II) have been prepared. These complexes were characterized by elemental analysis, 1H NMR, IR and electronic spectra, and with the aid of magnetic moment, molar conductivity and mass spectrometry. We further determined some of their size on the nanoscale. The results indicated that Schiff bases behaved as a tridentate NNO chelator that coordinates to the metal ions by azomethine nitrogen, pyrimidine nitrogen and phenolic oxygen, demonstrating 1 to 1 (metal to ligand) ratio. The measurements of conductivity revealed a nonelectrolytic nature of the complexes. Electronic absorption and viscosity were used to explore the ability of investigated complexes to bind to DNA, and the results indicated that binding occurred through intercalation. The antimicrobial activities of the considered complexes were evaluated against some types of fungi and bacteria. Metal complexes exhibited more antimicrobial activity as compared to their ligands. Interestingly, the CuL 3 showed the highest antimicrobial activity. The anticancer activity of the chelators and their metal complexes were investigated on hepatic cellular and human colon carcinoma cells (HepG-2 cell line) and (HCT-116 cell line), respectively. The metal complexes have shown promising results in preclinical testing and they have enhanced anti-proliferative activity against growth of cancer cells compared to their ligand. Moreover, the docking study of the HL 1, HL 2, HL 3 and their Co(II), Ni(II) and Cu(II) was reported. The theoretical DFT calculations were applied to verify the molecular geometry of chelators and their complexes. The geometry optimization results are in agreement with experimental observations. Graphical abstract Image 1 Highlights • New Co(II), Ni(II), Cu(II) complexes of NNO tridentate Schiff bases have been synthesized. • The compounds have been investigated via different physicochemical and spectroscopic tools. • DNA binding ability of the new complexes with DNA has been explored. • Antimicrobial activities against some strains of bacteria and fungi have been evaluated. • The new complexes have shown promising results in preclinical testing and anti-proliferative activity. [ABSTRACT FROM AUTHOR]

Abstract Because of the rapid increase in deaths due to Staphylococcus aureus (S. aureus) infection, significant resources have been invested over the past decade in new treatments. Successful therapy requires amalgam of therapies to delineate the pathogen while providing protection to the host cell. With this idea, indole-pyrimidine hybrids have been used to develop new antibacterial agents. This heterocyclic has a fundamental role in medicinal chemistry and serves as a key model for the development of various therapeutic agents including broad-spectrum antibacterial drugs. In this study, we have employed combined studies of Three-dimensional quantitative structure-activity relationship (3D-QSAR), molecular docking which are validated by in silico ADME prediction; those methods have been performed on indole-pyrimidine hybrids against S. aureus. 3D-QSAR study was applied using Comparative Molecular Field Analysis (CoMFA) with Q2 of 0.560, R2 of 0.925, and Comparative Molecular Similarity Indices Analysis (CoMSIA) with Q2 of 0.577, R2 of 0.876. The predictive ability of these models was determined using a test set of molecules that gave acceptable predictive correlation (R2 test) values 0.729 and 0.737 of CoMFA and CoMSIA respectively. Developed models and Docking methods provide guidance to design molecules with enhanced activity. Highlights • In this study, we employed combined studies of: • Three-dimensional quantitative structure-activity relationship (3D-QSAR). • Molecular docking. • Validation by in silico ADME prediction. • The methods have been performed on indole-pyrimidine hybrids against S. aureus. • This work allowed us to propose new heterocyclic molecules with a strong antibacterial activity against S. aureus. [ABSTRACT FROM AUTHOR]

Abstract Two new (4 – 5) and a known (3) derivatives of 1,2,4-triazolo [1,5-a]pyrimidine are synthesized and characterized through spectroscopic NMR, FT-IR and single crystal X-ray diffraction techniques. Along with experimental data, the predicted spectral data are obtained using density functional theory (DFT) at the B3LYP/6-31 + G (d,p) level of theory. The closest contacts between active atoms of the compounds are identified through Hirshfeld surface analysis and electrostatic potential map (EPM) studies. Relatively, good correlations were found between the experimental and predicted spectroscopic data with correlation coefficients higher than 90%. Hirshfeld surface analysis and EPM reveal that the closest interaction between the units of the compounds are between hydrogen atoms (39.6–46.3%). The antioxidant activity of 3 – 5 is evaluated using DPPH free radical scavenging and ferric reducing antioxidant power assays. Graphical abstract Image 1 Highlights • Synthesis of two new and one known derivatives of 1,2,4-triazolo [1,5-a]pyrimidine derivatives. • 3D molecular structures are characterized using X-Ray and spectroscopic methods. • DFT calculations at B3LYP allow a better reproduction of the experimental data. • The antioxidant activity is evaluated using DPPH free radical scavenging and ferric reducing antioxidant power assays. [ABSTRACT FROM AUTHOR]

