Synthesis of chalcone analogues with increased antileishmanial activity.
Eighteen analogues of an active natural chalcone were synthesized using xanthoxyline and some derivatives, and these analogues were tested for selective activity against both promastigotes and intracellular amastigotes of Leishmania amazonensis in vitro. Three analogues (10, 12, and 19) containing nitro, fluorine or bromine groups, respectively, displayed increased selective activity against the parasites as compared with the natural chalcone. The nitrosylated chalcone 10 was also tested intralesionally in infected mice and was found to be as effective as Pentostan reference drug at a dose 100 times higher than that of the chalcone in controlling both the lesion growth and the parasite burden.
Boeck
Paula
P
Universidade Federal de Santa Catarina, Departamento de Química, Campus Trindade, Florianópolis, Brazil.
Bandeira Falcão
Camila Alves
CA
Leal
Paulo César
PC
Yunes
Rosendo Augusto
RA
Filho
Valdir Cechinel
VC
Torres-Santos
Eduardo Caio
EC
Rossi-Bergmann
Bartira
B
D000098:Acetophenones / Q000737:chemistry*; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002599:Chalcone / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D007891:Leishmania / Q000187:drug effects*; D007896:Leishmaniasis / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D013997:Time Factors
D000098:Acetophenones; D000981:Antiprotozoal Agents; D002599:Chalcone; C064382:xanthoxyline