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In this study, new benzothiazole–pyrimidine hybrids (5a–c, 6, 7a–f, and 8–15) were designed and synthesised. Two different functionalities on the pyrimidine moiety of lead compound 4 were subjected to a variety of chemical changes with the goal of creating various functionalities and cyclisation to further elucidate the target structures. The potency of the new molecules was tested against different tuberculosis (TB) strains. The results indicated that compounds 5c, 5b, 12, and 15 (MIC = 0.24–0.98 µg/mL) are highly active against the first-line drug-sensitive strain of Mycobacterium tuberculosis (ATCC 25177). Thereafter, the anti-tubercular activity was evaluated against the two drug-resistant TB strains; ATCC 35822 and RCMB 2674, where, many compounds exhibited good activity with MIC = 0.98–62.5 3 µg/mL and 3.9–62.5 µg/mL, respectively. Compounds 5c and 15 having the highest anti-tubercular efficiency towards sensitive strain, displayed the best activity for the resistant strains by showing the MIC = 0.98 and 1.95 µg/mL for MDR TB, and showing the MIC = 3.9 and 7.81 µg/mL for XDR TB, consecutively. Finally, molecular docking studies were performed for the two most active compounds 5c and 15 to explore their enzymatic inhibitory activities. [ABSTRACT FROM AUTHOR]

Nanotechnology-based strategies can overcome the limitations of conventional cancer therapies. Hence, novel series of pyrimidine Schiff bases (4–9) were employed in the synthesis of selenium nanoparticle forms (4NPs–9NPs). All selenium nano-sized forms exerted greater inhibitions than normal-sized compounds, far exceeding 5-fluorouracil activity. Compound 4 showed effective anti-proliferative activity against MCF-7(IC50 3.14 ± 0.04 µM), HepG-2(IC50 1.07 ± 0.03 µM), and A549(IC50 1.53 ± 0.01 µM) cell lines, while its selenium nanoform 4NPs showed excellent inhibitory effects, with efficacy increased by 96.52%, 96.45%, and 93.86%, respectively. Additionally, 4NPs outperformed 4 in selectivity against the Vero cell line by 4.5-fold. Furthermore, 4NPs exhibited strong inhibition of CDK1(IC50 0.47 ± 0.3 µM) and tubulin polymerase(IC50 0.61 ± 0.04 µM), outperforming 4 and being comparable to roscovitine (IC50 0.27 ± 0.03 µM) and combretastatin-A4(IC50 0.25 ± 0.01 µM), respectively. Moreover, both 4 and 4NPs arrested the cell cycle at G0/G1 phase and significantly forced the cells towards apoptosis. Molecular docking demonstrated that 4 and 4NPs were able to inhibit CDK1 and tubulin polymerase binding sites. [ABSTRACT FROM AUTHOR]

A group of EGFR inhibitors derived from thieno[2,3-d]pyrimidine nucleus was designed, synthesised, and examined as anti-proliferative lead compounds. MCF-7 and A549 cell lines were inhibited by 5b, the most active member. It had inhibitory partialities of 37.19 and 204.10 nM against EGFRWT and EGFRT790M, respectively. Compound 5b was 2.5 times safer against the WI-38 normal cell lines than erlotinib. Also, it demonstrated considerable potentialities for both early and late apoptosis induction in A549. Simultaneously, 5b arrested A549's growth at G1 and G2/M phases. Harmoniously, 5b upregulated the BAX and downregulated the Bcl-2 genes by 3-fold and increased the BAX/Bcl-2 ratio by 8.3-fold comparing the untreated A549 cells. Molecular docking against EGFRWT and EGFRT790M indicated the correct binding modes. Furthermore, MD simulations confirmed the precise binding of 5b against the EGFR protein over 100 ns. Finally, various computational ADMET studies were carried out and indicated high degrees of drug-likeness and safety. [ABSTRACT FROM AUTHOR]

EGFR mutations have been identified in 20,000 reported NSCLC (non-small cell lung cancer) samples, and exon 19 deletions and L858R mutations at position 21, known as "classical" mutations, account for 85–90% of the total EGFR (epidermal growth factor receptor) mutations. In this paper, two series of EGFR kinase inhibitors were designed and synthesised. Among them, compound B1 showed an IC50 value of 13 nM for kinase inhibitory activity against EGFRL858R/T790M and more than 76-fold selectivity for EGFRWT. Furthermore, in an in vitro anti-tumour activity test, compound B1 showed an effective anti-proliferation activity against H1975 cells with an IC50 value of 0.087 μΜ. We also verified the mechanism of action of compound B1 as a selective inhibitor of EGFRL858R/T790M by cell migration assay and apoptosis assay. [ABSTRACT FROM AUTHOR]

Topoisomerases II are ubiquitous enzymes with significant genotoxic effects in many critical DNA processes. Additionally, epidermal growth factor receptor (EGFR) plays pivotal role in tumour growth and angiogenesis. A novel series of naphtho[2',3':4,5]thiazolo[3,2-a]pyrimidine hybrids have been designed, synthesised and evaluated for their topo IIα/EGFR inhibitory and apoptotic inducer activities. Cytotoxicity of the synthesised hybrids was evaluated against MCF-7, A549 and HCT-116 cell lines. Of the synthesised hybrids, 6i, 6a and 6c experienced superior cytotoxic activity compared to doxorubicin and erlotinib against the tested cancer cells. The molecular mechanism of these hybrids revealed their ability to successfully inhibit topo IIα and EGFR activities in micromolar concentration and may serve as topo II catalytic inhibitor. Moreover, these hybrids significantly arrested cell cycle at G2/M phase together with increased p53, caspae-7, caspase-9 levels and Bax/Bcl-2 ratio. The synthesised hybrids showed efficient binding pattern in molecular docking study and have acceptable drug likeness characters. [ABSTRACT FROM AUTHOR]

A novel series of multifunctional pyrazolo[3,4-d]pyrimidine-based glutamate analogs (6a–l and 7a,b) have been designed and synthesized as antifolate anticancer agents. Among the tested compounds, 6i exhibited the most potent anti-proliferative activity towards NSCLC, CNS, Ovarian, Prostate, Colon, Melanoma, Breast, and Renal cancers with good to weak cytostatic activity and non-lethal actions. 6i demonstrated higher selectivity for cancer than normal cells. 6i could significantly increase the accumulation of S-phase cells during the cell cycle distribution of cancer cells with high potency in the induction of apoptosis. The results unveiled that 6i probably acts through dual inhibition of DHFR and TS enzymes (IC50 = 2.41 and 8.88 µM, correspondingly). Docking studies of 6i displayed that N1-p-bromophenyl and C3-Methyl groups participate in substantial hydrophobic interactions. The drug-likeness features inferred that 6i met the acceptance criteria of Pfizer. Taking together, 6i could be a promising prototype for further optimization as an effective anticancer drug. [ABSTRACT FROM AUTHOR]

