Design, synthesis, electrochemistry and anti-trypanosomatid hit/lead identification of nitrofuranylazines.

Autor:	Saayman M; Centre of Excellence for Pharmaceutical Sciences, North-West University Potchefstroom 2520 South Africa David.Nda@nwu.ac.za +27 18 299 4243 +27 18 299 2256., Kannigadu C; Centre of Excellence for Pharmaceutical Sciences, North-West University Potchefstroom 2520 South Africa David.Nda@nwu.ac.za +27 18 299 4243 +27 18 299 2256., Aucamp J; Centre of Excellence for Pharmaceutical Sciences, North-West University Potchefstroom 2520 South Africa David.Nda@nwu.ac.za +27 18 299 4243 +27 18 299 2256., Janse van Rensburg HD; Centre of Excellence for Pharmaceutical Sciences, North-West University Potchefstroom 2520 South Africa David.Nda@nwu.ac.za +27 18 299 4243 +27 18 299 2256., Joseph C; Molecular Sciences Institute, School of Chemistry, University of the Witwatersrand Johannesburg-Braamfontein 2050 South Africa., Swarts AJ; Molecular Sciences Institute, School of Chemistry, University of the Witwatersrand Johannesburg-Braamfontein 2050 South Africa., N'Da DD; Centre of Excellence for Pharmaceutical Sciences, North-West University Potchefstroom 2520 South Africa David.Nda@nwu.ac.za +27 18 299 4243 +27 18 299 2256.
Jazyk:	angličtina
Zdroj:	RSC medicinal chemistry [RSC Med Chem] 2023 Aug 16; Vol. 14 (10), pp. 2012-2029. Date of Electronic Publication: 2023 Aug 16 (Print Publication: 2023).
DOI:	10.1039/d3md00220a
Abstrakt:	Chagas disease and leishmaniasis are vector-borne infectious diseases affecting both humans and animals. These neglected tropical diseases can be fatal if not treated. Hundreds to thousands of new Chagas disease and leishmaniasis cases are being reported by the WHO every year, and currently available treatments are insufficient. Severe adverse effects, impractical administrations and increased pathogen resistance against current clinical treatments underscore a serious need for the development of new drugs to curb these ailments. In search for such drugs, we investigated a series of nitrofuran-based azine derivatives. Herein, we report the design, synthesis, electrochemistry, and biological activity of these derivatives against promastigotes and amastigotes of Leishmania major , and L. donovani strains, as well as epimastigotes and trypomastigotes of Trypanosoma cruzi . Two leishmanicidal early leads and one trypanosomacidal hit with submicromolar activity were uncovered and stand for further in vivo investigation in the search for new antitrypanosomatid drugs. Future objective will focus on the identification of involved biological targets with the parasites. Competing Interests: The authors have no conflicts to declare. (This journal is © The Royal Society of Chemistry.)
Databáze:	MEDLINE
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