Synthesis of 2-hydrazolyl-4-thiazolidinones based on multicomponent reactions and biological evaluation against Trypanosoma Cruzi.
A series of 18 novel 2-hydrazolyl-4-thiazolidinones-5-carboxylic acids, amides and 5,6-α,β-unsaturated esters were synthesized, and their in vitro activity on cruzipain and T. cruzi epimastigotes was determined. Some agents show activity at 37 μm concentration in the enzyme assay. Computational tools and docking were used to correlate the biological response with the physicochemical parameters of the compounds and their cruzipain inhibitory effects.
Departamento de Química Orgánica, Cátedra de Química Farmacéutica, Universidad de la República (UdelaR), Avda. General Flores 2124, CC1157 Montevideo, Uruguay.
Chiara
C
Pizzo
Cecilia
C
Saiz
Alan
A
Talevi
Luciana
L
Gavernet
Pablo
P
Palestro
Carolina
C
Bellera
Luis Bruno
LB
Blanch
Diego
D
Benítez
Juan J
JJ
Cazzulo
Agustina
A
Chidichimo
Peter
P
Wipf
S Graciela
SG
Mahler
D000081:Acetamides / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D001665:Binding Sites; D020134:Catalytic Domain; D002522:Chlorocebus aethiops; D003198:Computer Simulation; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000378:metabolism; D015800:Protozoan Proteins; D021281:Quantitative Structure-Activity Relationship; D053778:Thiazolidines / Q000737:chemistry*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000201:enzymology; D014709:Vero Cells
D000081:Acetamides; D000981:Antiprotozoal Agents; D015800:Protozoan Proteins; D053778:Thiazolidines; C030686:acetamide; D003546:Cysteine Endopeptidases; C063214:cruzipain