5-Vinylquinoline-substituted nitrofurans as inhibitors of trypanothione reductase and antitrypanosomal agents

Autor:	Jonas Šarlauskas, Diego Benítez, Narimantas Čėnas, Eglė Miliuvienė, Žilvinas Anusevičius, Marcelo A. Comini, Valė Miliukienė
Rok vydání:	2020
Předmět:	Chemistry medicine.drug_class medicine General Chemistry Trypanothione reductase Nitrofuran Combinatorial chemistry
Zdroj:	Chemija. 31
ISSN:	2424-4538 0235-7216
DOI:	10.6001/chemija.v31i2.4223
Popis:	Trypanothione reductase (TR) and trypanothione synthase (TS) are critical for the maintenance of thiol-redox homeostasis and antioxidant protection in trypanosomal parasites, which cause African sleeping sickness and Chagas disease. Both enzymes are absent in mammals. Thus, the design of efficient and specific TR and TS inhibitors represents one of the pathways for a development of new antitrypanosomal drugs. 5-Vinylquinoline-substituted nitrofurans (n = 7), studied in this work, acted as un- or noncompetitive to trypanothione inhibitors of Trypanosoma congolense TR. Their inhibition constants (Ki) varied from 2.3 µM to 150 µM. We for the first time observed a parallelism between their antitrypanosomal in vitro activity and their efficacy as TR inhibitors. The inhibition of TS appears not to be a significant factor of trypanocidal activity of examined compounds.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::4e89cf2ef377ee13aac84f2efdcd0bed https://doi.org/10.6001/chemija.v31i2.4223 Zobrazit plný text záznamu