Novel series of aminopyrimidines bearing a biologically active cyclohexenone 3a–f and oxo-selaneylidene moiety 4, besides selenadiazolopyrimidines (5a–e and 7), were synthesised using 5,6-diaminouracils as starting materials. Compound 3a exhibited strong anti-proliferative activity against three cell lines: HepG-2 (IC50 14.31 ± 0.83 µM), A-549 (IC50 30.74 ± 0.76 µM), and MCF-7 (IC50 27.14 ± 1.91 µM). Also, it was four times more selectively cytotoxic against WI-38 cell lines than doxorubicin. Furthermore, Topoisomerase II (IC50 4.48 ± 0.65 µM) and HSP90 (IC50 1.78 ± 0.11 µM) were both strongly inhibited in vitro by 3a. The cell cycle was halted at the G1-S phase, and total apoptotic cells were 65 times more than control Hep-G2 cells. Besides, it increased caspase-3 gene expression, triggering mitochondrial cell death. Molecular docking study indicated that it could bind to Topoisomerase II and HSP90 binding sites in an inhibitory mode. Its geometric properties were investigated using the density functional theory (DFT). Furthermore, compound 3a demonstrated in silico good oral bioavailability. [ABSTRACT FROM AUTHOR]

To explore the potential use of CDK inhibitors in pancreatic ductal adenocarcinoma (PDAC) therapy, a series of novel 2-((4-sulfamoylphenyl)amino)-pyrrolo[2,3-d]pyrimidine derivatives was designed, synthesised, and investigated for inhibition on both CDK kinase activity and cellular proliferation of pancreatic cancer. Most of new sulphonamide-containing derivatives demonstrated strong inhibitory activity on CDK9 and obvious anti-proliferative activity in cell culture. Moreover, two new compounds suppressed cell proliferation of multiple human pancreatic cancer cell lines. The most potent compound 2g inhibited cancer cell proliferation by blocking Rb phosphorylation and induced apoptosis via downregulation of CDK9 downstream proteins Mcl-1 and c-Myc in MIA PaCa-2 cells. CDK9 knockdown experiment suggests its anti-proliferative activity is mainly mediated by CDK9. Additionally, 2g displayed moderate tumour inhibition effect in AsPC-1 derived xenograft mice model. Altogether, this study provided a new start for further optimisation to develop potential CDK inhibitor candidates for PDAC treatment by alone or combination use. [ABSTRACT FROM AUTHOR]

New thiazolopyrimidine derivatives 2, 3a-d, 4a-c, 5, 6a-c, and 7a,b were synthesised. All prepared compounds were evaluated by MTT cytotoxicity assay against three human tumour cell lines. Compounds 3c, 3d, 4c, 6a, 6b, and 7b exhibited potent to strong anticancer activity that was nearly comparable or superior to Doxorubicin. Compounds exhibiting significant cytotoxicity were further selected to study their inhibitory activity on the Topo II enzyme. Compound 4c was the most potent Topo II inhibitor with an IC50 value of 0.23 ± 0.01 µM, which was 1.4-fold and 3.6-fold higher than the IC50 values of Etoposide and Doxorubicin. Furthermore, compound 4c showed significant cell cycle disruption and apoptosis on A549 cells compared to control cells. Molecular docking of the most active compounds illustrated proper fitting to the Topo II active site, suggesting that our designed compounds are promising candidates for the development of effective anticancer agents acting through Topo II inhibition. [ABSTRACT FROM AUTHOR]

A novel series of 12 antipyrine derivatives containing 1,3,4-oxadiazoles (4a-d), 1,3,4-thiadiazoles (6a-d), and pyrimidines (8a-d), was preparedand assessed for its potential in vitro COX-2 inhibitors. Compared to Celecoxib, compounds 4b-d and 8d were the most potent derivatives c with a half-maximal inhibitory concentration range of 53–69 nM. Considering COX-2 selectivity index, compounds 4 b and 4c were chosen among these most potent derivatives for further investigation. The in vivo ability of compounds 4 b and 4c to counteract carrageenan-induced paw edoema has been assessed and their potential underlying mechanisms have been elucidated and the results have been further validated using molecular docking simulations. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the antitumor effect of simultaneous inhibition of dihydrofolate reductase (DHFR) enzyme. We designed some novel pyrazolo[3,4-d]pyrimidines bearing different amino acid conjugates as efficient antifolate agents attributable to their structural similarity with methotrexate (MTX) and MTX-related antifolates. All compounds were tested to screen their enzymatic inhibition against DHFR compared with the reference drug MTX and for their in vitro antitumor cytotoxicity against six MTX-resistant cancer cell lines. The flow cytometry indicated that the most potent compound 7f arrested MCF-7 cells in the S-phase and induced apoptosis. Western blot for visualisation proved the ability of compound 7f to induce the expression of proapoptotic caspases and Bax proteins in MCF-7 breast cancer cell line beside its ability to diminish the expression of antiapoptotic Bcl-2 protein. Molecular modelling studies concluded that compound 7f displayed better binding energy than that of the normal ligand MTX. New pyrazolo[3,4-d]pyrimidine derivatives 7a–m which are structurally similar to the classical methotrexate (MTX) and MTX-related antifolates were synthesised as antitumor agents. Novel N-acyl amino acid compound 7f exhibited marked DHFR inhibition activity that are parralel to both the molecular docking results and cytotoxic activity. Compound 7f could induce the expression of proapoptotic caspases and Bax proteins in MCF-7 breast cancer cell line beside its ability to diminish the expression of antiapoptotic Bcl-2 protein. All prepared compounds obey Lipinski rule of five except compound 7f. [ABSTRACT FROM AUTHOR]

The pyrido[2,3‐d]pyrimidine moieties are one of the most biologically widespread heterocyclic compounds as antimicrobial, antioxidant, antitubercular, antiviral and anti‐inflammatory. Hence, we synthesized an efficient new series of 2‐thioxo‐pyrido[2,3‐d]pyrimidinone, 2‐hydrazinyl‐(quinolin‐2‐yl)pyrido[2,3‐d]pyrimidinone,N′‐(quinolin‐2‐yl)‐pyrido[2,3‐d]pyrimidine‐(formo/aceto)‐hydrazide and substituted‐(quinolin‐2‐yl)pyrido[2,3‐d][1,2,4]triazolo[4,3‐a]pyrimidinone derivatives. The characterization of new compounds was corresponded by using spectroscopic techniques, IR, NMR and Mass spectra. In vitro, all compounds were evaluated as antimicrobial activity compared with cefotaxime sodium and nystatin as the standard drug. This work deals with the exploration of the new heterocyclic compounds and medicinal diversity of quinoline‐pyrido[2,3‐d][1,2,4]triazolo[4,3‐a]pyrimidine derivatives that might pave the way for long in the discovery of therapeutic medicine for future drug design. [ABSTRACT FROM AUTHOR]

The δ isoform of class I PI3K (PI3Kδ) has been shown as a promising target for the treatment of hematologic malignancies and immune diseases. Herein, a series of pyrido[3,2‐d]pyrimidine derivatives were designed, synthesized and evaluated for the preliminary bioactivity. Compared with idelalisib, compound S5 exhibited excellent enzyme activity against PI3Kδ (IC50 = 2.82 nM) and strong antiproliferation activity against SU‐DHL‐6 cells (IC50 = 0.035 μM). Besides, S5 inhibited the phosphorylation of Akt, which is downstream of PI3Kδ, in concentration‐dependent manner. In view of the significant improvement in potency of PI3Kδ and selectivity over other PI3K isoforms, Compound S5 deserved further investigation as a promising PI3Kδ inhibitor. [ABSTRACT FROM AUTHOR]

