Structure-activity relationship of antileishmanials neolignan analogues.
Twenty-two synthetic analogues of neolignans comprising beta-ketoethers and beta-ketosulfides were obtained from condensation reactions among beta-bromoketones and phenols or thiophenols, respectively, in basic solutions, and assayed in vitro for activity against intracellular Leishmania amazonensis and Leishmania donovani amastigotes, the causative agents of cutaneous and visceral leishmaniasis. The highest selective activity was found for compounds with sulfur bridges, whereas beta-ketosulphoxides and beta-ketosulphones had significantly less growth inhibitory activity. Compounds 2-[(4-chlorophenyl)thio]propan-1-one and 1-(3,4-dimethoxy)-2-[(4-methylphenyl)thio]propan-1-one were the most potent, inhibiting the growth parasite species by over 90% at microgram/mL, but only compound 1-(3,4-dimethoxy)-2-[(4-methylphenyl)thio]propan-1-one was selectively toxic to the parasites.
Aveniente
Mário
M
Instituto de Química, Universidade Estadual de Campinas, UNICAMP, CP 6154, CEP l3083-970 Campinas, SP, Brazil.
Pinto
Eduardo F
EF
Santos
Lourivaldo S
LS
Rossi-Bergmann
Bartira
B
Barata
Lauro E S
LE
D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D004195:Disease Models, Animal; D007891:Leishmania / Q000187:drug effects*; D007896:Leishmaniasis / Q000188:drug therapy; D017705:Lignans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D013045:Species Specificity; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000981:Antiprotozoal Agents; D017705:Lignans