Philippine Science Letters
vol. 5 | no. 2 | 2012
published online August 27, 2012


ARTICLE


Towards antituberculosis drugs: virtual screening for potential inhibitors of pantothenate synthetase of Mycobacterium tuberculosis


by Vivien Cherie C. Uy and Junie B. Billones*


Department of Physical Sciences and Mathematics, College of Arts and Sciences University of the Philippines Manila, Padre Faura, Ermita, Manila 1000 Philippines



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A structure-based pharmacophore has been generated based on the binding site of pantothenate synthetase. The pharmacophore was used to screen libraries of compounds for potential inhibitors of the enzyme. The top hit was compound NSC_125296 (2-hydroxy-3-[(2E)-1-(3-hydroxy- 1,4-dioxonaphthalen-2-yl)-3-phenylprop-2-en-1-yl]naphthalene- 1,4-dione) with binding energy that is over three times better than that of a known inhibitor nafronyl oxalate. Subsequent structural modification of NSC_125296 yielded compounds with better binding energies compared to that of native substrate pantoyl adenylate.

Email Address: jbbillones@upm.edu.ph
Submitted: June 7, 2012
Revised: July 4, 2012
Accepted: July 7, 2012
Published: August 27, 2012
Editor-in-charge: Gisela P. Padilla - Concepcion
Reviewers:
Baltazar D. Aguda
Len Herald V. Lim