Design, Synthesis, and In Silico and In Vitro Cytotoxic Activities of Novel Isoniazid–Hydrazone Analogues Linked to Fluorinated Sulfonate Esters

• Published in: ACS omega 2024-04, Vol.9 (15), p.17551-17562
• Main Authors: Başaran, Eyüp, Tür, Gulal, Akkoc, Senem, Taskin-Tok, Tugba
• Format: Article
• Language: English
• ISSN: 2470-1343; 2470-1343
• DOI: 10.1021/acsomega.4c00652

Cancer is a life-threatening disease, and significant efforts are still being made to treat it. In this study, we synthesized and characterized novel hybrid molecules (10–18) containing hydrazone and sulfonate moieties and tested their cell growth inhibitory effect on human colon cancer cells (DLD-1), human prostate cancer cells (PC3), and human embryonic kidney cells (HEK-293T) using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method for 72 h. In cell culture studies, all tested hybrid molecules except for 12 and 13 showed significant cytotoxic activities at a micromolar level with IC50 values in the range of 10.28–214.0 μM for the PC3 cell line and 13.49–144.30 μM for the DLD-1 cell line. Compounds 4 (10.28 μM) and 5 (11.22 μM) demonstrated the highest cytotoxicity against the PC3 cell line. Against the DLD-1 cell line, compounds 1 (22.53 μM), 4 (13.49 μM), 5 (19.33 μM), 6 (17.82 μM), 8 (24.71 μM), 9 (17.56 μM), and 10 (17.90 μM) in the series showed anticancer activity at lower micromolar levels compared to cisplatin (26.70 μM). Moreover, the study was handled computationally, and molecular docking studies were performed for compounds 1, 4, and 5 for PC3-FAK and PC3-Scr and compounds 4, 6, and 9 for the DLD-1-TNKS target. In this study, compound 4 was found to be the most effective and promising molecule for both targets.