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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]

A series of some novel 4H-benzoxazin-3-one derivative (1a-20a) was designed, synthesized and evaluated as antifungal and anticancer agents. Benzoxazine compounds were synthesized in only two steps. In the first step, o-aminophenols derivatives reacted with chloroacetyl chloride in the presence of K2CO3 to produce a 4H-benzoxazin-3-one intermediate. In the second step, this intermediate was reacted to various alkyl or aryl halides to get the final products. Then, the synthetic benzoxazine compounds were evaluated for their antifungal activity against different species of fungi. Compound 13a MICs GM of 28.5 µg/mL and then compounds 14a, 17a with MICs GM of 47.2 and 50.7 µg/mL demonstrated the most excellent inhibitory activities against Candida strains, respectively. In addition, the potential cytotoxic activities of all compounds were evaluated by two methods: MTT test, and also lactate dehydrogenase test (LDH). According to the biological results, the most of our compounds especially those containing benzyl groups on the nitrogen atom showed significant antifungal activity. Cytotoxic activities of the compounds were also determined on Hep-G2 and SW cell lines by MTT method and LDH. In MTT assay, compounds 5a, 6a and 8a showed the best results (IC50: 3.12 µg/mL) followed by compounds 7a, 13a and 17a (IC50: 6.25 µg/mL) on the Hep-G2 cells. The best cytotoxic compounds against SW cells were 17a and 18a. The LDH assay showed the same results with MTT of SW. [ABSTRACT FROM AUTHOR]

In this study two series of fluconazole derivatives bearing nitrotriazole (series A) or piperazine ethanol (series B) side chain were designed and synthesized and then docked in the active site of lanosterol 14α-demethylase enzyme (1EA1) using the Autodock 4.2 program (The scripps research institute, La Jolla, CA, USA). The structures of synthesized compound were confirmed by various methods including elemental and spectral (NMR, CHN, and Mass) analyses. Then antifungal activities of the synthesized compound were tested against several natural and clinical strains of fungi using a broth microdilution assay against several standard and clinical fungi. Nitrotriazole derivatives showed excellent and desirable antifungal activity against most of the tested fungi. Among the synthesized compounds, 5a-d and 5g, possessing nitrotriazole moiety, showed maximum antifungal activity, in particular against several fluconazole-resistant fungi. [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]

In this study, two series of novel 1,4-benzothiazine-3-one derivatives with alkyl substitution (series 1: 4a-4f) and aryl substitution (series 2: 4g-4l) were designed and synthesized based on the chemical scaffolds of perampanel, hydantoins, progabide and etifoxine as anti-convulsant agents. The chemical structures of the synthesized compounds were confirmed by FT-IR, 1H NMR and 13C NMR spectroscopy. Anti-convulsant effect of the compounds was examined through intraperitoneal pentylenetetrazol (i.p. PTZ) induced epilepsy mouse models. Compound 4h (4-(4-bromo-benzyl)− 4 H-benzo[ b ] [1,4] thiazin-3(4 H)-one) demonstrated a promising activity toward chemically-induced seizure experiment. Molecular dynamics simulation on GABA-Aergic receptors as a plausible mechanism were also done to achieve the binding and orientation of compounds in the active site of the target to evaluate the results of docking and experimental studies. The computational results were confirmed the biological activity. DFT study of 4c and 4h was performed on B3LYP/6–311 G** level of theory. Reactivity descriptors such as HOMO, LUMO, electron affinity, ionization potential, chemical potential, hardness and softness were studied in detail and show that 4h has higher activity than 4c. Also, the frequency calculations were performed on the same level of theory and the results are in line with experimental data. Moreover, in silico ADMET properties were done to establish a relationship between the physiochemical data of the designed compounds and their in-vivo activity. Appropriate plasma protein binding and high blood-brain barrier penetration are the main features of desired in -vivo performance. [Display omitted] • 1,4 benzothiazine 3-one derivatives were synthesized as anticonvulsant agents. • The benzothiazine containing 4-bromo-benzyl substitution, increased the latency of convulsions. • The computational studies and biology assay indicated that compound 4h might had a good inhibitory effect on GABA-A receptor. • The results of the computational study and experimental methods about compound 4h were agreement together. [ABSTRACT FROM AUTHOR]