Structure - Cytotoxicity relationships of some helenanolide-type sesquiterpene lactones

被引:113
作者
Beekman, AC
Woerdenbag, HJ
vanUden, W
Pras, N
Konings, AWT
Wikstrom, HV
Schmidt, TJ
机构
[1] UNIV GRONINGEN,GRONINGEN INST DRUG STUDIES,CTR PHARM,DEPT PHARMACEUT BIOL,NL-9713 AV GRONINGEN,NETHERLANDS
[2] UNIV GRONINGEN,GRONINGEN INST DRUG STUDIES,CTR PHARM,DEPT MED CHEM,NL-9713 AV GRONINGEN,NETHERLANDS
[3] UNIV GRONINGEN,GRONINGEN INST DRUG STUDIES,DEPT RADIOBIOL,NL-9713 BZ GRONINGEN,NETHERLANDS
[4] UNIV DUSSELDORF,INST PHARMAZEUT BIOL,D-40225 DUSSELDORF,GERMANY
来源
JOURNAL OF NATURAL PRODUCTS | 1997年 / 60卷 / 03期
关键词
D O I
10.1021/np960517h
中图分类号
Q94 [植物学];
学科分类号
071001 ;
摘要
This study deals with the cytotoxicity of helenanolide-type (10 alpha-methylpseudoguaianolide) sesquiterpene lactones. We determined the influence of substitution patterns on the toxicity of 21 helenanolides to a cloned Ehrlich ascites tumor cell line, EN2. Within a series of helenalin esters, the acetate (2) and isobutyrate (3) were more toxic than helenalin itself (1). Esters with larger acyl groups (tiglate 4 and isovalerate 5) exhibited a decreased toxicity compared with the parent alcohol (1). Similar relationships were observed between the 6,8-diastereomer of helenalin, mexicanin I (6) and its acetate (7) and isovalerate (8). In contrast, cytotoxicity within a series of 11 alpha,13-dihydrohelenalin esters (9-12) was shown to be directly related to the size and lipophilicity of the ester side chain, dihydrohelenalin (9) being the least toxic compound in this group. Investigation of several 2,3-dihydrohelenalin derivatives (13-21) with 2 alpha-hydroxy-4-oxo- and 2 alpha,4 alpha-dihydroxy- or -O-acyl-substituted cyclopentane rings (arnifolins and chamissonolides, respectively), for which no pharmacological data have been reported so far, revealed further interesting influences of the substitution pattern on cytotoxicity. The results may be interpreted in terms of lipophilicity and steric effects on the accessibility of the reactive sites considered responsible for biological activity.
引用
收藏
页码:252 / 257
页数:6
相关论文
共 25 条
[1]  
Beekman AC, 1996, PHYTOTHER RES, V10, P140, DOI 10.1002/(SICI)1099-1573(199603)10:2&lt
[2]  
140::AID-PTR792&gt
[3]  
3.0.CO
[4]  
2-D
[5]  
CARMICHAEL J, 1987, CANCER RES, V47, P936
[6]  
Grippo A A, 1992, Drug Des Discov, V8, P191
[7]   ANTITUMOR AGENTS .21. PROPOSED MECHANISM FOR INHIBITION OF CANCER GROWTH BY TENULIN AND HELENALIN AND RELATED CYCLOPENTENONES [J].
HALL, IH ;
LEE, KH ;
MAR, EC ;
STARNES, CO ;
WADDELL, TG .
JOURNAL OF MEDICINAL CHEMISTRY, 1977, 20 (03) :333-337
[8]   TUMOR INHIBITORS .69. STRUCTURE-CYTOTOXICITY RELATIONSHIPS AMONG SESQUITERPENE LACTONES [J].
KUPCHAN, SM ;
EAKIN, MA ;
THOMAS, AM .
JOURNAL OF MEDICINAL CHEMISTRY, 1971, 14 (12) :1147-&
[9]   REACTIONS OF ALPHA METHYLENE LACTONE TUMOR INHIBITORS WITH MODEL BIOLOGICAL NUCLEOPHILES [J].
KUPCHAN, SM ;
FESSLER, DC ;
EAKIN, MA ;
GIACOBBE, TJ .
SCIENCE, 1970, 168 (3929) :376-&
[10]  
KUPCHAN SM, 1974, FED PROC, V33, P2288