Biological evaluation and structure-activity relationships of imidazole-based compounds as antiprotozoal agents
01 Pubblicazione su rivista
Saccoliti Francesco, Madia VALENTINA NOEMI, Tudino Valeria, DE LEO Alessandro, Pescatori Luca, Messore Antonella, DE VITA Daniela, Scipione Luigi, Brun Reto, Kaiser Marcel, Mäser Pascal, Magalhaes Calvet Claudia, K Jennings Gareth, M Podust Larissa, Costi Roberta, DI SANTO Roberto
ISSN: 0223-5234
We discovered a series of azole antifungal compounds as effective antiprotozoal agents. They displayed promising inhibitory activities within the micromolar-submicromolar range against P. falciparum, L. donovani, and T. b. rhodesiense. Moreover, most of such compounds showed excellent nanomolar IC50against T. cruzi, showing also very low cytotoxicity. Discussion of structure-activity relationships and biological data for these compounds are provided against the different parasites. To assess the mechanism of action against T. cruzi we proved that the most potent compounds (3b, 3j-l) inhibited the T. cruzi CYP51. Moreover, the most active derivative 3j dramatically reduced parasitemia in T. cruzi mouse model without acute toxicity.
AHRQMVNBLZIKPR-UHFFFAOYSA-N animals antifungal antileishmanial antiplasmodial Antiprotozoal Agents antitrypanosomal BHLRUOGOYQUJHE-UHFFFAOYSA-N BKAGEDZBILNZHR-UHFFFAOYSA-N BTKUBELCONMVFQ-UHFFFAOYSA-N Cell Line chagas disease CYP51 DBDGQVVQYMKPAS-UHFFFAOYSA-N DIYSLQICFHBTQL-UHFFFAOYSA-N Drug Discovery3003 Pharmaceutical Science DULCCGQQCJNKEM-UHFFFAOYSA-N Falciparum Female FXVBCYIZDNNSCJ-UHFFFAOYSA-N GDTOFSFBQOMDHZ-UHFFFAOYSA-N GGBXYXPRVQOMBV-UHFFFAOYSA-N Humans Imidazoles inhibitory concentration 50 JCDQIFZYGBRUER-UHFFFAOYSA-N JMNHBCQWFJFBQW-UHFFFAOYSA-N leishmania donovani leishmaniasis visceral malaria Mice Mice Inbred BALB C NBHPUKZRPYQEGR-UHFFFAOYSA-N Parasitic Sensitivity Tests PBNJEFLDXFIGNG-UHFFFAOYSA-N RGSRKBHTUUKVTA-UHFFFAOYSA-N Trypanosoma brucei rhodesiense Trypanosoma cruzi Trypanosomiasis African UEQSTADAVQNNDM-UHFFFAOYSA-N VOZKRUYNVQHSHL-UHFFFAOYSA-N VZFXJIQTDMSFFQ-UHFFFAOYSA-N YKBDGMCRYYLJKW-UHFFFAOYSA-N YXTSXRAOMZGEAR-UHFFFAOYSA-N zole