Docking and Biological Screening of Bezo[A]phenothiazinones as Novel Inhibitors of Bacterial Peptidogloycan Transpeptidase

Document Type: Research Article


1 Department of Pharmaceutical and Medicinal Chemistry, University of Nigeria, Nsukka, NIGERIA

2 Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, California, USA.

3 Department of Pure and Industrial Chemistry, University of University, Nsukka, NIGERIA


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.


Main Subjects

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