Cytotoxic Flavone Analogues of Vitexicarpin, a Constituent of the Leaves of Vitex negundo

• Published in: Journal of natural products (Washington, D.C.) Vol. 66; no. 6; pp. 865 - 867
• Main Authors: Díaz, Fredyc, Chávez, Daniel, Lee, Dongho, Mi, Qiuwen, Chai, Hee-Byung, Tan, Ghee T, Kardono, Leonardus B. S, Riswan, Soedarsono, Fairchild, Craig R, Wild, Robert, Farnsworth, Norman R, Cordell, Geoffrey A, Pezzuto, John M, Kinghorn, A. Douglas
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 01.06.2003; Amer Chemical Soc; American Society of Pharmacognosy
• Subjects: acetylation; Acylation; Animals; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - isolation & purification; Antineoplastic Agents, Phytogenic - pharmacology; Biological and medical sciences; cell lines; chemical structure; Chemistry, Medicinal; Colonic Neoplasms; cytotoxicity; Disease Models, Animal; Drug Screening Assays, Antitumor; flavones; Flavonoids - chemistry; Flavonoids - isolation & purification; Flavonoids - pharmacology; General pharmacology; Humans; Indonesia; Inhibitory Concentration 50; leaves; Leukemia P388; Life Sciences & Biomedicine; Lung Neoplasms; Male; Medical sciences; medicinal plants; Methylation; Mice; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Pharmacognosy. Homeopathy. Health food; Pharmacology & Pharmacy; Pharmacology. Drug treatments; phytochemicals; plant extracts; Plant Leaves - chemistry; Plant Sciences; Plants, Medicinal - chemistry; Prostatic Neoplasms; Science & Technology; spectral analysis; structure-activity relationships; Tumor Cells, Cultured - drug effects; Verbenaceae; Vitex - chemistry; Vitex negundo; vitexicarpin; Indonesia; Asia; MEDICINAL-PLANTS; ROTUNDIFOLIA; Antineoplastic agent; Cytotoxicity; Flavonoid; Medicinal plant; Folk medicine; Structure activity relation; Dicotyledones; Angiospermae; Tumor cell; Acylation; Human; Pharmacognosy; Oriental medicine; Rodentia; Plant leaf; Malignant tumor; In vitro; In vivo; Vertebrata; Chemical modification; Experimental disease; Mammalia; Cell line; Mouse; Verbenaceae; Animal; KB cell line; Plant origin; Flavone derivatives; Phenols; Isolation; Spermatophyta; Prostate
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np0300784

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.