Non-competitive inhibitor of nucleoside hydrolase from Leishmania donovani identified by fragment-based drug discovery. Issue 90 (14th September 2016)

• Record Type: Journal Article
• Authors: Alves, M. A.; Nirma, C.; Moreira, M. M.; Soares, R. O.; Pascutti, P. G.; Noël, F.; Costa, P. R. R.; Sant'Anna, C. M. R.; Barreiro, E. J.; Lima, L. M.; Tinoco, L. W.
• Is Part Of: RSC advances. Volume 6:Issue 90(2016)
• Page Start: 87738
• Page End: 87744
• Publication Date: 2016-09-14
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c6ra15143d
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : New non-competitive inhibitor of nucleoside hidrolase from L. donovani identified by fragment-based drug discovery using STD NMR and molecular docking. Abstract : Nucleoside hydrolase is an important target for the development of new leishmanicidal agents due to its role in parasite proliferation. Using the principles of fragment-based drug discovery, a library of 111 fragments was assembled for screening by nuclear magnetic resonance using the saturation transfer difference. Five fragments were selected as ligands of Leishmania donovani nucleoside hydrolase (NH Ld ) and kinetics studies revealed that fragment3 acts as a new non-competitive inhibitor. Its binding mode was proposed on the basis of molecular docking, using a structural model of NH Ld constructed by homology. An intermolecular interaction between fragments3 and5 was found by NOESY and docking studies. These data could be used to design more potent NH Ld inhibitors and to aid the development of leishmanicidal drugs.