Abstract
Synthesis of a cytotoxic dihydrochalcone, first isolated from a traditional Amazonian medicinal plant Iryanthera juruensis Warb (Myristicaceae), followed by a comprehensive SAR analysis of saturated and unsaturated chalcone synthetic intermediates, led to the identification of analogues with selective and significant in vitro anti- Trypanosoma cruzi activity. Further SAR studies were undertaken with the synthesis of 21 new chalcones containing two allyloxy moieties that resulted in the discovery of 2',4'-diallyloxy-6'-methoxy chalcones with improved selectivity against this parasite at concentrations below 25 microM, four of which exhibited a selectivity index greater than 12.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
-
3T3 Cells
-
Animals
-
Antiprotozoal Agents / chemical synthesis*
-
Antiprotozoal Agents / chemistry
-
Antiprotozoal Agents / pharmacology*
-
Cell Line, Tumor
-
Cell Proliferation / drug effects
-
Chalcones / chemical synthesis*
-
Chalcones / chemistry
-
Chalcones / pharmacology*
-
Dose-Response Relationship, Drug
-
Drug Screening Assays, Antitumor
-
Fibroblasts / drug effects
-
Humans
-
Mice
-
Mice, Inbred BALB C
-
Molecular Structure
-
Myristicaceae / chemistry
-
Parasitic Sensitivity Tests
-
Plant Extracts / chemical synthesis
-
Plant Extracts / chemistry
-
Plant Extracts / pharmacology
-
Plants, Medicinal / chemistry
-
Stereoisomerism
-
Structure-Activity Relationship
-
Trypanosoma cruzi / drug effects*
Substances
-
Antiprotozoal Agents
-
Chalcones
-
Plant Extracts