Synthesis, crystal structure and evaluation of anticancer activities of some novel heterocyclic compounds based on thymol

Abstract

A series of novel 1,3,4-thiadiazole, 1,3-thiazole and 1,3-thiazolidin-4-one derivatives bearing thymol were synthesized via cyclization of the corresponding thiosemicarbazones with acetic anhydride, ethyl bromoacetate, dimethyl acetylene dicarboxylate and phenacyl bromides. The structures of the newly synthesized compounds have been confirmed by IR, 1H NMR, 13C NMR, HRMS and single crystal X-ray diffraction analyses. All new thiosemicarbazones and their heterocyclic derivatives were evaluated for their in vitro cytotoxicity against four selected human cancer cell lines, namely, breast adenocarcinoma (MCF-7, MDA-MB- 231), lung carcinoma (A-549) and fibrosarcoma (HT-1080) cell line and compared with reference drug doxorubicine. The data illustrate that most target compounds show moderate to high cytotoxicity activities against the four human cancer cell lines. Especially, thiosemicarbazones 4b showed significant cytotoxicity on HT-1080 and A-549 cancer cell line with an IC50 values of 7.10 ± 0.32 and 14.40 ± 0.36 µM, respectively. Notably, induction of apoptosis by the compound 4b on HT-1080 and A-549 cells was evaluated using different staining techniques such as annexin V-FITC/PI. Moreover, flow-cytometric analysis also revealed that compound 4b caused arrest at the G2/M phase of the cell cycle and caspase-dependent apoptosis in HT-1080 and A-549 cells.