In silico study of the interaction of phenazines with tuberculostatic activity with known molecular targets of Mycobacterium tuberculosis

Abstract

Phenazines derived from β-lapachone had tuberculostatic activity reported in the literature. However, very little is known about their mechanism of action or molecular targets. In order to investigate this, we performed an in silico study through molecular docking and molecular dynamics simulations, meant to evaluate the interactions of ten phenazines (active or not) with the molecular targets for rifampicin, isoniazid and ethambutol, three drugs used in the treatment of tuberculosis. The results showed that these phenazines might bind to the enzyme arabinosyltransferase from Mycobacterium tuberculosis, the same molecular target of ethambutol. The results obtained in this work open the perspective to design and synthesis of new phenazinic inhibitors of arabinosyltransferase from M. tuberculosis.

Keywords

• Phenazines
• Ethambutol
• Tuberculosis
• Arabinosyltransferase
• Molecular docking
• Molecular dynamics