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.

Estimation of Micronutrients in <i>Vitex negundo</i> L. (Karunochi) Leaves

“…and 135 mg/kg), exhibited cytotoxicity in a human cancer cell line panel [8].The anti-hyperglycemic effect of leaves due to iridoid glycoside was comparable with glibenclamide. It has significant productive effect on glycoprotein metabolism [9].…”

Molecular Mechanisms of Casticin Action: an Update on its Antitumor Functions

“…As shown in Figure 1, accumulated data indicate that casticin was isolated from many plant species such as, namely Vitex agnus castus (Choudhary et al, 2009;Mesaik et al, 2009;Webster et al, 2011;Righeschi et al, 2012;Hogner et al, 2013), Daphne genkwa (Xie et al, 2011), Achillea millefolium (Haidara et al, 2006;Csupor-Loffler et al, 2009), Ficus microcarpa , Vitex rotundifolia (Ono et al, 2002;Hu et al, 2007b;Shen et al, 2009;Ye et al, 2010;Koh et al, 2011), Fructus viticis (Hu et al, 2007b;Guan et al, 2010;Chen et al, 2011b;Yang et al, 2011;Zeng et al, 2012;Zhou et al, 2013a), Vitex negundo (Diaz et al, 2003;Kunwar et al, 2010;Velpandian et al, 2013), Crataegus pinnatifida (Kao et al, 2005), Pavetta crassipes (Mali and Dhake, 2011), Nelsonia canescens, Butea frondosa Koen , Dalbergia odorifera (Mali and Dhake, 2011), Bryonia laciniosa (Aggarwal et al, 2011), Citrus unshu (Mali and Dhake, 2011;Nagoor et al, 2011), Centipeda minima (Mali and Dhake, 2011), Clausena excavate (Manosroi et al, 2005), Croton betulaster (de Sampaio e Spohr et al, 2010;Freitas et al, 2011), Dimorphandra mollis (Freitas et al, 2011), Artemisia abrotanum L. (Hernandez et al, 1999), Artemisia annua L …”

“…It inhibited eosinophil migration and activity of chemokines and adhesion of molecules involved in the inflammatory process of asthma by suppressing the NF-κB pathway (Koh et al, 2011). Casticin's biological effects have been reported in wide spectrum of indications (Table 1), including inflammation (Lin et al, 2007b;Koh et al, 2011;Lee et al, 2012), asthma (Koh et al, 2011), tumor (Ono et al, 2002;Hu et al, 2007b;Shen et al, 2009;Ye et al, 2010;Koh et al, 2011), pre-menstrual syndrome (Hu et al, 2007b;Webster et al, 2011), immunomodulation (You et al, 1998), headache (Choudhary et al, 2009;Mesaik et al, 2009;Webster et al, 2011;Righeschi et al, 2012;Hogner et al, 2013), rheumatoid arthritis (You et al, 1998), conjunctivitis (Remberg et al, 2004), trachoma, gonorrhoea, and toothache (Diaz et al, 2003;Kunwar et al, 2010;Velpandian et al, 2013).…”

“…Casticin triggers antiproliferative effects and apoptosis in various cancer cells including human prostate (Diaz et al, 2003), colon (Tang et al, 2013), oral epidermoid carcinoma (Kobayakawa et al, 2004), breast cancer (Song et al, 2010), and leukemia cells (Diaz et al, 2003;Shen et al, 2009;Righeschi et al, 2012).…”

A Novel Clerodane Diterpene from <i>Vitex cofassus</i>

“…1) Terpenes, flavonoids, and lignans are the main constituents isolated from Vitex species. [2][3][4][5] Diverse pharmacological activities, including hepatoprotective, 6) antitumor, [7][8][9] antimicrobial, 2) antimutagenic, 10) anti-inflammatory, 11) anti-human immunodeficiency virus (HIV), 12) and antitubercular 13) activities, have also been reported. Vitex cofassus, native to New Guinea and the Southwest Pacific Islands, is an untouched plant, although a pharmaco-toxicological study of the crude extract of its bark was conducted in 1969.…”