Novel serious of pyrimidine scaffold benzamide derivatives ( 9 a-k ) were synthesized and characterized by IR, HRMS, and NMR. Docking study of compounds 9 g, 9 h exhibited H-bonding interacts with Met769 into ATP binding site of EGFR-TK which showed similar binding mode to Lapitinib (PDB code: 1M17). Results indicated the ability to potent and selective inhibitors of the Epidermal Growth Factor Receptor tyrosine kinase (EGFR-TK). The molecular electrostatic potential (MEP), frontier molecular orbitals (FMOs) and HOMO-LUMO energy gap of the title compounds were investigated by using the B3LYP/6-31G method. The synthesized compounds were screened for in vitro anti-inflammatory activity. [ABSTRACT FROM AUTHOR]

Immobilized NaHSO 4 on core/shell phenylene bridged Periodic mesoporous organosilica magnetic nanoparticles (γ-Fe 2 O 3 @Ph-PMO-NaHSO 4 ) as a new acidic magnetically separable nanocatalyst was successfully prepared in three steps: (i) preparation of γ-Fe 2 O 3 nanoparticles by a precipitation method, (ii) synthesis of an organic-inorganic periodic mesoporous organosilica structure with phenyl groups on the surface of γ-Fe 2 O 3 magnetic nanoparticles (MNPs) and (iii) finally adsorption of NaHSO 4 on periodic mesoporous organosilica (PMO) network. The results of N 2 adsorption-desorption isotherms, XRD and TEM showed formation of the Periodic mesoporous organosilica magnetic nanocomposite with the uniform size up to 15 nm. The efficiency of the new catalyst was evaluated in promoting the synthesis of [1,2,4]triazolo quinazolinone/pyrimidine derivatives as important biologically active compounds. Eco-friendly protocol, high yields, short reaction times, reusability of the catalyst and easy and quick isolation of the products are the main advantages of this procedure. [ABSTRACT FROM AUTHOR]

Some new pyridopyrimidinones derivatives (PPDs) namely (E)-2-(hexadecylthio)-8-(4-methoxybenzylidene)-5-(4-methoxyphenyl)-1,2,3,6,7,8-hexahydro-4H-cyclopenta[5,6] pyrido[2,3-d] pyrimidin 4 -one (Compound I) and (E)-8-(4-methoxybenzylidene)-5-(4-methoxyphenyl) -2-thioxo-1,2,3,6,7,8-hexahydro-4H-cyclopenta [5,6] pyrido [2,3-d] pyrimidin-4-one (Compound II) were synthesized and characterized by IR, 1 H-NMR, 13 C-NMR and mass spectroscopy. The inhibition behavior of these derivatives for the corrosion of API 5L X52 carbon steel in 5% sulfamic acid solutions were considered by various electrochemical methods such as potentiodynamic polarization (PP ), electrochemical impedance spectroscopy (EIS ) and electrochemical frequency modulation ( EFM ) techniques, theoretically by quantum chemical calculations by using DFT method and molecular dynamic simulation (MD) . PP curves presented that the PPDs act as mixed type inhibitors. By increasing PPDs compounds concentrations, the inhibition efficiency increases. The adsorption of PPDs follows Langmuir adsorption isotherm. Excellent agreement was established between the quantum chemical parameters and the experimental data. [ABSTRACT FROM AUTHOR]

