title: New 3-piperonylcoumarins as inhibitors of glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH) from Trypanosoma cruzi.
abstract: This article describes the synthesis and inhibitory activities of a series of new 3-piperonylcoumarins, designed as inhibitors of glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH) from Trypanosoma cruzi. The design was based on the structures of previously identified natural products hits. The most active synthesized derivatives contain heterocyclic rings at position 6. SAR studies, performed by electronic indices methodology (EIM), clustered the molecules in different groups due to the chemical substitutions regarding the biological activity. Molecular modeling studies by docking suggested a different binding mode for the most active derivatives, when compared to natural hit chalepin. Moreover, the coumarin ring seems to act only as a spacer group.
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, 14040903 Ribeirão Preto, SP, Brazil.
authors.forename: Anderson Aparecido
authors.initials: AA
authors.lastname: de Marchi
authors.forename: Marcelo Santos
authors.initials: MS
authors.lastname: Castilho
authors.forename: Paulo Gustavo Barboni
authors.initials: PG
authors.lastname: Nascimento
authors.forename: Fernando Costa
authors.initials: FC
authors.lastname: Archanjo
authors.forename: Gino
authors.initials: G
authors.lastname: del Ponte
authors.forename: Glaucius
authors.initials: G
authors.lastname: Oliva
authors.forename: Mônica Tallarico
authors.initials: MT
authors.lastname: Pupo
mesh_terms: D000818:Animals; D003374:Coumarins / Q000737:chemistry* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008830:Microbodies / Q000187:drug effects / Q000201:enzymology; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000201:enzymology
chemical_list: D003374:Coumarins; D004791:Enzyme Inhibitors; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases