RESUMEN
Several quinolines were synthesized and evaluated in vitro and in vivo against the nematodes Caenorhabditis elegans, Heligmosomoides polygyrus and the protozoa Trichomonas vaginalis. If some of them have shown in vitro nematocide activity (at 10 microM), however, their trichomonacidal activity reached 50% reduction at only 100 microM. The in vivo activity on Trichinella spiralis model was evaluated for some of the most in vitro active quinolines.
Asunto(s)
Antinematodos/síntesis química , Antitricomonas/síntesis química , Nematodos/efectos de los fármacos , Quinolinas/síntesis química , Trichomonas vaginalis/efectos de los fármacos , Animales , Antinematodos/farmacología , Antitricomonas/farmacología , Quinolinas/farmacología , Relación Estructura-Actividad , Trichinella spiralis/efectos de los fármacosRESUMEN
Albendazole (Abz) and Mebendazole (Mbz) analogues have been synthesized and in vitro tested against the protozoa Giardia lamblia, Trichomonas vaginalis and the helminths Trichinella spiralis and Caenorhabditis elegans. Results indicate that compounds 4a, 4b (Abz analogues), 12b and 20 (Mbz analogues) are as active as antiprotozoal agents as Metronidazole against G. lamblia. Compound 9 was 58 times more active than Abz against T. vaginalis. Compounds 8 and 4a also shown high activity against this protozoan. Compounds 4b and 5a were as active as Abz. None of the Mbz analogues showed activity against T. vaginalis. The anthelmintic activity presented by these compounds was poor.
Asunto(s)
Albendazol/análogos & derivados , Antiparasitarios/farmacología , Mebendazol/análogos & derivados , Albendazol/síntesis química , Albendazol/farmacología , Animales , Antiparasitarios/síntesis química , Caenorhabditis elegans/efectos de los fármacos , Giardia lamblia/efectos de los fármacos , Mebendazol/síntesis química , Mebendazol/farmacología , Metronidazol/uso terapéuticoRESUMEN
6,7-Diaryl derivatives of mono and di-S-glycopyranosylthiolumazine derivatives 5-8 were prepared to test their nematocide activity. In vitro tests against Caenorhabditis elegans were performed and it was found that monosubstituted derivatives 5-7 showed higher activity than the corresponding unsubstituted 2-thiolumazines 1-3, whilst 2-S,4-S-di-glycopyranosylpteridine derivative 8 was inactive in contrast to unsubstituted derivative 4. In order to check whether the lack of activity of 8 was due to the two bulky substituents of the pteridine nucleus, 2-S,4-S-dimethyl derivative 9 was synthesized and assayed showing also lack of activity. A theoretical study on the stability of the different possible tautomers of compound 4 was carried out in an attempt to explain some, in appearance, anomalous (13)C NMR data of this compound.