Abstract

Junie B. Billones*^1,2 and Ariane Marielle F. Valle¹

DOI : http://dx.doi.org/10.13005/ojc/300326

The emergence of Mycobacterium tuberculosis(Mtb) drug resistant strains calls for research of novel anti-TB drugs. In this study,structure-based pharmacophore generation, virtual screening, molecular docking and de novolead optimization were employed in the search for possible inhibitors of MaltosyltransferaseGlgE enzyme,a recently validated anti-TB drug target. Chemical libraries containing only natural products were screened. The top hits were docked and the resulting leads were subsequently modified usingDe Novo Evolution. Three modified compounds were found to have greaterbinding energy than the substrate. All were derived from the lead compound ZINC39010596 (5,7-dihydroxy-2-propan-2-yl-8-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxychromen-4-one). Toxicity predictions of these compounds revealed that they were non-carcinogenic, non-mutagenic, and biodegradable.

Tuberculosis; MaltosyltransferaseGlgE; Structure-based Pharmacophore Generation; Virtual Screening; Molecular Docking

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