ABSTRACT
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.
Subject(s)
Antinematodal Agents/chemical synthesis , Antitrichomonal Agents/chemical synthesis , Nematoda/drug effects , Quinolines/chemical synthesis , Trichomonas vaginalis/drug effects , Animals , Antinematodal Agents/pharmacology , Antitrichomonal Agents/pharmacology , Quinolines/pharmacology , Structure-Activity Relationship , Trichinella spiralis/drug effectsABSTRACT
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.
Subject(s)
Antinematodal Agents/chemical synthesis , Antinematodal Agents/pharmacology , Glycosides/chemical synthesis , Glycosides/pharmacology , Pteridines/chemical synthesis , Pteridines/pharmacology , Animals , Caenorhabditis elegans/drug effectsABSTRACT
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.