A novel access to pyrrolo[3,4-d]pyrimidine scaffold via tandem Staudinger/intramolecular aza-Wittig reaction of 5-acyl-4-(1-azidoalkyl)-3,4-dihydropyrimidin-2(1H)-ones promoted by PPh3 was developed. Synthesis of the starting pyrimidinones involved the reaction of readily available N-[(2-azido-1-tosyl)alkyl]ureas with Na enolates of benzoylacetone or acetylacetone followed by acid-catalyzed dehydration of the resulting products without their isolation. [ABSTRACT FROM AUTHOR]

An efficient, one pot, multicomponent, L‐arginine catalyzed synthesis of thiazolo[3,2‐a]pyrimidines is described. L‐arginine is an easily available, biodegradable, inexpensive, promising bio‐organic molecule. The current strategy is the first example of amino acid promoted, green synthesis of a series of thiazolo[3,2‐a]pyrimidines via the formation of CN and CC bonds. The major advantages of the present methodology such as recyclability of catalyst, operational simplicity, easy scale‐up, wide substrate scope, easy work‐up, inexpensive, excellent yields, and high atom economy make it a distinct improvement over the prevailing strategies. [ABSTRACT FROM AUTHOR]

Nucleoside analogues are prevalent in drug design and call for more diversified structures. Bicyclo[1.1.1]pentane (BCP) structure has recently found wide applications in drug discovery. However, incorporation of BCP fragment into nucleoside analogues is hitherto unknown. Thus, from readily available BCP-containing building blocks, six new compounds, including pyrimidine nucleoside analogues, purine nucleoside analogues, and C-nucleoside analogues were prepared in 1–4 steps, generally with good yields. [ABSTRACT FROM AUTHOR]

This article discusses the synthesis of pyrido[2,3-d]pyrimidines, which are important heterocycles found in many pharmaceutically active molecules. The traditional methods for synthesizing these compounds are described, as well as the limitations of these methods. The article then presents a new catalytic system using 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ)/tert-Butyl Nitrite (TBN)/O2 for the synthesis of pyrido[2,3-d]pyrimidines. The reaction conditions and optimization are discussed, and the results show promising yields. This research provides a new and efficient method for the synthesis of pyrido[2,3-d]pyrimidines with potential bioactivities. The given document presents a table showing the results of control experiments on the reaction of uracils and 1,3-diarylpropenes. The table includes entries for different combinations of reactants and the corresponding products and yields. The experiments indicate that both TBN and O2 promote the reaction. The table provides specific details about the reactants and products, as well as the corresponding yields. This document describes a novel and efficient method for synthesizing pyrido[2,3-d]pyrimidines/thiopyrido[2,3-d]pyrimidines using easily available starting materials. The reaction involves oxidative coupling, intramolecular cyclization, [Extracted from the article]

The present study deals with a highly efficient and regioselective synthesis of 7-aryl-5-methyl- and 5-aryl-7-trifluoromethyl-2-amino-3-(4′-arylazo)-pyrazolo[1,5-a]pyrimidines via multicomponent reaction of hydrazine hydrate, 2-(arylhydrazono)malononitrile and β-diketones in presence of p-toluenesulphonic acid under solvent-free condition. The structure of the isolated products was established on the basis of NMR (1H, 13C, and 19F) and IR spectral data. The scope of the reaction was studied using various β-diketones viz., aliphatic, aromatic, heteroaromatic, and trifluoromethyl-β-diketones. The protocol has several advantages, such as mild conditions, atom economy, practical simplicity, shorter reaction times, and avoidance of multi-step procedures. Seventeen diversely substituted pyrazolo[1,5-a]pyrimidines were screened against two breast cancer cell lines, named MCF-7 and BT474, and two leukemia cell lines, named NALM-6 and SB-ALL, using the MTT cytotoxicity assay. Preliminary results reveal that compound 2-amino-5-(4-bromophenyl)-3-(4-methoxyphenylazo)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine was identified as the most effective compound against all the four cancer cell lines with 65-49% cell survival. An efficient regioselective synthesis of 7-aryl-5-methyl- and 5-aryl-7-trifluoromethyl-2-amino-3-(4′-arylazo)-pyrazolo[1,5-a]pyrimidines is developed using solvent-free sequential multicomponent reaction of hydrazine hydrate, 2-(arylhydrazono)malononitrile with unsymmetrical β-diketones. [ABSTRACT FROM AUTHOR]

The physisorption procedure and charge transfer phenomena are very important features in surface physics, it contribute to many of important applications in solid state physics. Density functional theory (DFT) with the package of Gaussian 09 at the basis set LanL2Dz, B3LYP level has been utilized to attain the geometrical nanostructure, density contour maps, infrared spectra, electrostatic potential, LUMO energy, HOMO energy, energy band gap, electron affinity, ionization potential, density of states, dipole moment and the polarizability for the geometrical nanostructures (Cu9),(Cu10), (Cu9-OTS),(Cu9-Pyrimidine). Calculations of the geometrical nanostructure (Cu10-OTS) has been accomplished at the basis set 6-31G, but the calculations of the geometrical nanostructure (Cu10- Pyrimidine) has been accomplished at basis set LanL2MB. The interactions between the tosylate (OTS) and the nanocopper surface leads to charge transfer phenomena. The interaction between pyrimidine and the nanocopper surface leads to physisortion phenomena. Charge transfer phenomena and physisorption precedures demonstrate apparently in the pictures of contour density maps. Calculations of the energy band gap of the pure geometrical nanostructure (Cu9) and (Cu10) show that the value of energy gap of those nanostructures is pioneering in the manufacture of the electronic devices. Calculations of the ionization energy and electron affinity disclosure the best geometrical nanostructure to endow the electrons in an interaction, so the calculations disclosure the best geometrical nanostructure to acquire the electrons in an interaction. Calculations of dipole moment and polarizability disclosure the largest dipole moment and the highest activity geometrical nanostructure in the research under the treatise. Physisorption procedure and charge transfer phenomena make all hybrid geometrical nanostructures have the symmetry C1 . Physisorption phenomena makes some geometrical nanostructures have anti-ferromagnetic features, but it makes other geometrical nanostructures loses the anti-ferromagnetic feature. [ABSTRACT FROM AUTHOR]

This article discusses the synthesis of pyrido[2,3-d]pyrimidines, which are important heterocycles found in many pharmaceutically active molecules. The traditional methods for synthesizing these compounds are described, as well as the limitations of these methods. The article then presents a new catalytic system using 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ)/tert-Butyl Nitrite (TBN)/O2 for the synthesis of pyrido[2,3-d]pyrimidines. The reaction conditions and optimization are discussed, and the results show promising yields. This research provides a new and efficient method for the synthesis of pyrido[2,3-d]pyrimidines with potential bioactivities. The given document presents a table showing the results of control experiments on the reaction of uracils and 1,3-diarylpropenes. The table includes entries for different combinations of reactants and the corresponding products and yields. The experiments indicate that both TBN and O2 promote the reaction. The table provides specific details about the reactants and products, as well as the corresponding yields. This document describes a novel and efficient method for synthesizing pyrido[2,3-d]pyrimidines/thiopyrido[2,3-d]pyrimidines using easily available starting materials. The reaction involves oxidative coupling, intramolecular cyclization, [Extracted from the article]

