Synthesis and molecular docking of some new thiazolidinone and thiadiazole derivatives as anticancer agents

Ali Saeed; Ahbarah M Soliman; Mahmood M S Abdullah; Ehab Abdel-Latif; Amr El-Demerdash

doi:10.1002/cbdv.202301870

Synthesis and molecular docking of some new thiazolidinone and thiadiazole derivatives as anticancer agents

Chem Biodivers. 2024 Mar 27:e202301870. doi: 10.1002/cbdv.202301870. Online ahead of print.

Authors

Ali Saeed¹, Ahbarah M Soliman², Mahmood M S Abdullah³, Ehab Abdel-Latif⁴, Amr El-Demerdash⁵

Affiliations

¹ Mansoura University, Chemistry, AL-Mansoura street, 35516, Mansoura, EGYPT.
² Omar Al-Mukhtar University, Chemistry, Al-Bayda, 919, Al-Bayda, LIBYAN ARAB JAMAHIRIYA.
³ King Saud University, Chemistry, Riyadh, 11451, Riyadh, SAUDI ARABIA.
⁴ Mansoura University, Chemistry, AL-Mansoura street, Mansoura, 35516, Mansoura, EGYPT.
⁵ Norwich University, Chemistry, Norwich, Norwich, UNITED KINGDOM.

PMID: 38538544
DOI: 10.1002/cbdv.202301870

Abstract

New sets of functionalized thiazolidinone and thiadiazole derivatives were synthesized, and their cytotoxicity was evaluated on HepG2, MCF-7, HTC-116, and WI38 cells. The synthetic approach is based on the preparation of 4-(4-acetamidophenyl)thiosemicarbazide (4) and their thiosemicarbazones 5a-e, which are converted to the corresponding thiazoldin-4-one compounds 6a-e upon cyclization with ethyl bromoacetate. The thiadiazole compounds 9 and 12 were obtained by reacting 4-(4-acetamidophenyl)thiosemicarbazide with isothiocyanates and/or ethyl 2-cyano-3,3-bis(methylthio)acrylate, respectively. The thiazolidinone compounds 6c and 6e exhibited strong cytotoxicity against breast cancer cells, with an IC50 (6.70±0.5 µM) and IC50 (7.51±0.8 µM), respectively, very close to that of doxorubicin (IC50: 4.17±0.2 µM). In addition, the anti-cancer properties of the tested thiazolidinone and thiadiazole scaffolds were further explored by the molecular docking program (MOE)-(PDB Code-1DLS). Compounds 5d, 5e, 6d, 6e, and 7 have the best binding affinity, ranging from -8.5386 kcal.mol-1 to -8.2830 kcal.mol-1.

Keywords: 4-Aminoacetanilide; HepG2; Thiadiazole; docking; thiazolidin-4-one.