Targeted potent antimicrobial benzochromene-based analogues: synthesis, computational studies, and inhibitory effect against 14α-Demethylase and DNA Gyrase

Abstract 7H-Benzo[7,8]chromeno[2,3-d]pyrimidin-9(8H)-amine (6a,b) have been synthesized via hydrazinolysis of the imidates (5a,b). Polysubstituted chromenotriazolopyrimidine (7a-j), (12a,b) and Schiff base (8a,b) derivatives have also been prepared. The new heterocyclic derivatives were affirmed by spectral data. The target compounds have been screened for antibacterial and antifungal activity. Compounds 6a,b and 7a-c, g-h displayed the most favorable antimicrobial activities in resemblance to the reference antimicrobial agents by IZ range over 24 mm. In addition, MIC, MBC and MFC were also tested and screen for most active compound 6a by 6.25 µg/mL showing bactericidal effect. SAR study revealed that the antimicrobial vitality of the target compounds was safely influenced by the lipophilicity substituents and the calculated log P value. The potent compounds were subjected into in vitro enzyme screening (14α-Demethylase and DNA Gyrase) against both interesting targets and showed good inhibitory profile. Molecular modeling analyses were introduced and discussed focusing on the docking of active compounds into two essential targets, and their ADMET properties were studied.