Thiophene derivatives activity against the protozoan parasite Leishmania infantum.

ABSTRACT: Treatments against leishmaniasis are limited and the development of new molecules is crucial. One class of developmental drug that has shown activity against the parasite Leishmania are thiophene derivatives. Here we synthetized thirty-eight novel thiophene compounds and characterized their activity and potential for resistance against L. infantum. Half of the molecules had an EC₅₀ in the low micromolar range, the piperidine derivatives being more potent than the tetramethylpyran derivatives. Resistance was challenging to select for, and resistant cells could only be raised against one (GC1-19) of the four most active compounds. Using chemogenomic screens we show that a gene conversion event at the ABCG2 locus as well as the overexpression of a tryparedoxin peroxidase are respon

SUBMITTER: Bigot S 

PROVIDER: S-EPMC9772499 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature