Akademik Veri Yönetim Sistemi
Istanbul Journal of Pharmacy, cilt.51, sa.2, ss.160-166, 2021 (ESCI, TRDizin)
Background and Aims: Since 1980's, several preclinical studies have been published on the anti-colorectal cancer activity ofthe nonsteroidal anti-inflammatory drug indomethacin. The direct anti-proliferative effect of indomethacin seems to occur viaa variety of reported COX-independent mechanisms. Acemetacin is a glycolic acid ester derivative of indomethacin and contraryto indomethacin, there is not much published research on anti-cancer effects of acemetacin. Herein, we compared the in vitroanti-proliferative properties of indomethacin, acemetacin, and their tromethamine salts in HCT116 colon cancer cells.Methods: The tromethamine salts of indomethacin and acemetacin were synthesized and the structures were established bymicroanalysis, IR, 1H-NMR, 13C-NMR (APT) and 2D-NMR (HSQC and HMBC) spectrometry. Cell proliferation assays were performed using xCELLigence real-time cell analysis system.Results: Indomethacin exhibited profound inhibitory effects with IC50 values at low micromolar ranges. Acemetacin exhibitedfar lower cytotoxic activity as compared to that of indomethacin. Surprisingly, indomethacin-tromethamine salt was 2-fold and4.4-fold more potent than indomethacin at 48 and 72 h, respectively, while maintaining its activity at 24 h. The tromethamine saltof acemetacin was more potent than acemetacin at 24 h and 48 h post-treatment.Conclusion: The anti-proliferative effect of indomethacin in HCT116 cells was found to be at low micro-molar levels. The esterification of indomethacin with glycolic acid caused a strong decrease in anti-proliferative effect. The salt formation caused apositive effect on the anti-proliferative activity of indomethacin and indomethacin-tromethamine salt may be a promising candidate for additional in vivo studies