New 3-piperonylcoumarins as inhibitors of glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH) from Trypanosoma cruzi.
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.
de Marchi
Anderson Aparecido
AA
Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, 14040903 Ribeirão Preto, SP, Brazil.
Castilho
Marcelo Santos
MS
Nascimento
Paulo Gustavo Barboni
PG
Archanjo
Fernando Costa
FC
del Ponte
Gino
G
Oliva
Glaucius
G
Pupo
Mônica Tallarico
MT
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
D003374:Coumarins; D004791:Enzyme Inhibitors; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases