Anti-cancer effect of Indanone-based thiazolyl hydrazone derivative on colon cancer cell lines

Abstract

Colorectal cancer is the third leading cause of cancer related deaths in the United States. Currently, Irinotecan, a topoisomerase I inhibitor, is an approved anti-cancer drug for the treatment of patients with advanced or recurrent colorectal cancer. Considering low response rate and events of high toxicity caused by irinotecan, we evaluated a series of thirteen thiazolyl hydrazone derivatives of 1-indanone for their potential antineoplastic activity and four compounds showed promising anti-cancer activity against most of the tested colon cancer cell lines with IC₅₀ values ranging from 0.41 ± 0.19 to 6.85 ± 1.44 μM. It is noteworthy that the compound, N-Indan-1-ylidene-N'-(4-Biphenyl-4-yl-thiazol-2-yl)-hydrazine (ITH-6) is found to be more effective than irinotecan against colon cancer cells, HT-29, COLO 205, and KM 12. Mechanistic studies reveal that ITH-6 arrests these cancer cell lines in G2/M phase of the cell cycle, induces apoptosis and causes an increase in ROS level with a significant reduction in the GSH level. The mechanism of inhibition relates to the inhibition of tubulin polymerization in the mitotic phase. These findings suggest that ITH-6 is a novel drug candidate for the treatment of colorectal cancer.

Keywords: Anti-cancer; Cell cycle; Indanone; Irinotecan; Thiazolyl hydrazone.