Development of 1,3,4-oxadiazole thione based novel anticancer agents: Design, synthesis and in-vitro studies

- Fifteen new mannich bases of 1,3,4-oxadiazole thiones have been designed and synthesized in order to screen for their anticancer activity on 4 cancerous cell lines viz HeLa, U-87, Panc and MCF-7.
- 3i and 3j showed best apoptotic activity on HeLa cervical cancer cells.
- 3i and 3j caused induction of phosphatidyl serine externalization, fragmentation of DNA, increase in the bax/bcl2 ratio, cleavage of PARP and procaspase-3 proteins.
- 3i and 3j arrested cells in G2-M phase of the cell cycle in flow cytometry analysis.
- 3i and 3j significantly increased expression of p21 and downregulated the expression of cyclin B1.

A series of new 1,3,4-oxadiazole-2(3H)-thione analogues (3a to 3o) have been designed, synthesized and evaluated for their anticancer activity. Four different cancerous cell lines viz. HeLa (cervical), U-87 (glioblastoma), Panc (pancreatic) and MCF-7 (breast) were used to assess the potency of the synthesized compounds as anticancer agents. Among them 3i and 3j showed promising cytotoxicity against HeLa cell line. Further, 3i and 3j successfully inhibited cell cycle progression and displayed cell death in HeLa cells via apoptosis as visualized by Annexin V APC and DNA fragmentation assay. 3i and 3j induced caspase-3 activation, PARP cleavage, increase in expression of proapoptotic protein Bax and decrease in the expression of antiapoptotic protein Bcl-2. Also, 3i and 3j induced overexpression of p21 and decreased expression of cyclin B1 indicating the arrest of cells in G2-M phase of the cell cycle. Therefore, new lead compounds are being suggested having anticancer activity through cell cycle inhibition and apoptosis.

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