Novel N-Acyl Hydrazone Compounds as Promising Anticancer Agents: Synthesis and Molecular Docking Studies.

In this study, a new series of N-acyl hydrazones 7a-e, 8a-e, and 9a-e, starting from methyl δ-oxo pentanoate with different substituted groups 1a-e, were synthesized as anticancer agents. The structures of obtained target molecules were identified by spectrometric analysis methods (FT-IR, 11H NMR, 13C NMR, and LC-MS). The antiproliferative activity of the novel N-acyl hydrazones was evaluated on the breast (MCF-7) and prostate (PC-3) cancer cell lines by an MTT assay. Additionally, breast epithelial cells (ME-16C) were used as reference normal cells. All newly synthesized compounds 7a-e, 8a-e, and 9a-e exhibited selective antiproliferative activity with high toxicity to both cancer cells simultaneously without any toxicity to normal cells. Among these novel N-acyl hydrazones, 7a-e showed the most potent anticancer activities with IC50 values at 7.52 ± 0.32-25.41 ± 0.82 and 10.19 ± 0.52-57.33 ± 0.92 µM against MCF-7 and PC-3 cells, respectively. Also, molecular docking studies were applied to comprehend potential molecular interactions between compounds and target proteins. It was seen that the docking calculations and the experimental data are in good agreement.

Cytotoxic Activity and Docking Studies of 2-arenoxybenzaldehyde N-acyl Hydrazone and 1,3,4-Oxadiazole Derivatives against Various Cancer Cell Lines.

To understand whether previously synthesized novel hydrazone and oxadiazole derivatives have promising anticancer effects, docking studies and in vitro toxicity assays were performed on A-549, MDA-MB-231, and PC-3 cell lines. The antiproliferative properties of the compounds were investigated using molecular docking experiments. Each compound's best-docked poses, binding affinity, and receptor-ligand interaction were evaluated. Compounds' molecular weights, logPs, TPSAs, abilities to pass the blood-brain barrier, GI absorption qualities, and CYPP450 inhibition have been given. When the activities of these molecules were examined in vitro, for the A-549 cell line, hydrazone 1e had the minimum IC50 value of 13.39 µM. For the MDA-MB-231 cell line, oxadiazole 2l demonstrated the lowest IC50 value, with 22.73 µM. For PC-3, hydrazone 1d showed the lowest C50 value of 9.38 µM. The three most promising compounds were determined as compounds 1e, 1d, and 2a based on their minimum IC50 values, and an additional scratch assay was performed for A-549 and MDA-MB-231 cells, which have high migration capacity, for the three most potent molecules; it was determined that these molecules did not show a significant antimetastatic effect.