In this research paper we report synthesis of two planar ligands, namely 1,3-dimethyl-5-(4ʹ/3ʹ-pyridylazo)-6-aminouracil: HL1 (1 ) for 4ʹ-pyridyazo- and HL2 ( 2 ) for 3ʹ-pyridyazo-group and, moreover, their nickel (II) square planar complexes ([Ni II (L1) 2 ] ( 3 ) and ([Ni II (L2) 2 ] ( 4 )). The report is also included solid and solution state structure of the compounds and study of noncovalent stacking interactions. Crystal structures of the ligands, 1 and 2 are monoclinic with alike space group P 2 1 / c and the complex 3 is also monoclinic with space group C 2/ c . The molecular electrostatic potential (MEP) analysis shows that the ligands possess both π-basic and π-acid character in the same framework over the center of the pyridine and the pyrimidine rings, respectively, favoring electrostatically enhanced π-π stacking interaction among the molecular units. Upon complexation, π-acidity of the pyrimidine ring increases, and the complex 3 exhibits lone pair (lp)-π stacking interaction involving lone pair of the pyridine N-atom and π-acid pyrimidine plane. The study evidences that the ligands exist in azo-enamine-keto tautomer in solid and hydrazone-imine-keto in solution state and get coordinated with nickel (II) via azo- N and uracil-6- N H , to form a distorted square planar complex. Electronic absorption bands/energies obtained from experimental and theoretical (TDDFT) study are indeed alike, giving reliability to the level of theory and the absorption band assignments. Moreover, the synthesized compounds containing uracil and pyridine fragments exhibit π-π/lp-π interactions with considerable energy for stabilization of their assemblies in the solid state. [ABSTRACT FROM AUTHOR]

N1 N2 bond in molecules containing 1, 2, 3-triazoles framework is weakened and readily cleaved when N1 is attached to a strong electron-withdrawing group. However, ticagrelor, a pyrimidine-fused triazole without a strong electron-withdrawing group on N1 site still went through isomerization reaction via N1 N2 bond rupture in the presence of acid to produce an impurity T3 . Its structure was precisely obtained via NMR spectral analysis, MS spectroscopy and X-ray crystallography. The optimal condition of the isomerization reaction was systematically studied. Moreover, the isomerization mechanism was investigated and it is likely that ticagrelor and its analogues go through isomerization reaction when the 4-NH group and electron-deficiency ring exist in their structures. Besides, the steric hindrance of the substituent on 4-NH has an effect on the reactivity of equilibrium. Under mimic in vivo condition, the isomerization reaction of ticagrelor also generated, indicating ticagrelor may be not stable in stomach. [ABSTRACT FROM AUTHOR]

1-(4-chloromethylbenzoyl)-3-(4, 6-di-substituted pyrimidine-2-yl)thioureas ( 1 and 2 ) have been synthesized using the reaction of 4-chloromethylbenzoyl isothiocyanate with 4-chloro-6-methoxypyrimidine-2-amine and 4, 6-di-methylpyrimidine-2-amine in dry tetrahydrofuran. The two compounds were characterized by FT-IR and FT-Raman (vibrational spectra), multinuclear ( 1 H and 13 C) NMR, single crystal X-ray diffraction, mass spectrometry and elemental analyses techniques. The reduced density gradient (RDG) function, which provides abundant visualization as a wide range of real space, was used to analysis the intramolecular non-covalent interactions. Besides, non-covalent interactions were discovered by us in title compounds, including hydrogen bonds, C H--lone pairs, O⋯S, van der Waals interactions and steric/ring closure effects. Hirshfeld surfaces and their two-dimensional fingerprint plots were performed to explain the intermolecular interactions in crystal lattice. The vibrational spectra (FT-IR and FT-Raman), as well as the NBO analysis have been studied using the B3LYP/6–311++G (d, p) level of approximation. [ABSTRACT FROM AUTHOR]

• US assisted synthesis of novel adamantane-pyrazolo[1,5- a ]pyrimidine hybrids. • Crystal analysis of adamantane-pyrazolo[1,5- a ]pyrimidine hybrid 14c. • Docking analysis of the hybrids against target 3CLpro of SARS-CoV-2. • Drug-likeness analysis of the hybrids using Swiss ADME. Multi-step synthesis of adamantyl-pyrazolo[1,5- a ]pyrimidine derivatives under ultrasound irradiation has been described adopting the technique of molecular hybridization, whereby two core bioactive units- adamantanamine and pyrazolo[1,5- a ]pyrimidine templates have been brought together into a new chemical entity. Ultrasound irradiation of N -(adamantan-1-yl)-3-amino- 1H -pyrazole-4-carboxamide with formylated active proton compounds yields the desired hybrids in good to excellent yields. The N -(adamantan-1-yl)-3-amino pyrazolo[1,5- a ]pyrimidine carboxamide derivatives were successfully identified with the help of spectral and analytical data. X-ray crystallography of ethyl 3-(adamantan-1-ylcarbamoyl)-7-methylpyrazolo[1,5- a ]pyrimidine-6-carboxylate (14c) unambiguously confirmed the formation of the desired hybrid. The results and the findings of the docking scores indicate that the active ligands 7a and 11b exhibited highest binding energies with a score of –7.33 Kcal/mol and – 8.73 Kcal/mol, respectively. The inhibition constant (KI) for ligands 7a and 11b were found to be 4.24 µM and 396.32 µM, respectively which are comparatively lower than the control favipiravir thereby conforming to the drug-likeness prediction. These compounds as such become favorable for screening as drug candidates compared to the control favipiravir with lower binding energy, lower lipophilicity range and very high KI constant. The active ligands have promising functions to inhibit and interfere with the replication and maturation of Chymotrypsin-like protease (3CLpro) of SARS-Coronavirus 2. The lower KI, high binding energy and drug-likeness efficiency of the compounds can be further developed into a potent drug molecule against the uncontrollable SARS-COV-2. [Display omitted] [ABSTRACT FROM AUTHOR]

