Title:1,3,4-oxadiazole-2-thione Derivatives; Novel Approach for Anticancer and Tubulin Polymerization Inhibitory Activities
VOLUME: 16 ISSUE: 2
Author(s):Mohamed Abdel-Aziz, Kamel A. Metwally, Amira M. Gamal-Eldeen and Omar M. Aly
Affiliation:Postal address: Medicinal Chemistry Department, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
Keywords:Anticancer, immunofluorescence, 1, 3, 4-oxadiazole, tubulin.
Abstract:A series of novel 5-(substituted phenyl)-3-[(substituted phenylamino)methyl]-3H-[1,3,4]oxadiazole-2-
thione derivatives were prepared and their in vitro cytotoxicity was evaluated against a panel of three cancer cell
lines, namely, hepatocarcinoma HepG2, breast adenocarcinoma MCF-7, and leukemia HL-60 cells, using the
widely accepted MTT assay. In general, the synthesized compounds displayed weak to moderate cytotoxic activity
against the three tested cell lines. Compound 5a, which has trimethoxy substituents on both phenyl rings, exhibited
the highest cytotoxic effect against all cell lines tested with IC50 values of 12.01, 7.52 and 9.7 μM against HepG2,
MCF-7 and HL-60 cells, respectively. Mechanistic studies revealed that the test compounds showed a good
inhibitory effect on cellular tubulin of hepatocellular carcinoma. Compound 5h was the most potent tubulin
inhibitor in HepG2 cells, with 81.1 % inhibition of the original control tubulin. Moreover, the mechanism of tubulin polymerization
inhibition was confirmed by immunofluorescence assay, flow cytometry, and docking study.
