Semisynthesis of new aphidicolin derivatives with high activity against Trypanosoma cruzi

Author(s)

Santos, Gabriela B. ^[1] ; Krogh, Renata ^[2] ; Magalhaes, Luma G. ^[2] ; Andricopulo, Adriano D. ^[2] ; Pupo, Monica T. ^[1] ; Emery, Flavio S. ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Lab Quim Med & Computac, BR-13560590 Sao Carlos, SP - Brazil

• Document type: Journal article
• Source: Bioorganic & Medicinal Chemistry Letters; v. 26, n. 4, p. 1205-1208, FEB 15 2016.
• Web of Science Citations: 7

Abstract

Chagas disease continues to be a difficult disease to eradicate, largely because of the widespread populations it affects as well as the highly toxic effects of current therapies. Thus, the exploration of innovative scaffolds, ideally with distinct mechanisms of action, is urgently needed. The natural product aphidicolin and its effects on cell cycle division have been widely studied; it is a potent inhibitor of parasitic cells. In the present study, we report for the first time the semisynthesis of a series of aphidicolin derivatives, their unique structural features, and demonstration of their activity against Trypanosoma cruzi cells. Two demonstrated high potency and selectivity against parasitic amastigote cells, and thus show promise as new leads for Chagas disease treatment. (C) 2016 Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
• Grantee: Glaucius Oliva
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 09/14184-0 - Antiinfective compounds: bringing together medicinal chemistry and organic synthesis in search of lead antiparasitic compounds
• Grantee: Flavio da Silva Emery
• Support Opportunities: Regular Research Grants