VOLUME 5 NUMBER 2 (July to December 2012)

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

A structure-based pharmacophore has been generated based on the binding site ofpantothenate synthetase. The pharmacophorewas used to screen libraries of compounds forpotential inhibitors of the enzyme. The top hitwas 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 betterthan that of a known inhibitor nafronyl oxalate. Subsequentstructural modification of NSC_125296 yielded compounds withbetter binding energies compared to that of native substratepantoyl adenylate.