Molecular docking and in silico studies on analogues of 2-methylheptyl isonicotinate with DHDPS enzyme of Mycobacterium tuberculosis

Abstract

Mycobacterium tuberculosis and other strains of mycobacteria cause tuberculosis which has infected one-third of the world’s population. Moreover, there has been increase in multidrug-resistant strains which spotlights the need for a new anti-tuberculosis drug. The cell wall of mycobacteria is characterised by high diaminopimelic acid (DAP) content—an intermediate of the (S)-lysine biosynthetic pathway and dihydrodipicolinate synthase (DHDPS) enzyme catalyses the first unique reaction of this biosynthesis. Interestingly, the gene knockout experiment demonstrates the essentiality of the DAP pathway, where the absence of DAP results in cell lysis and death. Because of this importance, any inhibitor of DHDPS enzyme may indicate a new class of anti-tubercular agent. In this perspective, the aim of the present study is to focus on the molecular docking analysis of DHDPS enzyme against the analogues of 2-methylheptyl isonicotinate—a compound having strong antibacterial property against Mycobacterium tuberculosis. The analogues used in the present study were retrieved from the NCBI PubChem database subject to Lipinski rule of five filters which would make the analogues like an orally active drug. Further, the top docked compounds at the active site of the DHDPS enzyme were analysed for ADME-Toxicity prediction.