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Based on unselectively, several side effects and drug resistance of available anticancer agents, the development and research for novel anticancer agents is necessary. In this study, a new series of quinazoline-4(3H)-one derivatives having a thiol group at position 2 of the quinazoline ring (8a-8 h) were designed and synthesized as potential anticancer agents. The Chemical structures of all compounds were characterized by 1H-NMR, 13C-NMR, and Mass spectroscopy. The antiproliferative activity of all derivatives were determined against two cancer cell lines (MCF-7 and SW480) and one normal cell lines (MRC-5) by the MTT method. Cisplatin, Erlotinib and Doxorubicin were used as positive controls. The results of in vitro screening showed that 8a with an aliphatic linker to SH group was the most potent compound with IC50 values of 15.85 ± 3.32 and 17.85 ± 0.92 µM against MCF-7 and SW480 cell lines, respectively. 8a indicated significantly better potency compared to Erlotinib in the MCF-7 cell line. The cytotoxic results obtained from testing compound 8a on the normal cell line, revealing an IC50 value of 84.20 ± 1.72 µM, provide compelling evidence of its selectivity in distinguishing between tumorigenic and non-tumorigenic cell lines. Structure–activity relationship indicated that the variation in the anticancer activities of quinazoline-4(3H)-one derivatives was affected by different substitutions on the SH position. Molecular docking and MD simulation were carried out for consideration of the binding affinity of compounds against EGFR and EGFR-mutated. The binding energy of compounds 8a and 8c were calculated at -6.7 and − 5.3 kcal.mol− 1, respectively. Compounds 8a and 8c were found to establish hydrogen bonds and some other important interactions with key residue. The DFT analysis was also performed at the B3LYP/6–31 + G(d, p) level for compounds 8a, 8c and Erlotinib. Compound 8a was thermodynamically more stable than 8c. Also, the calculated theoretical and experimental data for the IR spectrum were in agreement. The obtained results delineated that the 8a can be considered an appropriate pharmacophore to develop as an anti-proliferative agent. [ABSTRACT FROM AUTHOR]

Infectious diseases are still one of the leading causes of death and disability in human society. Synthetic antimicrobial agents have recently emerged as promising candidates against drug‐resistant pathogens. Here we described an efficient procedure for synthesis of aryloxyalkyl theophylline analouges as novel antimicrobial agents. Fourtheen new compounds were synthesized (5 a–5 n) and their chemical structures were approved by different spectroscopic methods. The synthesized compounds were screened for their antimicrobial activities by broth micro dilution method as recommended by Clinical and Laboratory Standards Institute (CLSI). Molecular docking studies were also performed to forecast their binding modes against cytochrome P450 lanosterol 14α‐demethylase as a main target. The results represented appropriate correlation between molecular docking and antimicrobial activity of the compounds. Based on biological results and in silico ADMET (absorption, distribution, metabolism, excretion, and toxicity) predictions, compound 5 g can be considered as an ideal antimicrobial agent for the future studies. [ABSTRACT FROM AUTHOR]

Thirteen novel isatin‐ampyrone Schiff bases derivatives were synthesized in only two steps of 70%–90% overall yields. In vitro cytotoxic activity of these new Schiff bases against three human tumor cell lines (MCF‐7, A549, and SCOV3) as well as normal breast cell line (MCF‐10A) were evaluated by MTT assay. Structure–activity relationship of the tested compounds revealed that chlorine group at C‐5 position of the isatin ring significantly increased the cytotoxic activity. This study generally led to introduce a highly active molecule (M12) with IC50 values of 5.12, 25.5, and 12.9 μΜ, on MCF‐7, A549, and SCOV3, respectively. Furthermore, molecular docking studies of the synthesized compounds were also done to investigate their binding modes towards VEGFR‐2 and JNK3‐MAP kinase as the main targets for isatin‐containing anticancer agents. Binding free energy values of the compounds showed positive correlation with their cytotoxic activities. To confirm the docking results, molecular docking simulations of potent compound (M12) against VEGFR‐2 and JNK3 MAP kinase were also performed. According to the cytotoxic results and in silico ADMET predictions together, M12 can be considered as a potent candidate for the future anticancer studies. [ABSTRACT FROM AUTHOR]

