In this article, three series of dihydrotriazine derivatives bearing a quinoline moiety (5a, 5b, 8a-8c, and 9a-9m) have been designed, synthesized, and evaluated as antibacterial agents. Compounds 8a-8c were found to be the most potent of all of the compounds tested with an MIC value of 1 μg/mL against several Gram-positive (S. aureus 4220 and MRSA CCARM 3506) and Gram-negative (E. coli 1924) strains of bacteria. In addition, 3-[4-amino-6-(phenethylamino)-2,5-dihydro-1,3,5-triazin-2-yl)-6-[(3-chlorobenzyl)oxy]quinolin-2-ol (8a) showed potent inhibitory activity (MIC=2 μg/mL) against Pseudomonas aeruginosa 2742, indicating that its antibacterial spectrum is similar to those of the positive controls gatifloxacin and moxifloxacin. Structure-activity relationships (SAR) analyses and docking studies implicated the dihydrotriazine group in increasing the antimicrobial potency of the quinoline compounds. In vitro enzyme study implied that compound 8a also displayed DHFR inhibition.
Keywords: DHFR inhibition; antibacterial agents; antifungal activity; biological activity; dihydrotriazine; quinoline; synthesis design.
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