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
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.
J Nat Prod. 2003 Jun;66(6):865-7. 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.
对黄荆叶氯仿可溶提取物进行生物测定导向的分级分离，得到了已知的黄酮类化合物牡荆素（1），该化合物在一组人癌细胞系中表现出广泛的细胞毒性。为了提高化合物1的细胞毒性效力，对该化合物进行了一系列酰化反应，以获得其甲基化产物（2）、乙酰化产物（3）以及六个新的酰化衍生物（4 - 9）。化合物9，即先前未报道的5,3'-二己酰氧基-3,6,7,4'-四甲氧基黄酮，表现出与化合物1相当的细胞毒性效力，并被选作进一步评估。然而，在体内中空纤维试验中，以最高测试剂量（40mg/kg体重）对Lu1、KB和LNCaP细胞进行评估时，以及在体内P - 388白血病模型（135mg/kg）中，采用腹腔注射途径给药时，发现该化合物无活性。
