Synthesis, cytotoxicity, and anti-Trypanosoma cruzi activity of new chalcones.
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.
Aponte
José C
JC
Department of Chemistry, University of Louisville, Louisville, Kentucky 40292, USA.
Verástegui
Manuela
M
Málaga
Edith
E
Zimic
Mirko
M
Quiliano
Miguel
M
Vaisberg
Abraham J
AJ
Gilman
Robert H
RH
Hammond
Gerald B
GB
D016475:3T3 Cells; D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D047188:Chalcones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D026324:Myristicaceae / Q000737:chemistry; D021261:Parasitic Sensitivity Tests; D010936:Plant Extracts / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010946:Plants, Medicinal / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014349:Trypanosoma cruzi / Q000187:drug effects*
D000981:Antiprotozoal Agents; D047188:Chalcones; D010936:Plant Extracts