title: Synthesis, cytotoxicity, and anti-Trypanosoma cruzi activity of new chalcones.
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.
authors.affiliation: Department of Chemistry, University of Louisville, Louisville, Kentucky 40292, USA.
authors.forename: José C
authors.initials: JC
authors.lastname: Aponte
authors.forename: Manuela
authors.initials: M
authors.lastname: Verástegui
authors.forename: Edith
authors.initials: E
authors.lastname: Málaga
authors.forename: Mirko
authors.initials: M
authors.lastname: Zimic
authors.forename: Miguel
authors.initials: M
authors.lastname: Quiliano
authors.forename: Abraham J
authors.initials: AJ
authors.lastname: Vaisberg
authors.forename: Robert H
authors.initials: RH
authors.lastname: Gilman
authors.forename: Gerald B
authors.initials: GB
authors.lastname: Hammond
mesh_terms: 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*
chemical_list: D000981:Antiprotozoal Agents; D047188:Chalcones; D010936:Plant Extracts