A lead aryl pyrrolidinone anilide identified using high-throughput in vivo screening was optimized for efficacy, crop safety, and weed spectrum, resulting in tetflupyrolimet. Known modes of action were ruled out through in vitro enzyme and in vivo plant-based assays. Genomic sequencing of aryl pyrrolidinone anilide-resistant Arabidopsis thaliana progeny combined with nutrient reversal experiments and metabolomic analyses confirmed that the molecular target of the chemistry was dihydroorotate dehydrogenase (DHODH), the enzyme that catalyzes the fourth step in the de novo pyrimidine biosynthesis pathway. In vitro enzymatic and biophysical assays and a cocrystal structure with purified recombinant plant DHODH further confirmed this enzyme as the target site of this class of chemistry. Like known inhibitors of other DHODH orthologs, these molecules occupy the membrane-adjacent binding site of the electron acceptor ubiquinone. Identification of a new herbicidal chemical scaffold paired with a novel mode of action, the first such finding in over three decades, represents an important leap in combatting weed resistance and feeding a growing worldwide population. [ABSTRACT FROM AUTHOR]

We present a study on a new class of Schiff bases with pyrimidine linked hydrazinyl azole backbone. These compounds were synthesized using conventional and ultrasonication methods. Our design strategy incorporated three heteroaromatic azoles and various substituents on the pyrimidine scaffold to enhance antimicrobial properties. Antibacterial and antifungal screenings were conducted against specific pathogens, and molecular docking studies supported the results. The compounds exhibited significant antimicrobial activities, particularly against K. pneumoniae, surpassing the standard drug. These Schiff bases hold promise as potential antimicrobial agents. [ABSTRACT FROM AUTHOR]

The pyrido[1,2‐a]pyrimidine scaffold has great potential for the creation of bioactive substances. Here we propose a simple, cost‐effective, efficient approach to forming this core based on a one‐pot three‐component reaction of commercially available 3‐oxo esters, α,β‐unsaturated aldehydes and 1,3‐diaminopropane. The developed strategy makes it possible to obtain diverse pyrido[1,2‐a]pyrimidines thanks to alternative intramolecular cyclization pathways that depend on the substituent in the 3‐oxo ester. Their diastereomeric structure was determined using NMR spectroscopy and XRD. A mechanism for the formation of new pyrido[1,2‐a]pyridines has been proposed. [ABSTRACT FROM AUTHOR]

Quinazoline derivatives, as an important category of heterocyclic compounds, have received much attention for the design and development of new drugs due to their various pharmacological properties. Besides, there is a great deal of evidence showing pyrimidine analogs as anticancer agents. Thus, in the present study, for the design of new target compounds with cytotoxic activity, we focused on various quinazolinone and pyrimidine hybrids. A new series of quinazoline-pyrimidine hybrid derivatives (6a-6n) have been designed and synthesized as novel antiproliferative agents. All the synthesized compounds characterized based on their IR, NMR and Mass spectroscopic data. Antiproliferative activities of the new compounds were evaluated against three human cancer cell lines (MCF-7, A549, SW-480). The compounds were found to have appropriate potential with IC50 values ranging from 2.3 ± 5.91 to 176.5 ± 0.7 μM against the tested cell lines. Compound 6n exerted the highest antiproliferative activity with IC50 values of 5.9 ± 1.69 μM, 2.3 ± 5.91 μM and 5.65 ± 2.33 μM against A549, SW-480 and MCF-7 respectively. The results indicated that 6n could induce apoptosis in A549 cell line in a dose dependent manner and arrest in the S phase of cell cycle. Docking studies were also done to investigate the detailed binding pattern of the synthesized compounds against EGFR. Furthermore, molecular dynamic simulation and binding free energy calculation have been done to rescore initial docking pose of the synthesized compounds using ensemble-based MMGB/PBSA free energy method. According to the results, free energy calculation confirmed biological activity of compounds and also, Arg 817 and Lys 721 residues had the pivotal role in the high potency of 6n. Finally, the drug likeness and in silico ADME study were also predicted. [ABSTRACT FROM AUTHOR]

Utilizing the Knoevenagel–Michael tandem cyclocondensation reaction of barbituric acid/1,3-dimethylbarbituric acid, malononitrile, and aryl aldehydes, a sustainable methodology for the photosynthesis of pyrano[2,3-d]pyrimidine scaffolds has been devised. The present study expounds on the development of a green radical synthetic approach toward this class of compounds. In this study, a novel halogenated dicyanobenzene-based photosensitizer was utilized in an aqueous solution, exposed to air at room temperature, and activated by a blue LED as a renewable energy source for the purpose of generating energy. The primary aim of this endeavor is to employ a recently developed, easily obtainable, and affordably priced halogenated cyanoarene-based donor–acceptor (D–A). The 3DPAFIPN [2,4,6-tris(diphenylamino)-5-fluoroisophthalonitrile]} photocatalyst, as a thermally activated delayed fluorescence (TADF), is capable of inducing single electron transfer (SET) upon irradiation with visible light, thereby offering a facile and efficient approach with a high degree of effectiveness, energy efficiency, and eco-friendliness. The aforementioned phenomenon facilitates the exploration of the temporal changes that have occurred in the interactions between the surroundings and chemical constituents. The present study aimed to investigate the turnover number (TON) and turnover frequency (TOF) for pyrano[2,3-d]pyrimidine scaffolds. Additionally, it has been demonstrated that gram-scale cyclization is a viable method for utilization in industrial applications. [ABSTRACT FROM AUTHOR]

HRMS-ESI: I m i / I z i [M + H] SP + sp calcd for C SB 11 sb H SB 7 sb Cl SB 2 sb N SB 2 sb O SB 3 sb : 284.9834; found: 284.9835. I Due to long relaxation time of the hydroxypyrimidine ring (when R SP 1 sp /R SP 3 sp = Me or R SP 1 sp /R SP 3 sp = H), some quaternary carbon signals may be broadened or even may not be responsive in SP 13 sp C NMR analysis. Keywords: isoxazoles; N-O bond cleavage; hydroxypyrimidines; molybdenum; one-pot; -amino enones; 1,3-diketones EN isoxazoles N-O bond cleavage hydroxypyrimidines molybdenum one-pot -amino enones 1,3-diketones 3841 3850 10 11/01/23 20231116 NES 231116 Graph Nitrogen-based heterocycles are one of the privileged core structural motifs in organic chemistry. HRMS-ESI: I m i / I z i [M + H] SP + sp calcd for C SB 10 sb H SB 6 sb ClF SB 3 sb N SB 3 sb O: 276.0151; found: 276.0157. [Extracted from the article]

