Synthesis and in vitro evaluation of leishmanicidal and trypanocidal activities of N-quinolin-8-yl-arylsulfonamides.
In the present paper 12 N-quinolin-8-yl-arylsulfonamides synthesized by coupling 8-aminoquinolines with various arylsulfonylchlorides were assayed in vitro against Leishmania amazonensis, Leishmania chagasi and Trypanosoma cruzi strains. This series of new compounds were found to be selective for Leishmania spp. promastigote and amastigote forms. The most active compound was the N-(8-quinolyl)-3,5-difluoro-benzenesulfonamide 10 with an IC(50) against L. amazonensis and L. chagasi of 2.12 and 0.45 microM, respectively. The less cytotoxic biphenyl derivative 7 was very effective against intracellular L. amazonensis with a reduction of macrophage cell infection of 82.1% at 25 microM. In addition, a copper complex 17 of an inactive ligand was readily synthesized and showed high leishmanicidal and trypanocidal activity against both extra and intracellular forms.
da Silva
Luiz Everson
LE
Departamento de Química, Instituto de Ciências Exatas e da Terra, Universidade Federal de Mato Grosso, Cuiabá, 78060-900 Mato Grosso, Brazil.
Joussef
Antônio Carlos
AC
Pacheco
Letícia Kramer
LK
da Silva
Daniela Gaspar
DG
Steindel
Mário
M
Rebelo
Ricardo Andrade
RA
Schmidt
Boris
B
D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D003300:Copper / Q000737:chemistry; D020128:Inhibitory Concentration 50; D007891:Leishmania / Q000187:drug effects*; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D021261:Parasitic Sensitivity Tests; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000187:drug effects*; D015032:Zinc / Q000737:chemistry; D000096926:Benzenesulfonamides
D000981:Antiprotozoal Agents; D003300:Copper; D009942:Organometallic Compounds; D011804:Quinolines; D013449:Sulfonamides; D014344:Trypanocidal Agents; D015032:Zinc; C526466:N-(8-quinolyl)-3,5-difluoro-benzenesulfonamide; D000096926:Benzenesulfonamides