Synthesis and structure-activity relationship of Trypanocidal lignans

• Grant number: 99/11738-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: February 01, 2000
• End date: April 30, 2001
• Field of knowledge: Physical Sciences and Mathematics - Chemistry
• Principal Investigator: Massuo Jorge Kato
• Grantee: Kenichi Nihei
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 98/05074-0 - Conservation and sustainable use of the plant biodiversity from the Cerrado and the Atlantic Forest: chemical diversity and prospecting for potential drugs, AP.BTA.TEM

Abstract

The Chagas' disease is a serious public health problem in the tropics and subtropics of continental America. Treatment by extremely effective drug at the early stage of the disease would lead not only to the alleviation of inflammation in acute stage, but also to the avoidance of dreadful lesion in chronic stage. However, several drugs in use cause severe side effects and are not efficient at the chronic stage. Recently, two highly trypanocidal tetrahydrofuran lignans, (+)-veraguensin and (-)-grandisin have been isolated from Virola surinamesis, a common tree in the Amazon Forest. The major aim in this project is to synthesize several analogs of tetrahydrofuran lignans, specially by means of radical cyclization of cinnamic ester and propargyl alcohol, in which a wide flexibility in the stereochemical control is achievable. Having several analogs, it will be possible to investigate the structure-activity relationship and mode of action on trypanocidal activity. Further improvement in the activity would lead to development of a highly effective therapeutic agent. (AU)