Virtual Screening Against M. tuberculosis 7,8-Diaminopelargonic Acid Synthase (MtbBioA) and In Silico Toxicity Evaluation of Top Hits

Author(s): Junie Billones, Maria C. Carrillo, Voltaire Organo, Stephani J. Macalino, Inno Emnacen, Jamie B. Sy.

Journal Name: Current Enzyme Inhibition

Volume 10 , Issue 2 , 2014

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Abstract:

Tuberculosis (TB) remains to be one of the major public health concerns worldwide. The continuing emergence of Mtb strains resistant to known drugs makes the campaign for successful TB control and treatment very difficult to accomplish. It is therefore imperative to search for newer chemical entities that could inhibit the growing number of putative drug targets for the development of more efficient anti-tubercular drugs. One such ideal target is the 7, 8- diaminopelargonic acid aminotransferase enzyme (BioA). This enzyme is mainly involved in the bacterium’s lipid biosynthesis and metabolism machinery, and is considered as a very promising target due to the fact that humans lack this enzyme. In this study, structure-based pharmacophore screening, molecular docking, and ADMET evaluation of compounds obtained from the InterBioScreen Synthetic Compounds (IBS SC) were performed against the MtbBioA enzyme. Five compounds from the library showed more favorable binding energies as compared to the enzyme’s known inhibitor, amiclenomycin (ACM). Moreover, a pyridazinyladamantane 2-carboxylic acid and two sulfone derivatives have indicated good ADMET properties. These compounds are predicted to possess desirable properties of a lead and should be the subject of subsequent structural optimization and experimental bioactivity evaluations.

Keywords: ADMET, DAPA, 7, 8-Diaminopelargonic acid synthase (BioA), 7-Keto-8-aminopelargonic acid (KAPA), molecular docking, Mycobacterium tuberculosis (Mtb), pharmacophore, virtual screening.

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Article Details

VOLUME: 10
ISSUE: 2
Year: 2014
Page: [105 - 112]
Pages: 8
DOI: 10.2174/1573408010666140922222427
Price: $58

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