Novel antitumor agents from higher plants

被引:47
作者
Lee, KH [1 ]
机构
[1] Univ N Carolina, Div Med Chem & Nat Prod, Sch Pharm, Nat Prod Lab, Chapel Hill, NC 27599 USA
关键词
cytotoxic plant-derived natural products; bioactivity-directed fractionation and; isolation; lead-identification and structural-modification studies;
D O I
10.1002/(SICI)1098-1128(199911)19:6<569::AID-MED7>3.0.CO;2-9
中图分类号
R914 [药物化学];
学科分类号
100701 [药物化学];
摘要
This review article describes research on cytotoxic natural products isolated from plant sources, primarily preclinical lead identification and structural modification studies performed in the Natural Products Laboratory of Dr. K, H. Lee. As a result of this work, more than 100 new cytotoxic antitumor compounds and their synthetic analogs have shown confirmed activity in NCI's in vitro human tumor cell lines bioassay and are of current interest to NCI for further in vivo evaluation. A significant and ongoing project involves novel antitumor analogs related to podophyllotoxin and etoposide, and has led to a potent derivative designated GL331 (17). This compound is currently in Phase IIa clinical trials and shows promise as an anticancer drug, especially for drug-resistant cancers. Bioactivity-directed fractionation and isolation of medicinal herbs (primarily herbs of Chinese origin) have also led to many classes of cytotoxic compounds including polyphenolic compounds, sesquiterpene lactones, lignans, quassinoids, triterpene glucosides, flavonoids, colchicine derivatives, and quinone derivatives. (C) 1999 John Wiley & Sons, inc.
引用
收藏
页码:569 / 596
页数:28
相关论文
共 86 条
[1]
[Anonymous], STUD NAT PROD CHEM
[2]
STRUCTURE-ACTIVITY-RELATIONSHIPS OF DIMERIC CATHARANTHUS ALKALOIDS .1. DEACETYLVINBLASTINE AMIDE (VINDESINE) SULFATE [J].
BARNETT, CJ ;
CULLINAN, GJ ;
GERZON, K ;
HOYING, RC ;
JONES, WE ;
NEWLON, WM ;
POORE, GA ;
ROBISON, RL ;
SWEENEY, MJ ;
TODD, GC ;
DYKE, RW ;
NELSON, RL .
JOURNAL OF MEDICINAL CHEMISTRY, 1978, 21 (01) :88-96
[3]
INDUCTION OF REVERSIBLE PROTEIN-LINKED DNA BREAKS IN HUMAN OSTEOGENIC-SARCOMA CELLS BY NOVEL CYTOCIDAL COLCHICINE DERIVATIVES WHICH INHIBIT DNA TOPOISOMERASE-II INVITRO - ABSENCE OF CROSS-RESISTANCE IN A COLCHICINE-RESISTANT SUB-CLONE [J].
BASTOW, KF ;
TATEMATSU, H ;
BORI, ID ;
FUKUSHIMA, Y ;
SUN, L ;
GOZ, B ;
LEE, KH .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1993, 3 (06) :1045-1050
[4]
INHIBITION OF DNA TOPOISOMERASES BY SANGUIIN H-6, A CYTOTOXIC DIMERIC ELLAGITANNIN FROM SANGUISORBA-OFFICINALIS [J].
BASTOW, KF ;
BORI, ID ;
FUKUSHIMA, Y ;
KASHIWADA, Y ;
TANAKA, T ;
NONAKA, G ;
NISHIOKA, I ;
LEE, KH .
PLANTA MEDICA, 1993, 59 (03) :240-245
[5]
Antitumor agents .173. Synthesis and evaluation of camptothecin-4 beta-amino-4'-O-demethyl epipodophyllotoxin conjugates as inhibitors of mammalian DNA topoisomerases and as cytotoxic agents [J].
Bastow, KF ;
Wang, HK ;
Cheng, YC ;
Lee, KH .
BIOORGANIC & MEDICINAL CHEMISTRY, 1997, 5 (08) :1481-1488
[6]
BROSSI A, 1984, ALKALOIDS, pCH23
[7]
CHANG JY, 1991, CANCER RES, V51, P1755
[8]
ANTI-TUMOR AGENTS .50. MORINDAPARVIN-A, A NEW ANTILEUKEMIC ANTHRAQUINONE, AND ALIZARIN-1-METHYL ETHER FROM MORINDA-PARVIFOLIA, AND THE ANTILEUKEMIC ACTIVITY OF THE RELATED DERIVATIVES [J].
CHANG, P ;
LEE, KH ;
SHINGU, T ;
HIRAYAMA, T ;
HALL, IH ;
HUANG, HC .
JOURNAL OF NATURAL PRODUCTS, 1982, 45 (02) :206-210
[9]
ANTITUMOR AGENTS .75. SYNTHESIS OF CYTOTOXIC ANTHRAQUINONES DIGIFERRUGINOL AND MORINDAPARVIN-B [J].
CHANG, P ;
LEE, KH .
JOURNAL OF NATURAL PRODUCTS, 1985, 48 (06) :948-951
[10]
ANTITUMOR AGENTS .67. CYTO-TOXIC ANTILEUKEMIC ANTHRAQUINONES FROM MORINDA-PARVIFOLIA [J].
CHANG, P ;
LEE, KH .
PHYTOCHEMISTRY, 1984, 23 (08) :1733-1736