Discovery of highly potent and selective antiparasitic new oxadiazole and hydroxy-oxindole small molecule hybrids
| Autor: | Leonardo L. G. Ferreira, Manoel T. Rodrigues, Lucas A. Zeoly, Renata Krogh, Samia R. Lima, Fernando Coelho, Hugo Santos, Fábio S. Fernandes, Caroline Conti, Adriano D. Andricopulo |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Chagas disease
Antiparasitic medicine.drug_class Trypanosoma cruzi Oxadiazole 01 natural sciences Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound Parasitic Sensitivity Tests DOENÇA DE CHAGAS parasitic diseases Drug Discovery medicine Humans Oxindole Leishmania infantum 030304 developmental biology Pharmacology Oxadiazoles 0303 health sciences Molecular Structure biology 010405 organic chemistry Organic Chemistry Hep G2 Cells General Medicine medicine.disease biology.organism_classification Trypanocidal Agents Antiparasitic agent Oxindoles 0104 chemical sciences chemistry Biochemistry Benznidazole medicine.drug |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| ISSN: | 0223-5234 |
| Popis: | A series of highly active hybrids were discovered as novel antiparasitic agents. Two heterocyclic scaffolds (1,2,4-oxadiazole and 3-hydroxy-2-oxindole) were linked, and the resulting compounds showed in vitro activities against intracellular amastigotes of two protozoan parasites, Trypanosoma cruzi and Leishmania infantum. Their cytotoxicity was assessed using HFF-1 fibroblasts and HepG2 hepatocytes. Compounds 5b, 5d, 8h and 8o showed selectivity against L. infantum (IC50 values of 3.89, 2.38, 2.50 and 2.85 μM, respectively). Compounds 4c, 4q, 8a and 8k were the most potent against T. cruzi, exhibiting IC50 values of 6.20, 2.20, 2.30 and 2.20 μM, respectively. Additionally, the most potent anti-T. cruzi compounds showed in vitro efficacies comparable or superior to that of benznidazole. These easy-to-synthesize molecules represent novel chemotypes for the design of potent and selective lead compounds for Chagas disease and leishmaniasis drug discovery. |
| Databáze: | OpenAIRE |
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