Development of Novel Isoindolone-Based Compounds against Trypanosoma brucei rhodesiense.

ABSTRACT: This study identified the isoindolone ring as a scaffold for novel agents against Trypanosoma brucei rhodesiense and explored the structure-activity relationships of various aromatic ring substitutions. The compounds were evaluated in an integrated in vitro screen. Eight compounds exhibited selective activity against T. b. rhodesiense (IC₅₀ <2.2 μm) with no detectable side activity against T. cruzi and Leishmania infantum. Compound 20 showed low nanomolar potency against T. b. rhodesiense (IC₅₀ =40 nm) and no toxicity against MRC-5 and PMM cell lines and may be regarded as a new lead template for agents against T. b. rhodesiense. The isoindolone-based compounds have the potential to progress into lead optimization in view of their highly selective in vitro potency, ab

SUBMITTER: Silva DG 

PROVIDER: S-EPMC8459400 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature