Synthesis, Biological Evaluation, and Molecular Modeling Studies of New 1,3,4-Thiadiazole Derivatives as Potent Antimicrobial Agents.

In this work, the synthesis, characterization, and biological activities of a new series of 1,3,4-thiadiazole derivatives were investigated. The structures of final compounds were identified using 1 H-NMR, 13 C-NMR, elemental analysis, and HRMS. All the new synthesized compounds were then screened for their antimicrobial activity against four types of pathogenic bacteria and one fungal strain, by application of the MIC assays, using Ampicilin, Gentamycin, Vancomycin, and Fluconazole as standards. Among the compounds, the MIC values of 4 and 8 µg/mL of the compounds 3f and 3g, respectively, are remarkable and indicate that these compounds are good candidates for antifungal activity. The docking experiments were used to identify the binding forms of produced ligands with sterol 14-demethylase to acquire insight into relevant proteins. The MD performed about 100 ns simulations to validate selected compounds' theoretical studies. Finally, using density functional theory (DFT) to predict reactivity, the chemical characteristics and quantum factors of synthesized compounds were computed. These results were then correlated with the experimental data. Furthermore, computational estimation was performed to predict the ADME properties of the most active compound 3f.

Design, synthesis, molecular docking and molecular dynamics studies of novel triazolothiadiazine derivatives containing furan or thiophene rings as anticancer agents.

Breast cancer is the most common cancer type amoung post-menopausal women. Aromatase inhibitors were used in the treatment of patients. However, drug resistance may develop in long-term drug use, especially in 3rd and 4th stage (advanced) cancer cases. Therefore, there is a constant need for new agents. In this study, new triazolothiadiazine derivatives were synthesized and their anticancer activities were investigated. Compounds 2k, 2s, and 2w showed inhibitor activity against MCF-7 cell line with IC50 = 4.63 ± 0.10; 2.23 ± 0.16; 3.13 ± 0.08 µM value, respectively. As a result of in vitro aromatase enzyme inhibition test, compound 2s was the most active derivative with IC50 = 0.058 ± 0.023 µM. In addition, DNA synthesis inhibition percentages of the compounds were measured by the BrdU method. The intermolecular interactions of the promising compounds with aromatase enzyme were investigated through the SP docking approach, which revealed significant binding interaction energies associated with these compounds. Following that, the interaction's stability was assessed using a typical atomistic 100 ns dynamic simulation study. A number of parameters derived from MD simulation trajectories were computed and validated for the protein-ligand complex's stability under the dynamic conditions.

Synthesis and the selective antifungal activity of 5,6,7,8-tetrahydroimidazo[1,2-a]pyridine derivatives.

Even though there are new classes of compounds now frequently used in treatment of fungal infections, the density of deeply invasive candidiasis has increased at least 10-fold during the past decade. Furthermore, many infections due to Candida species are actually refractory to antifungal therapy. In this present study, it was aimed to synthesize, new hydrazide derivatives of tetrahydroimidazo[1,2-a]pyridine and evaluate their anticandidal activity and cytotoxicity in vitro. The reaction of tetrahydroimidazo[1,2-a]pyridine-2-carboxylic acid hydrazides with various benzaldehydes gave tetrahydroimidazo[1,2-a]pyridine-2-carboxylic acid benzylidene hydrazide derivatives. The chemical structures of the compounds were elucidated and confirmed by IR, 1H NMR, MS-FAB+ spectroscopy and elemental analyses. Eight new tetrahydroimidazo[1,2-a]pyridine derivatives were synthesized and screened for their antifungal effects against a panel of ten human pathogenic Candida albicans, Candida glabrata, Candida krusei, Candida parapsilosis, Candida tropicalis, Candida utilis, and Candida zeylanoides using agar diffusion and broth microdilution assays, respectively. Furthermore, their cytotoxicity was tested against six mammalian cell lines. Among the analogues, the compound 5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxylic acid-(4-cyanobenzylidene) showed very strong inhibitory activity (up to MIC 0.016 mg/mL) against the screened Candida species. The same compound showed no in vitro toxicity up to 25 microg/mL concentration suggesting that its antifungal activity (MICs 0.016-1 mg/mL) is selective.