Cytotoxic flavone analogues of vitexicarpin, a constituent of the leaves of Vitex negundo.
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.
Díaz
Fredyc
F
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.
Chávez
Daniel
D
Lee
Dongho
D
Mi
Qiuwen
Q
Chai
Hee-Byung
HB
Tan
Ghee T
GT
Kardono
Leonardus B S
LB
Riswan
Soedarsono
S
Fairchild
Craig R
CR
Wild
Robert
R
Farnsworth
Norman R
NR
Cordell
Geoffrey A
GA
Pezzuto
John M
JM
Kinghorn
A Douglas
AD
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*
D000972:Antineoplastic Agents, Phytogenic; D005419:Flavonoids; C054133:casticin