Studies toward the structural optimization of new brazilizone-related trypanocidal 1,3,4-thiadiazole-2-arylhydrazone derivatives.
Megazol is a highly active compound against Trypanosoma cruzi, and has become a core structure for the design of new trypanocidal agents. Recently, we have identified the new potent trypanocide agent Brazilizone A, which presents an IC(50) twofold more potent than the prototype megazol. This result has encouraged us to further explore structurally-related 1,3,4-thiadiazole-2-arylhydrazone derivatives, in order to get a better understanding of their structural and antiprotozoal activity relationships. Herein we report the synthesis and trypanocidal profile of thirteen new Brazilizone A analogues, which supported the construction of 3D-QSAR models used for its structural optimization.
Carvalho
Samir A
SA
Fundação Oswaldo Cruz, Instituto de Tecnologia em Fármacos - Far-Manguinhos, Laboratório de Síntese IV, 21041-250 Rio de Janeiro, RJ, Brazil.
Lopes
Francisco A S
FA
Salomão
Kelly
K
Romeiro
Nelilma C
NC
Wardell
Solange M S V
SM
de Castro
Solange L
SL
da Silva
Edson F
EF
Fraga
Carlos A M
CA
D000818:Animals; D018360:Crystallography, X-Ray; D006835:Hydrazones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D021281:Quantitative Structure-Activity Relationship; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D014345:Trypanosoma / Q000187:drug effects
D006835:Hydrazones; D013830:Thiadiazoles; D014344:Trypanocidal Agents; C499674:brazilizone A