Abstract
Levonorgestrel, one of the best-known oral contraceptives, has excellent contraception benefits, as well as a variety of non-contraceptive advantages, e.g., for the treatment of menstrual bleeding, dysmenorrhea, premenstrual syndrome, menstrual migraines, acne, and hirsutism. Reduced risk of endometrial, ovarian, and colorectal cancer results from long-term treatment. So, a series of novel 1,2,3-triazole Levonorgestrel derivatives 8-13 were synthesized in 80-92% yield via copper-catalyzed [3+2]-cycloaddition reactions (CuAAC) between the terminal alkyne Levonorgestrel 1 and aromatic azides 2-7. The structures of all the synthesized hybrids were confirmed by H-1 and C-13 NMR and mass spectra and elemental analyses. The in vitro anticancer screening against four human cancer cell lines, including colorectal carcinoma (HCT116), hepatoblastoma (HePG2), prostate cancer (PC3), and breast adenocarcinoma (MCF-7), revealed very strong anticancer activities of compounds 9 and 13, whereas the other compounds (8, 10-12) showed moderate to weak anticancer activities in comparison to the standard drug doxorubicin. To validate the anticancer results, molecular docking experiments were performed. The results of the docking experiments matched well with the results of the in vitro tests.