In Arabidopsis seedlings, inhibition of aspartate transcarbamoylase (ATC) and de novo pyrimidine synthesis resulted in pyrimidine starvation and developmental arrest a few days after germination. Synthesis of pyrimidine nucleotides by salvaging of exogenous uridine (Urd) restored normal seedling growth and development. We used this experimental system and transcriptional profiling to investigate genome-wide responses to changes in pyrimidine availability. Gene expression changes at different times after Urd supplementation of pyrimidine-starved seedlings were mapped to major pathways of nucleotide metabolism, in order to better understand potential coordination of pathway activities, at the level of transcription. Repression of de novo synthesis genes and induction of intracellular and extracellular salvaging genes were early and sustained responses to pyrimidine limitation. Since de novo synthesis is energetically more costly than salvaging, this may reflect a reduced energy status of the seedlings, as has been shown in recent studies for seedlings growing under pyrimidine limitation. The unexpected induction of pyrimidine catabolism genes under pyrimidine starvation may result from induction of nucleoside hydrolase NSH1 and repression of genes in the plastid salvaging pathway, diverting uracil (Ura) to catabolism. Identification of pyrimidine-responsive transcription factors with enriched binding sites in highly coexpressed genes of nucleotide metabolism and modeling of potential transcription regulatory networks provided new insights into possible transcriptional control of key enzymes and transporters that regulate nucleotide homeostasis in plants. [ABSTRACT FROM AUTHOR]

We report herein an unprecedented synthesis of difluoromethoxylated nitrogen‐containing heterocycles from the corresponding α‐(difluoromethoxy)ketones as versatile building blocks. Pyrazoles, isoxazoles and pyrimidines could be obtained via an enaminone intermediate, whereas in the direct reaction of α‐(difluoromethoxy)ketones with arylhydrazines, a Fischer indole synthesis was achieved. All these scaffolds, which are uncommon, or even sometimes novel, due to the directly attached emerging fluorinated group (EFG) −OCF2H, might be of high potential in life sciences and appear as an interesting alternative to more and more controversial classical fluorinated groups, such as the ubiquitous trifluoromethyl group. [ABSTRACT FROM AUTHOR]

Brønsted acid‐mediated intramolecular cyclization of 2‐amidoazulene derivatives, prepared by the reaction of 1‐cyano‐2‐aminoazulene derivatives with perfluoroalkyl acid anhydrides, resulted in the formation of 2‐perfluoroalkylazuleno[2,1‐d]pyrimidin‐4(3H)‐ones. Heating of these products in phosphoryl chloride led to 4‐chloro‐2‐perfluoroalkylazuleno[2,1‐d]pyrimidines. We also evaluated the reactivity of these pyrimidin‐4(3H)‐ones and pyrimidine derivatives toward the electrophilic and nucleophilic substitution reactions, revealing that a variety of functional groups can be incorporated into these derivatives. The NMR studies, NICS calculations, and single‐crystal X‐ray structure analyses revealed structural features including the bond‐length alternation of the azuleno[2,1‐d]pyrimidin‐4(3H)‐ones and pyrimidine derivatives. [ABSTRACT FROM AUTHOR]

The 3 : 1 reaction of [Cu(C2H4)n]ClO4 with 2,4-bis(2-pyridyl)pyrimidine (bpprd) in Me2CO under C2H4 afforded yellow prism crystals of the dinuclear Cu(I)–C2H4 complex [Cu2(bpprd)(η2-C2H4)2(ClO4)2] (1). The 3 : 1 reaction of [Cu(C2H4)n]NO3 with bpprd in Me2CO under C2H4 afforded yellow plate crystals of the tetranuclear Cu(I)–C2H4 complex [Cu4(bpprd)2(η2-C2H4)4(μ-NO3)2](NO3)2 (2). The 10 : 1 reaction of [Cu(C2H4)n]BF4 with bpprd in Me2CO under C2H4 afforded yellow plate crystals of the dinuclear Cu(I)–C2H4 complex [Cu2(bpprd)(η2-C2H4)2(BF4)]BF4 (3). The 3 : 1 reaction of [Cu(C2H4)n]BF4 with bpprd in Me2CO under C2H4 afforded red prism crystals of the polymeric Cu(I)–C2H4 complex {[Cu6(bpprd)4(η2-C2H4)2(μ–η2:η2-C2H4)(μ-BF4)2](BF4)4}n (4). The X-ray crystal structures of complexes 1–4 have been determined. The structural diversity of Cu(I)–C2H4 complexes bridged by bpprd with different anions was demonstrated. The 1D Cu(I)–bpprd/C2H4 coordination polymer 4 bridged by unusual μ–η2:η2-C2H4 and the μ-BF4− anion is of particular significance. Complex 1 exhibited relatively well-resolved 1H NMR signals of bpprd and C2H4 (δ = 4.97 ppm) in (CD3)2CO at 23 °C. [ABSTRACT FROM AUTHOR]

The effective methods for obtaining Fe3O4/CeO2, Fe3O4(TEOS)CeO2 nanocomposites with cerium dioxide content from 38 to 82% and from 32 to 70%, respectively were developed, their morphological, structural and magnetic studies were carried out. Cerium dioxide and magnetite composites have a crystalline structure and ferromagnetic properties characteristic for magnetite with non-magnetic impurities. Thereby it can be easily separated from the reaction medium by means of a permanent magnet. The nanocomposites exhibit catalytic activity in cyclocondensation reactions: the interaction of chalcones with acetoacetic ester in an alkaline medium in the presence of the 1.6 wt % resulting nanocomposite leads to the formation of m-terphenyl derivatives in one-stage reaction, and in the condensation reaction with the formation of the 4,6-dimethyl-N-(4-methyl-3-nitrophenyl)pyrimidine-2-amine and 4,6-dimethyl-N-(2-methyl-5-nitrophenyl)pyrimidine-2-amine, the yield of the target product was increased to 52 and 96.8%, respectively. The resulting composites can be used repeatedly, providing sufficiently high yields of the target product. [ABSTRACT FROM AUTHOR]

A novel family of 3-chloro-4-benzylidene-1-(pyrimidin-2-yl) azetidin-2-one 5a-o has been developed because antimicrobial resistance (AMR) poses a significant concern to global public health and has made it exceedingly difficult to effectively manage infectious diseases that have been connected to it. The structures of the relevant compounds have been determined and verified using spectral methods. As substances are tested against gram-positive and gram-negative strains of bacteria and fungi, results must be compared to those of conventional drugs. Products with chloro substituents in both the pposition and the m-position demonstrate good activity against the fungi Aspergillus niger and Fusarium javanicum, while those with nitro, methyl, and bromo substituents in the benzene ring's p-position, as well as those with the nitro group at the ring's m-position, demonstrate excellent activitiy against bacterial strains. [ABSTRACT FROM AUTHOR]