• Chemoselective routes to new imidazo[1,2-a]pyrimidine derivatives, or regioisomeric hydrazonamide adducts. • Heterocyclic product outcome shown to be dictated by aromatic substituents in predictable manner. • Several compounds identified showing MIC values against gram+ve/–ve bacteria at sub-0.5 ug / mL. • Screening against HeLa cells identified a new imidazo[1,2-a]pyrimidine compound which an in silico target fishing analysis and modelling suggests could be targeting one or more of Tankyrase-2 (Tank-2), Cyclin-dependent kinase (CDK2) and Epidermal growth factor tyrosine kinase receptor (EGFR). Reaction of a series of hydrazonoyl chlorides with substituted aminopyrimidines afforded good selectivity in most cases leading either to formation of new imidazo[1,2-a]pyrimidine derivatives, or regioisomeric hydrazonamide adducts. The compounds were evaluated for antibacterial and anticancer activities. Screening against E. Coli, P. aeruginosa, S. aureus, S. epidermidis, B. subtilis and K. rhizophila did identify several different compound types with MIC of 0.1-0.4 mg/mL. Anticancer evaluation against a HeLa cell line identified one imidazo[1,2-a]pyrimidine lead. An in silico target fishing analysis suggest three possible high value protein targets, Tankyrase-2 (Tank-2), Cyclin-dependent kinase (CDK2) and Epidermal growth factor tyrosine kinase receptor (EGFR), with modelling fit against co-crystallized known ligands. This provides a new structural family lead for further investigation of molecular targets and potential SAR activity development. [Display omitted] [ABSTRACT FROM AUTHOR]

• The novel napthofuran-pyrimidine-traizne analogs 6(a-f) were synthesized. • Spectral analysis and DFT calculations were made. • The Anti-TB and antioxidant activities were disclosed. • Drug likeness prediction were investigated. • The molecular docking study and molecular dynamics were evaluated. Napthofuran and its fused heterocyclic derivatives evaluated with varied biological activity functional groups comprise an important class of compounds for new chemical entities. We here in reporting synthesis of new 3-(4-substituted phenyl)naphtho[1′,2′:4,5]furo[2,3- e ][1,2,4]triazolo[4,3- c ]pyrimidines 6(a-f). Structures of the newly synthesized compounds were confirmed by making use of spectroscopic techniques like IR, NMR and Mass. The DFT calculations were taken for the selected molecules using B3LYP hybrid functional with a 6–31+ G (d, p) all-electron basis set using the Gaussian 09 package. The bioactivity predictions were evaluated for the synthesized compounds. The In vitro biological activities were reported for the all compounds 6(a-f). The compound 6a showed high activity of anti-TB and antioxidant activity with at MIC 1.6 μg/ml and at percentage of inhibition (72.54±0.21) at 10μg/ml respectively. The compound 6f (73.21±0.11) showed antioxidant activity better than standard drug BHA (71.32±0.13) at 10 μg/ml. Furthermore, the docking studies for the newly synthesized molecules were carried out by Auto dock software with proteins InhA (4TZK), Cytochrome c peroxidase (2 × 08) and protease (Mpro) of SARS-CoV-2 Omicron (PDB ID: 7TOB). All the compounds showed a strong binding affinity for the docked proteins. The outcome of docking results showed that compound 6a had excellent binding energies -10.8, -9.4, and -9.0 kcal/mol with 4TZK, 2 × 08, and 7TOB respectively. Lastly, the protein stability, fluctuations of APO-Protein, protein-ligand complexes were investigated through Molecular Dynamics (MD) simulations studies using Desmond Maestro 11.3 and potential lead molecules were identified. [Display omitted] [ABSTRACT FROM AUTHOR]

