Antimalarial, antiproliferative, and antitumor activities of artemisinin-derived, chemically robust, trioxane dimers

被引:136
作者
Posner, GH [1 ]
Ploypradith, P
Parker, MH
O'Dowd, H
Woo, SH
Northrop, J
Krasavin, M
Dolan, P
Kensler, TW
Xie, SJ
Shapiro, TA
机构
[1] Johns Hopkins Univ, Sch Arts & Sci, Dept Chem, Baltimore, MD 21218 USA
[2] Johns Hopkins Univ, Sch Hyg & Publ Hlth, Div Toxicol Sci, Baltimore, MD 21205 USA
[3] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA
关键词
D O I
10.1021/jm990363d
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Nine C-10 non-acetal derivatives of the natural trioxane artemisinin (1) were prepared as dimers using some novel chemistry. As designed, each dimer was stable chemically. C-10 Olefinic dimers 7 and C-10 saturated dimers 8-13 all showed good to excellent antimalarial and antiproliferative activities in vitro. Dimers 8, 10, and 12 were especially potent and selective at inhibiting growth of some human cancer cell lines in the NCI in vitro 60-cell line assay.
引用
收藏
页码:4275 / 4280
页数:6
相关论文
共 28 条
[21]   Orally active, hydrolytically stable, semisynthetic, antimalarial trioxanes in the artemisinin family [J].
Posner, GH ;
Parker, MH ;
Northrop, J ;
Elias, JS ;
Ploypradith, P ;
Xie, SJ ;
Shapiro, TA .
JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (02) :300-304
[22]   SYNTHESIS AND ANTIMALARIAL ACTIVITIES OF 12-BETA-ALLYLDEOXOARTEMISININ AND ITS DERIVATIVES [J].
PU, YM ;
ZIFFER, H .
JOURNAL OF MEDICINAL CHEMISTRY, 1995, 38 (04) :613-616
[23]  
Reddy BSP, 1999, SYNLETT, P1112
[24]   THE INVERSE ELECTRON-DEMAND DIELS-ALDER REACTION IN POLYMER SYNTHESIS .1. A CONVENIENT SYNTHETIC ROUTE TO DIETHYNYL AROMATIC-COMPOUNDS [J].
ROYLES, BJL ;
SMITH, DM .
JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1994, (04) :355-358
[25]   ANTIMALARIAL ACTIVITY OF NOVEL RING-CONTRACTED ARTEMISININ DERIVATIVES [J].
VENUGOPALAN, B ;
BAPAT, CP ;
KARNIK, PJ ;
CHATTERJEE, DK ;
IYER, N ;
LEPCHA, D .
JOURNAL OF MEDICINAL CHEMISTRY, 1995, 38 (11) :1922-1927
[26]   Copper(I) catalyzed conjugate addition of Grignard reagents to acrylic acids: Homologation of artemisinic acid and subsequent conversion to 9-substituted artemisinin analogs [J].
Vroman, JA ;
Khan, IA ;
Avery, MA .
TETRAHEDRON LETTERS, 1997, 38 (35) :6173-6176
[27]   Direct conversion of pyranose anomeric OH→F→R in the artemisinin family of antimalarial trioxanes [J].
Woo, SH ;
Parker, MH ;
Ploypradith, P ;
Northrop, J ;
Posner, GH .
TETRAHEDRON LETTERS, 1998, 39 (12) :1533-1536
[28]   PT(NH3)2CL2 AND CANCER - OLD COMPOUND WITH A NEW USE [J].
ZIPP, AP ;
ZIPP, SG .
JOURNAL OF CHEMICAL EDUCATION, 1977, 54 (12) :739-741