CDK2 is a key player in cell cycle processes. It has a crucial role in the progression of various cancers. Hepatocellular carcinoma (HCC) and colorectal cancer (CRC) are two common cancers that affect humans worldwide. The available therapeutic options suffer from many drawbacks including high toxicity and decreased specificity. Therefore, there is a need for more effective and safer therapeutic agents. A series of new pyrazolo[3,4-d]pyrimidine analogs was designed, synthesized, and evaluated as anticancer agents against the CRC and HCC cells, HCT116, and HepG2, respectively. Pyrazolo[3,4-d]pyrimidinone derivatives bearing N5-2-(4-halophenyl) acetamide substituents were identified as the most potent amongst evaluated compounds. Further evaluation of CDK2 kinase inhibition of two potential cytotoxic compounds 4a and 4b confirmed their CDK2 inhibitory activity. Compound 4a was more potent than the reference roscovitine regarding the CDK2 inhibitory activity (IC50 values: 0.21 and 0.25 µM, respectively). In silico molecular docking provided insights into the molecular interactions of compounds 4a and 4b with important amino acids within the ATP-binding site of CDK2 (Ile10, Leu83, and Leu134). Overall, compounds 4a and 4b were identified as interesting CDK2 inhibitors eliciting antiproliferative activity against the CRC and HCC cells, HCT116 and HepG2, respectively, for future further investigations and development. [ABSTRACT FROM AUTHOR]

Estradiol methyl ether (EDME) has recently been described by us as a very potent and subtype-specific inhibitor of the lysosomal cation channel TRPML1. Following the principle of bioisosteres, we worked out efficient synthetic approaches to ring-A aza-analogs of EDME, namely a methoxypyridine and a methoxypyrimidine analog. Both target compounds were obtained in good overall yields in six and eight steps starting from 19-nortestosterone via the oxidative cleavage of ring A followed over several intermediates and with the use of well-selected protective groups by re-cyclization to provide the desired hetero-analogs. The methoxypyridine analog largely retained its TRPML1-inhibitory activity, whereas the methoxypyrimidine analog significantly lost activity. [ABSTRACT FROM AUTHOR]

Natural products are a main source of new chemical entities for use in drug and pesticide discovery. In order to discover lead compounds with high herbicidal activity, a series of new pyrido[2,3-d] pyrimidine derivatives were designed and synthesized using 2-chloronicotinic acid as the starting material. Their structures were characterized with 1H NMR, 13C NMR and HRMS, and the herbicidal activities against dicotyledonous lettuce (Lactuca sativa), field mustard (Brassica campestris), monocotyledonous bentgrass (Agrostis stolonifera) and wheat (Triticum aestivum) were determined. The results indicated that most of the pyrido[2,3-d] pyrimidine derivatives had no marked inhibitory effect on lettuce at 1 mM. However, most of the pyrido[2,3-d] pyrimidine derivatives possessed good activity against bentgrass at 1 mM. Among them, the most active compound, 3-methyl-1-(2,3,4-trifluorophenyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (2o), was as active as the positive controls, the commercial herbicides clomazone and flumioxazin. Molecular simulation was performed with molecular docking and DFT calculations. The docking studies provided strong evidence that 2o acts as an herbicide by inhibition of protoporphyrinogen oxidase. However, the physiological results indicate that it does not act on this target in vivo, implying that it could be metabolically converted to a compound with a different molecular target. [ABSTRACT FROM AUTHOR]

We have designed and synthesized a new series of amide derivatives of thiazolo[5,4-d]pyrimidines (10a-j) and their structures were characterized by 1H NMR, 13C NMR and mass spectral data. Furthermore, all compounds were evaluated for in vitro cytotoxicity effects against four human cancer cell lines such as PC3 (prostate cancer), A549 (lung cancer), MCF-7 (breast cancer) and DU-145 (prostate cancer) by employing MTT assay. The cytotoxicity effects of the amide derivatives (10a-j) were compared with etoposide utilized as the positive control. Among them, five compounds 10a, 10b, 10c, 10h and 10j possessed significant cytotoxicity properties as compared with etoposide. [ABSTRACT FROM AUTHOR]

A novel heterocyclic compounds containing pyrimido[4,5-d]pyrimidine (IIIa–IIIb) and (IVa–IVb), pyrazolo[3,4-d]pyrimidine (Va'–Ve') and (VIa'–VIe'), and pyrimido[4,5-b]quinoline (VIIa'–VIIe') and (VIIIa'–VIIIe') were designed and synthesized from the starting materials, 5-(bis(methylthio)methylene)-1,3-diphenylpyrimidine-2,4,6(1H,3H,5H)-trione (IIa) and 5-(bis(methylthio)methylene)-1,3-diphenyl-2-thioxodihydropyrimidine-4,6(1H,5H)-dione (IIb) as efficient α,α-ketene dithioacetals is reported. The synthetic approaches of these types of compounds will provide an innovative molecular framework to the designing of new active heterocyclic compounds. In our study, we also present optimization of the method for synthesis along with antimicrobial evaluation of these newly synthesized compounds as antibacterial agents against the bacterial strains, like E. coli, B. subtilis, S. aureus, and P. aeruginosa also as antifungal agents against B. cinerea, C. arachidicola, A. solani, G. zeae, S. sclerotiorum, and R. cerealis. Preliminary bioassay showed that most of them exhibited certain-to-excellent antibacterial and antifungal activity. Among all the evaluated compounds, it was found that the synthesized compounds (IVb) and (VIIIc') showed the outstanding antibacterial activity (100%) against the strains E coli and S. aureus respectively comparable to the standard drug Ciprofloxacin at the same concenteration while the others exhibited better antifungal activity at 100 µg/mL. The outstanding antifungal activity (>90%) comparable to the positive controls trifloxystrobin and azoxystrobin exhibited by (VIIIc') against B. cinerea, (IVb) and (Vc') against A. solani, (IVb) against S. sclerotiorum alongwith compounds (VIb'–VIc') against R. cerealis. The structures of all the new synthesized compounds were elucidated by elemental analysis, IR, 1H NMR, and 13C NMR. [ABSTRACT FROM AUTHOR]

A series of fifteen 2-substituted-3-(4-(pyridin-2-yl)-6-(1H-pyrrolo[2,3-b]pyridin-4-yl)pyrimidin-2-yl)thiazolidin-4-one, was prepared and characterized using analytical techniques like FT-IR, NMR (1H and 13C), and mass spectrophotometry. On screening, the compounds for antibacterial and antifungal potential, the findings portrayed to be the potent inhibitor of bacterial and fungal strains. The cytotoxicity of the prepared molecules was checked against HepG2 cells to calculate the percent viable cells, which was observed to be in the range of 70–81% up to 100 µM. The molecular docking assay was performed to assess the binding modes, the extent of the H-bond, and binding affinities against the receptor glucosamine-6-phosphatase (GlcN-6P) and lanosterol 14-α-demethylase. The findings portrayed that TYR312, SER316, GLU396, LEU 448, SER303, GLY398, and SER401 were the only amino acids of GlcN-6P that formed the H-bond with the prepared molecules. Similarly, the residues GLC5, GLC6, GLC7, SER60, TYR63, THR104, ASP229, LEU230, SER249, SER251, THR485 were the only amino acids of lanosterol 14-α-demethylase) that formed H-bond with the prepared molecules. The binding affinities for both receptors were found to be in the range of –8.5 to –6.3 kcal/mole (GlcN-6P), and –8.4 to –6.8 kcal/mole (lanosterol 14-α-demethylase). [ABSTRACT FROM AUTHOR]