A series of 2-aryl/alkyl-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazines (S1–S11) were synthesized with an eco-friendly and recoverable nanocatalyst (GO-Fe3O4–Ti(IV)) as an efficient magnetic composite. The new nanocatalyst was characterized by FT-IR, XRD and, EDS analysis. A conformable procedure, easy to work up and having a short reaction time with high yields are some advantages of this method. The new catalyst is also thermal-stable, reusable and, environment-friendly. The chemical structures of the synthesized 1,3-oxazine compounds were confirmed by comparing their melting points with those reported in literature. Then, the anticonvulsant activity of these compounds was assessed by the intraperitoneal pentylenetetrazole test (ipPTZ). Compounds S10 and S11 displayed considerable activity against chemically-induced seizure tests. The molecular simulation was also done to achieve their binding affinities as γ‐aminobutyric acid A (GABA‐A) receptor agonists as an assumptive mechanism of their anticonvulsant action. The result of molecular studies represented strongly matched with biological activity. Molecular docking simulation of the potent compound (S10) and diazepam as the positive control was performed and some critical residues like Thr262, Asn265, Met286, Phe289, and Val290 were identified. Based on the anticonvulsant results and also in silico ADME predictions, S11 can be to become a potential drug candidate as an anticonvulsant agent. [ABSTRACT FROM AUTHOR]

Today, fungal infection has become more common disease especially in some cases, such as AIDS, cancer, and organ transplant which the immune system is suppressed. On the other hand, due to the increasing resistance to current antifungal drugs, more and more options for design of novel more efficient compounds with higher resistance are needed. In this study, a series of a fluconazole analogues were subjected to quantitative structure-activity relationship analysis to find the structure requirements for modeling adequate candidate. The best multiple linear regression equation was achieved from GA-PLS and MLR modeling. Subsequently, in silico screening study was applied to found new potent lead compounds based on the resulted model. The ability of the best designed compounds for antifungal activity was investigated by using molecular dynamic (MD) and molecular docking simulation. The results showed that compound F13 can efficiently bind to lanestrol 14-α demethylase target similar to other antifungal azoles. The molecular docking studies revealed an interesting binding profile with very high receptor affinity to the CYP51 active site. The triazole moiety of ligand F13 pointed to HEM group in lanestrol 14-α demethylase site and coordinated to Fe of HEM through its N4 atom. Also, there was a convenient relevance between QSAR and docking results. With the compound F13 which demonstrated the most promising minimum inhibitory concentration (MIC) values, it can be concluded that F13 is appropriate candidate for the development as antifungal agent. [ABSTRACT FROM AUTHOR]

Aromatase inhibitors (AIs) as effective candidates have been used in the treatment of hormone-dependent breast cancer. In this study, we have proposed 300 structures as potential AIs and filtered them by Lipinski's rule of five using DrugLito software. Subsequently, they were subjected to docking simulation studies to select the top 20 compounds based on their Gibbs free energy changes and also to perform more studies on the protein-ligand interaction fingerprint by AuposSOM software. In this stage, anastrozole and letrozole were used as positive control to compare their interaction fingerprint patterns with our proposed structures. Finally, based on the binding energy values, one active structure (ligand 15) was selected for molecular dynamic simulation in order to get information for the binding mode of these ligands within the enzyme cavity. The triazole of ligand 15 pointed to HEM group in aromatase active site and coordinated to Fe of HEM through its N4 atom. In addition, two p-cation interactions was also observed, one interaction between triazole and porphyrin of HEM group, and the other was 4-chloro phenyl moiety of this ligand with Arg115 residue. [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]

• Design and synthesis of a novel series of 1,2,4-triazole derivatives. • The antifungal activity of these compounds were investigated against several yeasts (candida species), filamentous and clinical strains using the CLSI method. • Compounds 7g and 7h were found to be more potent against yeast strains and clinical strain of fluconazole-resistant and fluconazole-sensitive with MIC values of 0.5 µg/mL compared to the Fluconazole as control drug. • Molecular docking study was performed to elucidate the binding mode of these ligands in the active site of 14α-demethylase enzyme as plausible target of azole compounds. Fungal infections are still threatening human health due to resistance to existing drugs, therefore, the design and development of novel antifungal agents is to be necessary and also, is interesting topic for medicinal chemist. Azole derivatives are one of the promising antifungal agents, which exert their activities through inhibition of cytochrome P450 14α-demethylase (CYP51). In this regard, a new series of 1,2,4-triazole derivatives (7a-i) were designed, synthesized and confirmed with IR, 1HNMR, 13CNMR and Mass spectrum. The antifungal activity of these compounds were investigated against several yeasts (candida species), filamentous and clinical strains using the CLSI method. Furthermore, to measure the cytotoxic activity, MTT assay was also done against MRC-5 as normal human fibroblasts cell line. Our results represented that most of the compounds had appropriate activity ranging from 0.5-256 µg/mL, especially, compounds 7g and 7h were found to be more potent against yeast strains and clinical strain of Fluconazole-resistant and Fluconazole-sensitive with MIC values of 0.5 µg/mL compared to the Fluconazole as control drug. Subsequently, molecular docking studies were performed to find the binding energy and interaction mode of these compounds in the active site of 14α-demethylase enzyme as plausible target of azole compounds. According to in vitro antifungal assay and in silico ADME predictions, compounds 7g and 7h can be considered as potent candidates for further studies. [Display omitted] [ABSTRACT FROM AUTHOR]