Ankita Srivastava* and Deepak Chandra Pages 145 - 155 ( 11 )
Background: The unsatisfactory treatment options for Visceral Leishmaniasis (VL), need identification of new drug targets. Among natural products, Alkaloids have been proved to be highly effective against number of diseases. In Leishmania, UDP-galactopyranosemutase (UGM) is a critical enzyme required for cell wall synthesis and thus a drug target for structure based drug designing against L. donovani.
Objective: The aim was to build the homology model of UDP galactopyransemutase and investigate the interaction of selected alkaloids with this modeled UDP galactopyranosemutase by molecular docking.
Methodology: Since no crystal structure record has been found with this protein, a homology modeling was performed and a three dimensional structure of L. donovani UGM was created using MODELLER v9.9, structure quality was validated using PROCHECK and QMEAN programs which confirms that the structure is reliable. Further Molecular docking was performed with previously reported15 alkaloids.
Results: It was found that Protopine with a binding energy of -12.39Kcal/mole, binds at Flavin adenine dinucleotide (FAD) biding site.
Conclusion: It was concluded that Protopine, an alkaloid could interrupt the functional aspect of L. donovani UGM and thus may be useful for drug designing studies. These finding would contribute to the understanding of the effect of drug on the parasite.
Leishmania, natural compounds, Alkaloids, drug target, homology modeling, docking antileishmanial, UGM.
Department of Biochemistry, Lucknow University, Lucknow, Uttar Pradesh, 226007, Department of Biochemistry, Lucknow University, Lucknow, Uttar Pradesh, 226007