Synthesis and Evaluation of Trypanocidal Activity of Chromane-Type Compounds and Acetophenones

• Published in: Molecules (Basel, Switzerland) Vol. 26; no. 23; p. 7067
• Main Authors: González, Luis A, Robledo, Sara, Upegui, Yulieth, Escobar, Gustavo, Quiñones, Wiston
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 23-11-2021; MDPI
• Subjects: Acetophenones - chemical synthesis; Acetophenones - pharmacology; Benznidazole; Bioavailability; Biological activity; Biological Products - chemical synthesis; Biological Products - pharmacology; Cell Survival - drug effects; Chagas disease; Chagas Disease - metabolism; Chagas Disease - parasitology; Chalcones - chemical synthesis; Chalcones - pharmacology; chromane; Chromatography; Chromones - chemical synthesis; Chromones - pharmacology; Cytotoxicity; Drug development; Drug Discovery - methods; Flavones; Flavones - chemical synthesis; Flavones - pharmacology; Humans; Natural products; Nifurtimox; Parasites; phenolic compounds; Phenols; prenyl derivatives; Selectivity; Toxicity; Trypanocidal Agents - chemical synthesis; Trypanocidal Agents - pharmacology; Trypanocides; Trypanosoma cruzi; Trypanosoma cruzi - drug effects; Trypanosomiasis; U937 Cells; Vaccines; Vector-borne diseases; United States > US; Germany; phenolic compounds; chromane; prenyl derivatives; Trypanosoma cruzi
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules26237067

American trypanosomiasis (Chagas disease) caused by the
parasite, is a severe health problem in different regions of Latin America and is currently reported to be spreading to Europe, North America, Japan, and Australia, due to the migration of populations from South and Central America. At present, there is no vaccine available and chemotherapeutic options are reduced to nifurtimox and benznidazole. Therefore, the discovery of new molecules is urgently needed to initiate the drug development process. Some acetophenones and chalcones, as well as chromane-type substances, such as chromones and flavones, are natural products that have been studied as trypanocides, but the relationships between structure and activity are not yet fully understood. In this work, 26 compounds were synthesized to determine the effect of hydroxyl and isoprenyl substituents on trypanocide activity. One of the compounds showed interesting activity against a resistant strain of
, with a half effective concentration of 18.3 µM ± 1.1 and an index of selectivity > 10.9.