High selective leishmanicidal activity of 3-hydroxy-2-methylene-3-(4-bromophenyl)propanenitrile and analogous compounds.
Sixteen not new aromatic compounds were prepared by one-pot reaction i.e. through Baylis-Hillman reaction and were the first time evaluated against promastigote Leishmania amazonensis and infected mammalian cells. Most of the compounds were selectively more active against amastigotes than the reference drug sodium stibogluconate (Pentostam, IC(50)=44.7 microM). We found that 3-hydroxy-2-methylene-3-(4-bromophenyl) propanenitrile (13) was the most active (IC(50)=12.5 microM) and safer compound (0.0 (0.9); % macrophage LDH release), being the lead compound.
de Souza
R O M A
RO
Núcleo de Pesquisas de Produtos Naturais, Universidade Federal do Rio de Janeiro, Bloco H, CCS, Ilha do Fundão, Rio de Janeiro, RJ 21941-590, Brazil.
Pereira
V L P
VL
Muzitano
M F
MF
Falcão
C A B
CA
Rossi-Bergmann
B
B
Filho
E B A
EB
Vasconcellos
M L A A
ML
D000818:Animals; D066298:In Vitro Techniques; D007891:Leishmania / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000469:parasitology; D051379:Mice; D009570:Nitriles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
C519321:3-hydroxy-2-methylene-3-(4-bromophenyl)propanenitrile; D009570:Nitriles; D014344:Trypanocidal Agents