DOCKING AND BIOLOGICAL SCREENING OF BENZO[A]PHENOTHIAZINONES AS NOVEL INHIBITORS OF BACTERIAL PEPTIDOGLYCAN TRANSPEPTIDASE

Document Type: Research Article

Authors

1 Department of Pure and Industrial Chemistry, University of Nigeria, Nsukka, Nigeria

2 Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka

3 University of Nigeria, Nsukka, Enugu, Nigeria

Abstract

Rising cases of antibiotic resistant bacteria is 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. In addition, the identified essential residues could be targeted during the rational optimization of the analogues.

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