• New imidazo[1, 2- a ]pyrimidine Schiff-bases derivatives have been synthesized. • Spectroscopic characterization was performed with 1H, 13C NMR, LC-MS, and FT-IR analyses. • The DFT studies, FMO, MEP, QTAIM and RDG analysis were done. • Molecular docking studies targeting the h ACE2 and the Spike, key entrance proteins of SARS-CoV-2 have been performed. • In silico ADMET and drug-likeness analysis were investigated. • This study may contribute to the ongoing efforts to develop effective treatments against SARS-CoV-2 or the upcoming variants. In the present work, a new series of imidazo[1,2- a ]pyrimidine Schiff base derivatives have been obtained using an easy and conventional synthetic route. The synthesized compounds were spectroscopically characterized using 1H, 13C NMR, LC-MS(ESI), and FT-IR techniques. Green metric calculations indicate adherence to several green chemistry principles. The energy of Frontier Molecular Orbitals (FMO), Molecular Electrostatic Potential (MEP), Quantum Theory of Atoms in Molecules (QTAIM), and Reduced Density Gradient (RDG) were determined by the Density Functional Theory (DFT) method at B3LYP/6–31 G (d, p) as the basis set. Moreover, molecular docking studies targeting the human ACE2 and the spike, key entrance proteins of the severe acute respiratory syndrome coronavirus-2 were carried out along with hACE2 natural ligand Angiotensin II, the MLN-4760 inhibitor as well as the Cannabidiolic Acid CBDA which has been demonstrated to bind to the spike protein and block cell entry. The molecular modeling results showed auspicious results in terms of binding affinity as the top-scoring compound exhibited a remarkable affinity (-9.1 and -7.3 kcal/mol) to the ACE2 and spike protein respectively compared to CBDA (-5.7 kcal/mol), the MLN-4760 inhibitor (-7.3 kcal/mol), and angiotensin II (-9.2 kcal/mol). These findings suggest that the synthesized compounds may potentially act as effective entrance inhibitors, preventing the SARS-CoV-2 infection of human cells. Furthermore, in silico, ADMET, and drug-likeness prediction expressed promising drug-like characteristics. [Display omitted] [ABSTRACT FROM AUTHOR]

• Pyrimidine compounds are important heterocyclic compounds and have important research significance in pharmaceutical chemistry and synthetic chemistry. have also been well explored for the past decades and are still under investigation. • With the development of catalytic methods, a series of synthesis methods of pyrimidine compounds have been well explored for the past decades and are still under investigation. • Start with "post-modification" and "co-synthesis" two strategies for the synthesis of homo-trisubstituted pyrimidines compounds, we have reviewed nearly 50 literatures published in the last 10 years on the synthesis methods in details. • In this review we have focused on "co-synthesis" strategy, we classified it by the number of reaction reactants constructed into a pyrimidine ring. Then we discussed the catalyst, solvent and other factors affecting the reaction, and summarized the reaction mechanism. • Through the analysis of the reaction mechanism, the existing problems of the existing reactions are pointed out, and the new methods for the synthesis of pyrimidine rings are prospected. Pyrimidine compounds are an important class of heterocyclic compounds. The excellent bioactivity of pyrimidine skeleton makes it of important research value in the treatment of diseases. Therefore, efficient synthesis of pyrimidine skeleton compounds is of great significance in the fields of synthetic chemistry and pharmaceutical chemistry. In the present research, a variety of methods for building pyrimidine rings have been reported. In this regard, we have reviewed the recent update on the synthesis methods of homo-trisubstituted pyrimidines compounds in details. Through the analysis of the reaction mechanism, the existing problems of the existing reactions are pointed out, and the new methods for the synthesis of pyrimidine rings are prospected. [Display omitted] [ABSTRACT FROM AUTHOR]

