Antileishmanial activity screening of 5-nitro-2-heterocyclic benzylidene hydrazides.
A series of 53 nitro derivatives rationally designed were obtained by parallel synthesis and screened against Leishmania donovani. Six compounds exhibited IC(50) values lower than standard drugs. Brief SAR analysis revealed that substitution is important to the activity. Nitrothiophene analogues were more potent than the nitrofuran ones. This was attributed to the ability of sulfur atoms in accommodating electrons from nitro group, which facilitate its reduction and therefore the formation of free radicals lethal to parasites.
Faculdade de Ciências Farmacêuticas, Universidade de São Paulo-Av. Prof. Lineu Prestes, 580 CEP 05508-900, R. Afonso Celso, 718 apto 144 Vila Mariana, 04119-060 São Paulo, SP, Brazil. dgrando@usp.br
Daniela G
DG
Rando
Mitchell A
MA
Avery
Babu L
BL
Tekwani
Shabana I
SI
Khan
Elizabeth I
EI
Ferreira
D000818:Animals; D005609:Free Radicals; D006571:Heterocyclic Compounds / Q000737:chemistry* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007893:Leishmania donovani / Q000187:drug effects*; D009581:Nitrofurans; D013329:Structure-Activity Relationship; D013876:Thiophenes; D014344:Trypanocidal Agents / Q000737:chemistry* / Q000494:pharmacology
D005609:Free Radicals; D006571:Heterocyclic Compounds; D009581:Nitrofurans; D013876:Thiophenes; D014344:Trypanocidal Agents