title: Cytotoxic flavone analogues of vitexicarpin, a constituent of the leaves of Vitex negundo.
abstract: Bioassay-guided fractionation of the chloroform-soluble extract of the leaves of Vitex negundo led to the isolation of the known flavone vitexicarpin (1), which exhibited broad cytotoxicity in a human cancer cell line panel. In an attempt to increase the cytotoxic potency of 1, a series of acylation reactions was performed on this compound to obtain its methylated (2), acetylated (3), and six new acylated (4-9) derivatives. Compound 9, the previously unreported 5,3'-dihexanoyloxy-3,6,7,4'-tetramethoxyflavone, showed comparative cytotoxic potency to compound 1 and was selected for further evaluation. However, this compound was found to be inactive when evaluated in the in vivo hollow fiber assay with Lu1, KB, and LNCaP cells at the highest dose (40 mg/kg/body weight) tested, and in the in vivo P-388 leukemia model (135 mg/kg), using the ip administration route.
authors.affiliation: Program for Collaborative Research in the Pharmaceutical Sciences and Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Fredyc
authors.initials: F
authors.lastname: Díaz
authors.forename: Daniel
authors.initials: D
authors.lastname: Chávez
authors.forename: Dongho
authors.initials: D
authors.lastname: Lee
authors.forename: Qiuwen
authors.initials: Q
authors.lastname: Mi
authors.forename: Hee-Byung
authors.initials: HB
authors.lastname: Chai
authors.forename: Ghee T
authors.initials: GT
authors.lastname: Tan
authors.forename: Leonardus B S
authors.initials: LB
authors.lastname: Kardono
authors.forename: Soedarsono
authors.initials: S
authors.lastname: Riswan
authors.forename: Craig R
authors.initials: CR
authors.lastname: Fairchild
authors.forename: Robert
authors.initials: R
authors.lastname: Wild
authors.forename: Norman R
authors.initials: NR
authors.lastname: Farnsworth
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Cordell
authors.forename: John M
authors.initials: JM
authors.lastname: Pezzuto
authors.forename: A Douglas
authors.initials: AD
authors.lastname: Kinghorn
mesh_terms: D000215:Acylation; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D003110:Colonic Neoplasms; D004195:Disease Models, Animal; D004354:Drug Screening Assays, Antitumor; D005419:Flavonoids / Q000737:chemistry* / Q000302:isolation & purification* / Q000494:pharmacology; D006801:Humans; D007214:Indonesia; D020128:Inhibitory Concentration 50; D007941:Leukemia P388; D008175:Lung Neoplasms; D008297:Male; D008745:Methylation; D051379:Mice; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D018515:Plant Leaves / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D011471:Prostatic Neoplasms; D014407:Tumor Cells, Cultured / Q000187:drug effects; D020950:Vitex / Q000737:chemistry*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D005419:Flavonoids; C054133:casticin