• Sixteen novel polyheterocyclic compounds were created in high yields (>80%) via three-component reaction. • The synthesized compounds showed good to high cytotoxicity against MCF-7 cancer cell line. • The products demonstrated high to excellent anti-oxidant activities. • These compounds exhibited moderate antibacterial properties only against Gram-positive bacteria. In this study, pyrano[3,2- e ]pyrazaolo[1,5- a ]pyrimidine derivatives were produced in high yields (80–89%), at room temperature, by three-component reactions involving alkyl isocyanides, dialkyl acetylenedicarboxylates, and 7‑hydroxy pyrazolo[1,5- a ]pyrimidines. Using FT-IR, 1H and 13C NMR, and mass spectral data, the structure of the synthesized compounds was identified. The created molecules were tested against cancer, bacteria, and free radicals to evaluate how effective they could be. It was determined whether or not the tested substances had any cytotoxic effects on the MCF-7 (breast cancer) and the MCF-10 (breast epithelial) cell lines. Compound 4l , in comparison to other compounds, has shown the most potent anti-cancer activity (IC 50 =19.70±0.89 µM), which is roughly as excellent as the standard medicine etoposide (IC 50 = 18.71±1.09 µM). Also, the antioxidant properties of the products were investigated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The results demonstrated that compound 4 h had the highest free radical scavenging effect (IC 50 = 12.12±0.40 µM), which was very close to the value for ascorbic acid (IC 50 = 11.85±0.30 µM), as the antioxidant standard. The Kirby-Bauer disk diffusion technique was applied to examine the bactericidal impact of the synthesized compounds. According to the findings, virtually all the compounds had a modest level of action against Gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus). [Display omitted] [ABSTRACT FROM AUTHOR]

• Synthesis, characterization of pyrimidine - Carbonitrile ligand and its metal complexes. • Mass and suggested fragmentation for the studied ABTTPC ligand. • Thermo gravimetric analysis and magnetic moment and UV–Visible spectroscopic studies of ABTTPC ligand and metal (II) complexes. • Molecular geometry optimization, atomic charges, bond lengths and bond angles of ABTTPC ligand and metal (II) complexes. • Powder X-ray diffraction pattern of ABTTPC ligand and metal (II) complexes. Elements, molar conductivity, IR, electronic absorption, magnetic susceptibility, and thermal decomposition data were used to describe single-core pyrimidine-carbonitrile complexes of the type [M(L) 2 (H 2 O) 2 ]Cl 2. (M = Co(II), Ni(II), Mn(II), Zn(II), Cu(II)and Cd(II)) and [Fe(L) 2 (H 2 O) 2 ]Cl 3. Elemental analyses, IR, 1HNMR , and mass spectral study were used to establish the identification and purity of the synthesized pyrimidine ligand (L). The DFT-B3LYP computational approach was used to conduct a theoretical analysis of (L) to support experimental findings. According to X-ray powder diffraction, the Fe(III) complex is amorphous, but the Cu(II), Co(II), Ni(II), and Mn(II) complexes also contain crystalline phases. Through molecular docking studies, it revealed good docking in the minor groove of the DNA of the Gram-negative bacteria (E. coli (3t88) and 5i39— P. aeruginosa), the Gram-positive bacteria (3ty7— S. aureus), and the fungi (C. albicans (1M78) receptors. When tested against multi-stranded microorganisms such as Gram-positive bacteria (Staphylococcus aureus and Staphylococcus mutans), Gram-negative bacteria (Escherichia coli, Klebsiella pneumonia, and Pseudomonas aeruginosa), and fungal species (Candida albicans and Aspergillusniger), the ligand and its metal complexes were found to have very good potency for their antibacterial and antifungal activity. [ABSTRACT FROM AUTHOR]

A series of cocrystals and a salt of the indole-3-acetic acid ( IAA ) and indole-3-butyric acid ( IBA ) (plant hormone) with 2-aminopyrimidine ( 2AP ), 2-amino-4,6-dimethylpyrimidine ( 2A-4,6-DMP ) and 2,4,6-triaminopyrimidine ( 2,4,6-TAP ) were successfully prepared, with an aim to explore the robustness of acid-aminopyrimidine synthon and its behaviour, with a change in the environment at 4,6 position of the pyrimidine ring. The formation of cocrystals/salt are examined on their ΔpKa values and were characterized by powder X-ray diffraction (PXRD), fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and their structures determined by single crystal X-ray diffraction (SCXRD). Additionally, Hirshfeld surface analysis was done to investigate the strength of the interactions and the overall percentage of short contacts and their impact on the overall packing. [ABSTRACT FROM AUTHOR]