Hypercytokinemia, or cytokine storm, often complicates the treatment of viral and bacterial infections, including COVID-19, leading to the risk of thrombosis. However, the use of currently available direct anticoagulants for the treatment of COVID-19 patients is limited due to safety reasons. Therefore, the development of new anticoagulants remains an urgent task for organic and medicinal chemistry. At the same time, new drugs that combine anticoagulant properties with antiviral or antidiabetic activity could be helpfull in the treatment of COVID-19 patients, especially those suffering from such concomitant diseases as arterial hypertension or diabetes. We have synthesized a number of novel substituted azoloazines, some of which have previously been identified as compounds with pronounced antiviral, antibacterial, antidiabetic, antiaggregant, and anticoagulant activity. Two compounds from the family of 1,2,4-triazolo[1,5-a]pyrimidines have demonstrated anticoagulant activity at a level exceeding or at least comparable with that of dabigatran etexilate as the reference compound. 7,5-Di(2-thienyl)-4,5-dihydro-[1,2,4]triazolo[1,5-a]pyrimidine has shown the highest ability to prolong the thrombin time, surpassing this reference drug by 2.2 times. This compound has also exhibited anticoagulant activity associated with the inhibition of thrombin (factor IIa). Moreover, the anticoagulant effect of this substance becomes enhanced under the conditions of a systemic inflammatory reaction. [ABSTRACT FROM AUTHOR]

The quantum chemical simulation of complexes of the glycyl-L-glutamic acid anion and the - alanyl-L-tyrosine Ala-L-Tyr zwitterion with nucleic bases (uracyl and cytosine) is performed using the DFT/B97D method. The most energetically favorable configurations of the complexes are found. Changes in the peptide structure during the formation of the complexes are analyzed. It is shown that the complexes are stabilized by intermolecular hydrogen bonds. The stacking effect competing with the hydrogen bonding in the orientation of peptide ions in the complex is described. The topological analysis is carried out within which bond critical points and their parameters are studied and hydrogen bond energies are found in the complexes. [ABSTRACT FROM AUTHOR]

Pyrimidine annulated five‐membered heterocyclic scaffolds containing oxygen as furopyrimidine, particularly furo[2,3‐d]pyrimidine derivatives are an important class of heterocyclic compounds in pharmaceutical discovery research. Furo[2,3‐d]pyrimidines are generally synthesized either from a pyrimidine derivative by constructing a furan ring on the parent pyrimidine ring or from a suitably functionalized furan ring by generating the pyrimidine ring on the parent furan ring. Moreover, there is a wide range of multicomponent reactions that include barbituric acids as starting material for the synthesis of these compounds. Also, the reaction of barbituric acids with alkenes, alkynes, aldehydes, ketones, ninhydrin, and chloroacetylchloride, and Cloke–Wilson rearrangement of spirocyclopropyl barbiturates afforded furo[2,3‐d]pyrimidine derivatives. This review is an attempt to compile the literature of various synthetic procedures toward barbituric acids‐based furo[2,3‐d]pyrimidine and spirofuro[2,3‐d]pyrimidines. [ABSTRACT FROM AUTHOR]

This study provides straightforward synthesis of 4H-pyran-annulated heterocycles that serve as drug-like candidates for biological purposes. It was found that these multicomponent reactions performed under green conditions in the presence of sodium benzoate as an efficient, environmentally benign, and commercially available organo-salt catalyst. The target 2-amino-4-aryl-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitriles, 7-amino-5-aryl-2,4-dioxo/(4-oxo-2-thioxo)-1,3,4,5-tetrahydro-2H-pyrano[2,3-d]pyrimidine-6-carbonitriles, and 2-amino-4-aryl-5-oxo-4,5-dihydropyrano[3,2-c]chromene-3-carbonitriles, which are estimated to be important in organic synthetic and medicinal chemistry, were obtained in high yields and relatively shorter reaction times through a simple filtration. The method is versatile and amenable to many substrates, as it requires no specialized devices such as microwave, ultrasound and ball-milling. The aim of the work is the synthesis of pyran-annulated compounds in the presence of sodium benzoate as the organo-catalyst. This procedure has several further advantages, such as isolation of heterocyclic products without column chromatography or other chromatographic methods, atom-economy, step-economy, and clean reaction profiles. [ABSTRACT FROM AUTHOR]

The chemical reactivity of 2-methylchromone-3-carbonitrile (1) was investigated toward a diversity of active methylene nucleophiles. Ring-opening followed by recyclization reactions of compound 1 with some active methylene nitriles afforded 2-amino-3-substituted-4-methylchromeno[2,3-b]pyridin-5-ones. Also, reactions of carbonitrile 1 with some active methylene ketones produced 2,4-dimethylchromeno [2,3-b]pyridin-5-ones. Annulated chromeno[2,3-b]pyrazolo[4,3-e]pyridine, chromeno[2,3-b][1,3]thiazolo[5,4-e]pyridine and chromeno[2,3-b]quinoline were efficiently synthesized from reaction of carbonitrile 1 with some cyclic methylene compounds. Heteroannulated chromeno[3′,2′:5,6]pyrido[2,3-d]pyrimidines and chromeno[2,3-b][1,8]naphthyridines were synthesized from reaction of compound 2 with formic acid, formamide, and malononitrile, cyanoacetamide, respectively. Chromeno[2′,3′:6,5]pyrido[2,3-b][1,8]naphthyridine 17 was synthesized from reaction of compound 2 with malononitrile dimer. Structures of the newly synthesized products were deduced based on their analytical and spectral data. [ABSTRACT FROM AUTHOR]

Keywords: photocatalyst-free; C-H selenylation; pyrazolo[1,5- a ]pyrimidine; persulfate; visible light EN photocatalyst-free C-H selenylation pyrazolo[1,5- a ]pyrimidine persulfate visible light 3693 3699 7 10/19/23 20231102 NES 231102 Graph Pyrazolo[1,5- I a i ]pyrimidine derivatives, an important class of fused heterocycles exhibit various biological activities like antiviral, antifungal, anti-inflammatory, antibacterial, antiobesity, etc. [1] A number of commercially available agrochemicals and pharmaceuticals such as indiplon, lorediplon and zaleplon (hypnotic), ocinaplon (anxiolytic), reversan (anticancer), pyrazophos (fungicide), etc. contain pyrazolo[1,5- I a i ]pyrimidine as the core structure (Figure 1). The screening of other persulfates like Na SB 2 sb S SB 2 sb O SB 8 sb and K SB 2 sb S SB 2 sb O SB 8 sb as well as oxidants like PIDA, TBHP, and oxygen revealed that K SB 2 sb S SB 2 sb O SB 8 sb was the most efficient for this transformation (entries 2-6). Under the optimized reaction conditions, 2-methyl-5,7-diphenylpyrazolo[1,5- I a i ]pyrimidine, 2,5,7-tri-methylpyrazolo[1,5- I a i ]pyrimidine, and 2,7-diphenyl pyrazolo[1,5- I a i ]pyrimidine afforded the C3-selenylated product B 3l b , B 3m b , and B 3n b in 77, 70 and 79% yield, respectively. Selenylation of Pyrazolo[1,5- a ]pyrimidines; General Procedure In an oven-dried reaction vial containing B 1 b (0.2 mmol) and B 2 b (0.12 mmol) DMSO (1 mL) was added followed by K SB 2 sb S SB 2 sb O SB 8 sb (0.065 g, 1.2 equiv.). [Extracted from the article]

