Design and evaluation of biological activities of 1,3-oxazolidinone derivatives bearing amide, sulfonamide, and thiourea moieties.

1,3-Oxazolidine-2-one is an important heterocyclic ring participating in the chemical structure of many drugs. In this research, 22 new amide/sulfonamide/thiourea derivatives (1-22) were obtained by the reaction of (S)-4-(4-aminobenzyl)-2(1H)-1,3-oxazolidinone with 4-substituted benzoyl chlorides, 4-substituted benzene sulfonyl chlorides, and 4-substituted phenyl isothiocyanates. The structures of all synthesized compounds were clarified by FT-IR, NMR, and mass spectroscopic and elemental analysis techniques. The synthesized compounds were screened for their antimicrobial activity. Antimicrobial susceptibility and cellular physiology were evaluated using the microbroth dilution assay and the flow cytometry method. As a result, it was determined that compound 16 displayed better antimicrobial activity than chloramphenicol against Gram-positive bacteria, especially Staphylococcus aureus. In order to understand the mechanism of effect of the compounds on the cell membrane, fluorescence microscopy was used. Cell membrane damage of the Gram positive bacteria treated with compound 16 was observed as a result of intense staining with propidium iodide. In addition, genotoxicity, cytotoxicity, and absorption, distribution, metabolism, and excretion (ADME) parameters of compound 16 were examined and it was found as non-mutagenic and non-cytotoxic at the concentration at which it showed antimicrobial activity. According to the calculated ADME parameters and drug likeness scores, the compounds can be good drug candidates, especially compound 16.

New piperidine-hydrazone derivatives: Synthesis, biological evaluations and molecular docking studies as AChE and BChE inhibitors.

Hydrazones and the piperidine ring containing compounds were considered as beneficial substrates in drug design. Therefore, this study was aimed at the synthesis of new benzoyl hydrazones derived from ethyl 4-oxopiperidine-1-carboxylate and 2,6-diphenylpiperidin-4-one. The synthesized compounds (1-19) were screened for their antioxidant, anticholinesterase and anticancer activities. The antioxidant capacity of the compounds was evaluated by using four complementary tests. The results showed that compound 7 and 17 have the higher lipid peroxidation inhibitory activity than the other compounds. In DPPH˙ scavenging assay, compounds 5, 6, 10, 14, 17 demonstrated better activity than that of standard BHT, while in ABTS+˙ scavenging assay compound 6 and 17 exhibited better activity among the other compounds. The CUPRAC assay disclosed that compound 2 displayed better activity than α-tocopherol. The anticholinesterase activity was performed against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. Compound 11 (IC50: 35.30 ± 1.11 µM) inhibited BChE better than galantamine (IC50: 46.03 ± 0.14 µM). We conclude that the compound 11 can be considered as a candidate for BChE inhibitor. Moreover docking method was applied to elucidate the AChE and BChE inhibitory mechanism of the compound 11. Molecular docking analysis revealed that compound 11 bound to BChE enzyme more efficiently when compared to the AChE due to its orientations and different types of interactions. In addition, the non-cytotoxic properties of the compounds brought them into prominence, although they did not show significant anticancer properties.