Bile-Acid-Appended Triazolyl Aryl Ketones: Design, Synthesis, In Vitro Anticancer Activity and Pharmacokinetics in Rats.

A library of bile-acid-appended triazolyl aryl ketones was synthesized and characterized by detailed spectroscopic techniques such as H and C NMR, HRMS and HPLC. All the synthesized conjugates were evaluated for their cytotoxicity at 10 µM against MCF-7 (human breast adenocarcinoma) and 4T1 (mouse mammary carcinoma) cells. In vitro cytotoxicity studies on the synthesized conjugates against MCF-7 and 4T1 cells indicated one of the conjugate to be most active against both cancer cell lines, with IC values of 5.71 µM and 8.71 µM, respectively, as compared to the reference drug docetaxel, possessing IC values of 9.46 µM and 13.85 µM, respectively. Interestingly, another compound (IC = 2.61 µM) was found to possess pronounced anticancer activity as compared to the reference drug docetaxel (IC = 9.46 µM) against MCF-7. In addition, the potent compounds ( and ) were found to be non-toxic to normal human embryonic kidney cell line (HEK 293), as evident from their cell viability of greater than 86%. Compound induces higher apoptosis in comparison to (46.09% vs. 33.89%) in MCF-7 cells, while similar apoptotic potential was observed for and in 4T1 cells. The pharmacokinetics of in Wistar rats showed an MRT of 8.47 h with a half-life of 5.63 h. Clearly, these results suggest to be a potential candidate for the development of anticancer agents.