QSAR Studies on NTF1836 Analogues as Mycothiol Biosynthesis Inhibitors

Author(s): M.K. Kathiravan*, S.S. Nilewar, A.N. Kale.

Journal Name: Letters in Drug Design & Discovery

Volume 15 , Issue 1 , 2018

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Abstract:

Background: Mycothiol (MSH), a thiol compound found in Mycobacterium tuberculosis is required for the growth and survival of bacteria. This unusual compound is found only in actinomycetes. MSH biosynthesis involves many enzymes, one of them is MshC an essential enzyme for M. tuberculosis.

Methods: NTF1836 were the first MSH biosynthesis inhibitors identified. QSAR studies were performed on a novel series of NTF1836 as an inhibitor of MshC (enzyme involved in the synthesis of mycothiol). The series of molecules were subjected to CoMFA, CoMSIA and HQSAR studies.

Results: The resulted model exhibited good correlation coefficient (r2) of 0.98, 0.87, 0.81 and cross validated correlation coefficient (q2) of 0.76, 0.60, and 0.61 for CoMFA, CoMSIA and HQSAR methods respectively. Contour map analysis revealed the importance of steric, electrostatic, donor, acceptor and hydrophobic fields in determining the activity.

Conclusion: The results of our structure activity relationships study reveals key contribution and can serve as a basis for future drug development of antitubercular agent.

Keywords: Mycothiol, NTF1836, M. tuberculosis, HQSAR, CoMFA, CoMSIA.

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Article Details

VOLUME: 15
ISSUE: 1
Year: 2018
Page: [3 - 14]
Pages: 12
DOI: 10.2174/1570180814666170823163045

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