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 ۱۸.۹۳ - ۷۵.۴۸ µM and their best-docked poses identified interaction with PTPase Tyr۳۱۸, His۳۳۶, and His۳۵۲. 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.

کلیدواژه ها:

phenothiazines ، Antimicrobial ، peptidoglycan transpeptidase ، docking ، binding mode