学术探索
学术期刊
新闻热点
数据分析
智能评审

Synthesis and biological evaluation of N-heterocyclic indolyl glyoxylamides as orally active anticancer agents

被引：166
作者：
Li, WT
Hwang, DR
Chen, CP
Shen, CW
Huang, CL
Chen, TW
Lin, CH
Chang, YL
Chang, YY
Lo, YK
Tseng, HY
Lin, CC
Song, JS
Chen, HC
Chen, SJ
Wu, SH
Chen, CT
机构：
[1] Natl Hlth Res Inst, Div Biotechnol & Pharmaceut Res, Taipei 114, Taiwan
[2] Natl Yang Ming Univ, Inst Microbiol & Immunol, Taipei 112, Taiwan
来源：
JOURNAL OF MEDICINAL CHEMISTRY | 2003年 / 46卷 / 09期
关键词：
D O I：
10.1021/jm020471r
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A series of N-heterocyclic indolyl glyoxylamides were synthesized and evaluated for in vitro and in vivo anticancer activities. They exhibited a broad spectrum of anticancer activity not only in murine leukemic cancer cells but also in human gastric, breast, and uterus cancer cells as well as their multidrug resistant sublines with a wide range of IC50 values. They also induced apoptosis and caused DNA fragmentation in human gastric cancer cells. Among the compounds studied, 7 showed the most potent activity of growth inhibition (IC50 = 17-1711 nM) in several human cancer cells. Given orally, compounds 7 and 13 dose-dependently prolonged the survival of animals inoculated with P388 leukemic cancer cells. N-Heterocyclic indolyl glyoxylamides may be useful as orally active chemotherapeutic agents against cancer and refractory cancerous diseases of multidrug resistance phenotype.
引用
收藏
页码：1706 / 1715
页数：10
相关论文
共 33 条
[1]   New small-molecule tubulin inhibitors [J].
Bacher, G ;
Beckers, T ;
Emig, P ;
Klenner, T ;
Kutscher, B ;
Nickel, B .
PURE AND APPLIED CHEMISTRY, 2001, 73 (09) :1459-1464
[2]  
Bacher G, 2001, CANCER RES, V61, P392
[3]   ACYLATION OF THE ZINC SALT OF INDOLE [J].
BERGMAN, J ;
VENEMALM, L .
TETRAHEDRON, 1990, 46 (17) :6061-6066
[4]  
Berry J. M., 1997, J CHEM SOC P1, V8, P1147
[5]  
Chaudhari SS, 1999, SYNLETT, P1763
[6]   Orally-effective, long-acting sorbitol dehydrogenase inhibitors: Synthesis, structure-activity relationships, and in vivo evaluations of novel heterocycle-substituted piperazino-pyrimidines [J].
Chu-Moyer, MY ;
Ballinger, WE ;
Beebe, DA ;
Berger, R ;
Coutcher, JB ;
Day, WW ;
Li, JC ;
Mylari, BL ;
Oates, PJ ;
Weekly, RM .
JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (02) :511-528
[7]   Norepinephrine stimulates apoptosis in adult rat ventricular myocytes by activation of the β-adrenergic pathway [J].
Communal, C ;
Singh, K ;
Pimentel, DR ;
Colucci, WS .
CIRCULATION, 1998, 98 (13) :1329-1334
[8]   Prediction of hydrophobic (lipophilic) properties of small organic molecules using fragmental methods: An analysis of ALOGP and CLOGP methods [J].
Ghose, AK ;
Viswanadhan, VN ;
Wendoloski, JJ .
JOURNAL OF PHYSICAL CHEMISTRY A, 1998, 102 (21) :3762-3772
[9]   MICROCULTURE TETRAZOLIUM ASSAYS - A COMPARISON BETWEEN 2 NEW TETRAZOLIUM SALTS, XTT AND MTS [J].
GOODWIN, CJ ;
HOLT, SJ ;
DOWNES, S ;
MARSHALL, NJ .
JOURNAL OF IMMUNOLOGICAL METHODS, 1995, 179 (01) :95-103
[10]   4-hydroxy-5,6-dihydropyrones as inhibitors of HIV protease: The effect of heterocyclic substituents at C-6 on antiviral potency and pharmacokinetic parameters [J].
Hagen, SE ;
Domagala, J ;
Gajda, C ;
Lovdahl, M ;
Tait, BD ;
Wise, E ;
Holler, T ;
Hupe, D ;
Nouhan, C ;
Urumov, A ;
Zeikus, G ;
Zeikus, E ;
Lunney, EA ;
Pavlovsky, A ;
Gracheck, SJ ;
Saunders, J ;
VanderRoest, S ;
Brodfuehrer, J .
JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (14) :2319-2332
1234