Uracil-coumarin based hybrid molecules as potent anti-cancer and anti-bacterial agents

Publication date: Available online 12 December 2019Source: Journal of Saudi Chemical SocietyAuthor(s): Mohit Sanduja, Jyoti Gupta, Harbinder Singh, Piyusha P. Pagare, Abhineet RanaAbstractIn the current report, we have rationally designed a series of uracil-coumarin based bifunctional molecular hybrids roped by 1,2,3-triazole moiety. The designed compounds were synthesized and tested against a panel of six human cancer cell lines namely Colo-205, MCF-7, A-549, PA-1, PC-3 and Hela cells by Sulforhodamine B assay. The results indicated that the hybrid molecules can specifically inhibit the MCF-7 cancer cell proliferation amongst which A-2 was found to be most potent hybrid (GI50 = 1.55 µM) with fluorine atom as R with two carbon chain length between triazole and coumarin moieties. Cell cycle analysis revealed that A-2 significantly arrest the G2/M phase to inhibit proliferation of MCF-7 cells. Due to its mitotic arrest, A-2 was further analyzed to predict its various binding interactions within the active site of tubulin, which revealed its best binding pattern within the colchicine binding site. In addition to this, antibacterial potential of all the synthetics was also evaluated which resulted in two hit lead molecules A-2 (MIC= 11.7 μg/ml) and A-3 (MIC= 7.23 μg/ml) that can significantly inhibit the bacterial strain Staphylococcus aureus comparable to that of standard drug levofloxacin (MIC= 3.12 μg/ml). Binding interactions within the active site of dihydrofolate reduct...
Source: Journal of Saudi Chemical Society - Category: Chemistry Source Type: research