Towards Antituberculosis Drugs: Molecular Docking of Curcumin and its Analogues to Pantothenate Synthetase
Catrina Theresa M. Yang1 and Junie B. Billones1,2*
1Department of Physical Sciences and Mathematics, College of Arts and Sciences, and 2Institute of Pharmaceutical Sciences, National Institutes of Health,
University of the Philippines Manila, Padre Faura, Ermita, Manila
corresponding author: This email address is being protected from spambots. You need JavaScript enabled to view it.
ABSTRACT
Pantothenate synthetase (PS), an enzyme that furnishes an essential precursor of coenzyme A, has been considered as potential target for novel antituberculosis agents. Hence, curcumin, a well-recognized multi-targeted natural product, and its analogues, have been docked to the enzyme. Curcumin analogue 3, having a hydroxyl and methoxy substituents in the aromatic moieties, exhibited the best binding interaction with PS. Its binding energy, as well as that of curcumin and two other analogues (16 and 18), suggests that these compounds are potentially more potent than nafronyl oxalate, a known inhibitor of the enzyme. Like the natural active intermediate, pantoyl adenylate, analogue 3 interacts with 3 amino acids in common: Gln72, Val187, and Met195. Moreover, its ketone oxygens were oriented directly towards the positive surface of the enzyme, providing additional polar interactions.
INTRODUCTION
Tuberculosis, commonly abbreviated as TB, is a bacterial disease caused by the infection of Mycobacterium tuberculosis (MTB) (Corbett et al. 2003). As an airborne disease, it is highly infectious. It afflicts millions of people each year and ranks as the world’s second leading cause of death from an infectious disease, after the human immuno-deficiency virus (HIV). According to World Health Organization (WHO), the estimated number of new cases in 2011 was almost 9 million with 1.4 million TB deaths (990 000 among HIV negative people and 430 000 HIV-associated TB deaths) (WHO 2012). In 2011, there were estimated 630 000 cases of multidrug resistant TB (MDR TB) while new cases of extensively drug resistant TB (XDR TB) is estimated at 40,000 in 2009 (Goldman & Laughon 2009). . . . . . . . . . . . .
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