Antiproliferative activity and molecular docking studies of new 4-oxothiazolidin-5-ylidene acetate derivatives containing guanylhydrazone moiety

A new series of 4-oxothiazolidin-5-ylidene acetates ( 1-16 ) containing guanylhydrazone moiety were designed and synthesized by using dimethyl acetylenedicarboxylate (DMAD) as a Michael acceptor. The structure of synthesized compounds was characterized by various spectral techniques including FTIR, H-1 NMR, C-13 NMR and elemental analysis. Synthesized compounds were evaluated for their antiproliferative activity against two human cancer cell lines, A549 (human lung carcinoma cell line) and MDA-MB-231 (human breast adenocarcinoma cell line). Some of these compounds exhibit good antiproliferative activity in both cell lines. For example, compounds 1, 4, 9, 10, 12 and 15 . Particularly, compounds 1, 9 and 10 showed the most potent activity against MDA-MB-231 cells with IC50 10.01, 7.72 and 9.61 mu M respectively which is comparable to that of standard drug cisplatin and ploxal-S. Additionally, compounds that exhibited good activity were further investigated for their cytotoxicity against human healthy cell line (Wl-38). It was deduced from the MTT results that these compounds (1, 4, 9, 10 and 12), which have toxic effects on cancer cells, showed selectivity on healthy cells. Furthermore, molecular docking studies reviewed the interaction between the most active compound 9 to Caspase 9 protein of breast cancer and human lung cancer cells protein. (c) 2022 Elsevier B.V. All rights reserved.