In Silico Studies of Quinoxaline-2-Carboxamide 1,4-di-N-Oxide Derivatives as Antimycobacterial Agents

Awwad Radwan,Wael Abdel-Mageed

doi:10.3390/molecules19022247

Awwad Radwan, Wael Abdel-Mageed

Open Access

https://doi.org/10.3390/molecules19022247

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Abstract

Molecular modelling studies were performed on some previously reported novel quinoxaline-2-carboxamide 1,4-di-N-oxide derivatives (series 1–9). Using the LigandScout program, a pharmacophore model was developed to further optimize the antimycobacterial activity of this series of compounds. Using the Dock6 program, docking studies were performed in order to investigate the mode of binding of these compounds. The molecular modeling study allowed us to confirm the preferential binding mode of these quinoxaline-2-carboxamide 1,4-di-N-oxide derivatives inside the active site. The obtained binding mode was as same as that of the novobiocin X-ray structure.

Highlights

Tuberculosis (TB) is the most prevalent infectious bacterial disease caused by Mycobacterium tuberculosis
Based on the assumption that the active compounds bind in a similar fashion at the active site, the Ligandscout program [19,20,21] was employed to evaluate the common features essential for antiproliferative activity and the hypothetical geometries adopted by these ligands in their most active forms
These compounds were submitted for pharmacophore model generation based on the shared chemical features

Summary

Introduction

Tuberculosis (TB) is the most prevalent infectious bacterial disease caused by Mycobacterium tuberculosis (mtb). A leading killer, tuberculosis is an intracellular infection responsible for some 3 million deaths annually, with a person lost to mtb every 15 s [1]. Spreading from person to person, and showing bad resistance to isoniazide and rifamicin, multidrug-resistant strains of M. tuberculosis (MDRTB) will necessarily make the future control of TB more difficult. This dilemma was worsened by the emergence of XDR-TB, that is unresponsive to isoniazid and rifampicin, the first line drugs, and to a fluoroquinolone and to at least one of the second-line drugs (amikacin, capreomycin or kanamycin) [2]

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