New thiazolopyrimidine and dithiazolopyrimidinone derivatives 2-11 were synthesized and estimated for antimicrobial activity against S. aureus, B. cereus, E. coli, C. albicans, A. fumigatus and A. terreus. The attained results proved that 4, 8a and 11g have significant effectiveness against S. aureus and B. cereus. On the other hand, 7, 10b, 10c and 11h exhibited prominent activity against B. cereus, whereas 8a, 10b and 11g were proved to be active against E. coli. From another point of view, 4 and 8a exhibited promising efficacy against A. fumigatus and A. terreus; moreover, 8a showed outstanding efficacy against C. albicans. Quorum-sensing inhibitory activity of the new compounds was esteemed against C. violaceum, where 7, 8a, 9b, 10a-c, 11d and 11g have acceptable efficacy. In vitro antitumor efficacy of the same compounds against HepG2, HCT-116 and MCF-7 cancer cell lines was also tested. Compounds 4 and 11h showed enhanced effectiveness against the three cell lines, whereas 10b displayed eminent activity against HCT-116 and MCF-7 cells. Moreover, 11a was found to have outstanding activity against MCF-7 cells, while 11i showed promising efficacy against HepG2 cells. The in vitro active antitumor compounds were evaluated for in vivo antitumor effectiveness against EAC in mice, as well as in vitro cytotoxicity against WI38 and WISH normal cells. Results manifested that 4 has the strongest in vivo activity, and that all investigated analogs are less cytotoxic than 5-FU against both normal cell lines. DNA-binding affinity of the active compounds was examined, where 4, 8a, 10c, 11d and 11g,h displayed strong affinity. In silico studies proved that majority of the analyzed compounds are in conformity with the optimum needs for good oral absorption.
Keywords: Antimicrobial; Antiquorum-sensing; Antitumor; DNA-binding; Dithiazolopyrimidinones; In silico studies; Thiazolopyrimidines.
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