docking and biological screening of bezo[a]phenothiazinones as novel inhibitors of bacterial peptidogloycan transpeptidase

Rising cases of antibiotic-resistant bacteria is a public health concern. many approved antibiotics target penicillin-binding proteins example peptidoglycan transpeptidase (ptpase). due to wide pharmacological activity of phenothiazines, new styryl, aryl, alkynyl, and thiophenyl benzo[a]phenothiazines were synthesized and their inhibitory potency against ptpasein silico and gram-positive/gram-negative bacteria evaluated. the compounds inhibited the activity of ptpase at 18.93 - 75.48 μm and their best-docked poses identified interaction with ptpase tyr318, his336, and his352. experimental results agreed with computational predictions and further confirmed the benzo[a]phenothiazines as potential antibiotics. also, the identified essential residues could be targeted during the rational optimization of the analogs.