title: Identification of electronic and structural descriptors of adenosine analogues related to inhibition of leishmanial glyceraldehyde-3-phosphate dehydrogenase.
abstract: Quantitative structure-activity relationship (QSAR) studies were performed in order to identify molecular features responsible for the antileishmanial activity of 61 adenosine analogues acting as inhibitors of the enzyme glyceraldehyde 3-phosphate dehydrogenase of Leishmania mexicana (LmGAPDH). Density functional theory (DFT) was employed to calculate quantum-chemical descriptors, while several structural descriptors were generated with Dragon 5.4. Variable selection was undertaken with the ordered predictor selection (OPS) algorithm, which provided a set with the most relevant descriptors to perform PLS, PCR and MLR regressions. Reliable and predictive models were obtained, as attested by their high correlation coefficients, as well as the agreement between predicted and experimental values for an external test set. Additional validation procedures were carried out, demonstrating that robust models were developed, providing helpful tools for the optimization of the antileishmanial activity of adenosine compounds.
authors: Instituto de Química de São Carlos, Universidade de São Paulo, São Carlos, SP 13566-590, Brazil.
authors: Norka B H
authors: NB
authors: Lozano
authors: Rafael F
authors: RF
authors: Oliveira
authors: Karen C
authors: KC
authors: Weber
authors: Kathia M
authors: KM
authors: Honorio
authors: Rafael V
authors: RV
authors: Guido
authors: Adriano D
authors: AD
authors: Andricopulo
authors: Albérico B F
authors: AB
authors: Da Silva
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000737:chemistry; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D007894:Leishmania mexicana / Q000201:enzymology*; D062105:Molecular Docking Simulation; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D000981:Antiprotozoal Agents; D015800:Protozoan Proteins; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D000241:Adenosine
references: J Med Chem. 1994 Oct 14;37(21):3605-13
references: 7932587
references: PLoS Negl Trop Dis. 2012;6(5):e1544
references: 22666507
references: J Med Chem. 1995 Sep 15;38(19):3838-49
references: 7562915
references: Comb Chem High Throughput Screen. 2006 Mar;9(3):213-28
references: 16533155
references: PLoS Negl Trop Dis. 2012;6(4):e1625
references: 22545171
references: SAR QSAR Environ Res. 1997;7(1-4):173-93
references: 9501508
references: J Med Chem. 2001 Jun 21;44(13):2080-93
references: 11405646
references: BMC Struct Biol. 2009 Feb 25;9:9
references: 19243605
references: J Chem Inf Model. 2008 Apr;48(4):918-29
references: 18303835
references: Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4273-8
references: 10200252
references: J Comput Aided Mol Des. 2004 Jul-Sep;18(7-9):587-96
references: 15729857
references: J Med Chem. 1998 Nov 19;41(24):4790-9
references: 9822549
references: J Comput Aided Mol Des. 2005 Jun;19(6):453-63
references: 16231203
references: Phys Rev B Condens Matter. 1988 Jan 15;37(2):785-789
references: 9944570
references: Bioinformatics. 2006 Jul 15;22(14):1710-6
references: 16632493
references: Trop Med Int Health. 2001 Nov;6(11):849-54
references: 11703838
references: Chem Rev. 1996 May 9;96(3):1027-1044
references: 11848779
references: Trop Med Int Health. 2009 Jun;14(6):639-44
references: 19392741
references: Eur J Med Chem. 2008 Feb;43(2):364-72
references: 17562349
references: J Chem Inf Comput Sci. 2002 May-Jun;42(3):682-92
references: 12086530
references: J Mol Biol. 2001 Jun 1;309(2):423-35
references: 11371162
references: J Comput Aided Mol Des. 2004 Jul-Sep;18(7-9):549-62
references: 15729854
references: Clin Microbiol Infect. 2011 Oct;17(10):1471-7
references: 21933305
references: J Mol Graph Model. 2002 Jan;20(4):269-76
references: 11858635
references: Science. 1983 Aug 19;221(4612):709-13
references: 6879170