Triazolopyrimidines are emerging as potential anticancer agents. Herein, we report a novel one‐pot four component synthesis of 2‐((2‐oxo‐2‐phenylethyl/benzyl)thio)‐10‐phenyl‐4,10‐dihydro‐9H‐indeno[1,2‐d][1,2,4]‐Triazolo[1,5‐a]pyrimidin‐9‐ones by the reaction of 1,3‐indanedione, aromatic aldehyde, 5‐amino‐4H‐1,2,4‐Triazol‐3‐thiol and phenacyl bromide in acetic acid with piperidine as catalyst at 90 °C for 13 hours. All the final compounds were identified on the basis of their FT‐IR, 1H NMR, 13C NMR and HRMS. The synthesized compounds were evaluated for their cell growth inhibition potential using MTT and wound healing assay, 13 compounds induced concentration dependent inhibition with IC50 below 10 μM against breast cancer cell lines (MCF‐7). Further, the molecular docking simulation were carried out for all the derivatives, amongst these thio phenacyl, 2,4‐dichlorophenyl 9H‐indeno [1,2,4]‐Triazolo[1,5‐a]pyrimidin‐9‐one (5 g) shows good binding interaction with amino acid residues. This is further confirmed by wound healing assay which shows that 5 g inhibits cell migration at increasing concentrations. [ABSTRACT FROM AUTHOR]

Abstract In June 2023, the Purine and Pyrimidine Society (PPS) organized the 20th biennial symposium on Purine and Pyrimidine metabolism (PP23). The symposium was organized in Los Angeles, California, USA, by Pr Caius Radu affiliated to UCLA. The scientific program covered various topics such as inborn errors, cancer, immunity, enzymatic reactions, drug development etc and was presented at 9 sessions over three days. The current issue of Nucleosides, Nucleotides & Nucleic Acids is a special issue covering proceedings from PP23-presentations and other PPS-related manuscripts, and in this editorial, we will give an overview of the scientific program of the meeting. [ABSTRACT FROM AUTHOR]

The starting substrate 5-chloro-4,9-dimethoxy-7-oxo-7H-furo[3,2-g]chromene-6-carbonitrile (2) was efficiently synthesized from chlorination of the corresponding hydroxy derivative. The presence of adjacent cyano and chloro functions was employed for construction a variety of five, six and seven membered rings annulated furo[3,2-g]chromenes. Treating precursor 2 with hydrazine, phenylhydrazine and hydroxylamine yielded furo[3,2:6,7]chromeno[4,3-c]pyrazoles 3, 4 and furo[3,2:6,7] chromeno[3,4-d]isoxazole 5, respectively. Also, reaction of compound 2 with a diversity of 1,3-N,N-binucleophiles such as guanidine, cyanoguanidine, thiourea, acetamidine and benzamidine produced annulated furo[3,2:6,7]chromeno[4,3-d]pyrimidines 6–10, respectively. Further, treatment of compound 2 with a variety of 1,4-binucleophiles namely ethylenediamine, o-phenylenediamine and 2-aminophenol yielded furo[3,2:6,7]chromeno[4,3-e][1,4]diazepine 11, furo[3,2:6,7]chromeno[4,3-b][1,5]benzodiazepine 12 and furo[3,2:6,7]chromeno[4,3-b][1,5]benzoxazepine 13, respectively. Some of the synthesized compounds seemed good antimicrobial activity especially compounds 3, 6 and 8. Using analytical and spectral results, the structures of the prepared compounds were established. [ABSTRACT FROM AUTHOR]

Novel five-membered ring (pyrrole, pyrazole and imidazole)-based pyrimidine and quinazoline derivatives were synthesized by one-pot domino approach. This approach has the advantages of high yield, mild reaction conditions and a simple work-up procedure. The structure of the synthesized compound was elucidated by spectroscopy technique and elemental analysis. The synthesized compound were examined for antimicrobial activity against four bacteria (E. coli, S. pyogenes, S. aureus, and P. aeruginosa) and two fungi (C. albicans and A. clavatus) and most of the synthesized compound exhibited moderate to good activity against reference drug ampicillin, ciprofloxacin, norfloxacin, gentamycin, nystatin and griseofulvin, respectively. [ABSTRACT FROM AUTHOR]

Opportunistic infections like tuberculosis (TB) are prevalent in HIV‐infected individuals. In an approach to introducing an industrial‐scale microwave‐assisted production of agents having both antiviral and antibacterial properties, a set of hydrophilic 2,3‐substituted quinazolinones, 4‐oxo‐2‐phenylquinazoline‐3(4H)‐carboximidamide (Qg) and 4‐oxo‐2‐phenylquinazoline‐3(4H)‐carboxamide (Qu), were afforded in encouraging yields. They were obtained by treating 2‐benzamidobenzoyl chloride with guanidine hydrochloride or urea in the presence of potassium carbonate in DMF. DFT calculations were employed for geometrical optimization and vibrational frequency analysis of the compounds. Free energies of solvation (ΔGsol) of Qg, and Qu calculated using DFT lend evidence in support of their hydrophilicity The anti‐HIV‐1 activities of the small‐molecule quinazolinone derivatives Qg and Qu were investigated. The synthons under in vitro conditions inhibit the entry of HIV in receptor cells with low cytotoxicity (EC50=50.53 nM for Qu and EC50=97.92 nM for Qg). The study identifies the antiviral properties of the two benzo‐fused pyrimidine derivatives, which were earlier reported to have antitubercular activity. Our findings indicate the scope for further synthetic explorations of these quinazolinone scaffolds that can lead to developing promising alternatives in drug design, pharmaceutics, and clinical research. [ABSTRACT FROM AUTHOR]

A new set of pyrazolo[1,5-a]pyrimidines 5–8 and imidazo[1,2-b]pyrazoles 9–11 incorporating isoxazole as pharmacologically attractive cores were synthesized starting with aminopyrazole derivative 4. Moreover, the treatment of arylidine derivative 3 with hydroxylamine hydrochloride as nucleophilic reagent afforded the isoxazole derivative 12. All the new target derivatives were assessed in vitro antimicrobial candidates against six strains (three Gram + ve Bacteria and three Gram -ve Bacteria) and two fungi. Target compounds 4, 5, 6, 9 and 10 illustrated potent activity against some of the pathogens compared to the reference drug Ampicillin with minimum inhibitory concentration (MIC) values in some cases less than the reference the other derivatives represented moderate to week and in some cases inactive as a compound 8. Compounds 4, 5, 6 and 10 showed moderate activity against fungi. Finally, antioxidant activities were performed for the most promising targets (except 3a,b and 8) which displayed moderate to very strong antioxidant activities. [ABSTRACT FROM AUTHOR]