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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Development of Novel Isoindolone-Based Compounds against Trypanosoma brucei rhodesiense

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Author(s):
Silva, Daniel G. [1, 2] ; Feijens, Pim-Bart [3] ; Hendrickx, Rik [3] ; Matheeussen, An [3] ; Grey, Lucie [4] ; Caljon, Guy [3] ; Maes, Louis [3] ; Emery, Flavio S. [1] ; Junker, Anna [2]
Total Authors: 9
Affiliation:
[1] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, QHeteM Lab Quim Heterocicl Med, BR-14040903 Ribeirao Preto, SP - Brazil
[2] Westphalian Wilhelms Univ Munster, European Inst Mol Imaging EIMI, D-48149 Munster - Germany
[3] Univ Antwerp, Lab Microbiol Parasitol & Hyg LMPH, Univ Pl 1, B-2610 Antwerp - Belgium
[4] Westphalian Wilhelms Univ Munster, Inst Pharmaceut & Med Chem, D-48149 Munster - Germany
Total Affiliations: 4
Document type: Journal article
Source: CHEMISTRYOPEN; v. 10, n. 9, p. 922-927, SEP 2021.
Web of Science Citations: 1
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 (IC(50)m) 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, absence of cytotoxicity and acceptable metabolic stability. However, the solubility of the compounds represents a limiting factor that should be addressed to improve the physicochemical properties that are required to proceed further in the development of in vivo-active derivatives. (AU)

FAPESP's process: 17/22001-0 - Synthesis and evaluation of new heterocyclic compounds as potential antitrypanosomal agents
Grantee:Daniel Gedder Silva
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 17/21146-4 - Heterocyclic chemistry and epigenetic for the development of library of compounds for medicinal chemistry purposes.
Grantee:Flavio da Silva Emery
Support Opportunities: Regular Research Grants