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

Eyüp Başaran; Gulal Tür; Senem Akkoc; Tugba Taskin-Tok

doi:10.1021/acsomega.4c00652

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

ACS Omega. 2024 Apr 5;9(15):17551-17562. doi: 10.1021/acsomega.4c00652. eCollection 2024 Apr 16.

Authors

Eyüp Başaran¹, Gulal Tür², Senem Akkoc^{3

4}, Tugba Taskin-Tok^{5

6}

Affiliations

¹ Department of Chemistry and Chemical Processing Technologies, Vocational School of Technical Sciences, Batman University, Batman 72060, Turkey.
² Department of Chemistry, Graduate Education Institute, Batman University, Batman 72100, Turkey.
³ Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Suleyman Demirel University, Isparta 32260, Turkey.
⁴ Faculty of Engineering and Natural Sciences, Bahçeşehir University, Istanbul 34353, Turkey.
⁵ Department of Chemistry, Faculty of Arts and Sciences, Gaziantep University, Gaziantep 27310, Turkey.
⁶ Department of Bioinformatics and Computational Biology, Institute of Health Sciences, Gaziantep University, Gaziantep 27310, Turkey.

Abstract

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.