Antinociceptive activities of α-truxillic acid and β-truxinic acid derivatives

被引:34
作者
Chi, YM
Nakamura, M
Zhao, XY
Yoshizawa, T
Yan, WM
Hashimoto, F
Kinjo, J
Nohara, T
Sakurada, S
机构
[1] Seiwa Pharmaceut Ltd, Ibaraki 3191535, Japan
[2] Beijing Univ Tradit Chinese Med & Pharm, Beijing 100029, Peoples R China
[3] Kumamoto Univ, Fac Pharmaceut Sci, Kumamoto 8620973, Japan
[4] Tohoku Pharmaceut Univ, Dept Pharmacol, Aoba Ku, Sendai, Miyagi 9818558, Japan
关键词
alpha-truxillic acid; beta-truxinic acid; anti-inflammatory activity; indomethacin; formalin test;
D O I
10.1248/bpb.29.580
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Our recent study demonstrated that the dimeric structure of alpha-truxillic acid derivatives played an important role in the expression of their anti-inflammatory activities. In the present report, to investigate the correlation between the structure and anti-inflammatory activity, alpha-truxillic acid (1) and its derivatives (2-6), beta-truxinic acid (7) and its derivatives (8-10) were prepared, and their activities were evaluated in the formalin test. All compounds showed only weak or no activities against the neurogenic pain response, but demonstrated significant activities against the inflammatory pain response induced by formalin. The highest anti-inflammatory activities were observed for alpha-truxillic acid (1) and its derivative 4,4'-dihydroxy-alpha-truxillic acid (2). In addition, alpha-truxillic acid (1) and its derivative, alpha-truxillic acid bis(p-nitrophenyl)ester (5), showed higher anti-inflammatory activities than beta-truxinic acid (7) and the corresponding derivative (10). Furthermore, free carboxylic acids (1, 2) showed higher activities than their dimethyl esters (3, 4) and bis(p-nitrophenyl)ester (5). These results confirmed that the m-formation of dimeric structure and the free carboxylic acid were also important for the expression of anti-inflammatory activities. Otherwise, 4,4'-dichloro-beta-truxinic acid (8) had higher activity than its parent compound 7; furthermore, 1,3-dibenzoyl-2,4-di(4-chlorophenyl)cyclobutane (6) also showed strong anti-inflammatory activity. These results suggested that substituents in the phenyl groups were also important for the expression of anti-inflammatory activity. In order to gain information about their activity intensity, the anti-inflammatory activities of 2 and 4,4'-dichlorolated derivatives (6, 8) were compared with that of indomethacin (a nonsteroidal anti-inflammatory drug) in the formalin test. As a result, compounds 2, 6 and 8 showed stronger anti-inflammatory activities than indomethacin. These results suggested that alpha-truxillic acid and beta-truxinic acid derivatives might be developed into a new type of anti-inflammatory drug.
引用
收藏
页码:580 / 584
页数:5
相关论文
共 16 条
[1]  
BARACCHI A, 1986, HETEROCYCLES, V24, P2863
[2]   Anti-inflammatory activities of α-truxillic acid derivatives and their monomer components [J].
Chi, YM ;
Nakamura, M ;
Yoshizawa, T ;
Zhao, XY ;
Yan, WM ;
Hashimoto, F ;
Kinjo, J ;
Nohara, T ;
Sakurada, S .
BIOLOGICAL & PHARMACEUTICAL BULLETIN, 2005, 28 (09) :1776-1778
[3]   AN ALKALOID FROM INCARVILLEA-SINENSIS [J].
CHI, YM ;
YAN, WM ;
LI, JS .
PHYTOCHEMISTRY, 1990, 29 (07) :2376-2378
[4]   TOPOCHEMISTRY .2. PHOTOCHEMISTRY OF TRANS-CINNAMIC ACIDS [J].
COHEN, MD ;
SCHMIDT, GMJ ;
SONNTAG, FI .
JOURNAL OF THE CHEMICAL SOCIETY, 1964, (JUN) :2000-&
[5]   FORMALIN TEST - QUANTITATIVE STUDY OF ANALGESIC EFFECTS OF MORPHINE, MEPERIDINE, AND BRAIN-STEM STIMULATION IN RATS AND CATS [J].
DUBUISSON, D ;
DENNIS, SG .
PAIN, 1977, 4 (02) :161-174
[6]   THE FORMALIN TEST IN MICE - DISSOCIATION BETWEEN INFLAMMATORY AND NONINFLAMMATORY PAIN [J].
HUNSKAAR, S ;
HOLE, K .
PAIN, 1987, 30 (01) :103-114
[7]   3 PHENOLIC-ACID DERIVATIVES FROM STROMATA OF EPICHLOE-TYPHINA ON PHLEUM-PRATENSE [J].
KOSHINO, H ;
TERADA, SI ;
YOSHIHARA, T ;
SAKAMURA, S ;
SHIMANUKI, T ;
SATO, T ;
TAJIMI, A .
PHYTOCHEMISTRY, 1988, 27 (05) :1333-1338
[8]   TOPOCHEMISTRY .18. SOLID-STATE PHOTOCHEMISTRY OF SOME HETEROCYCLIC ANALOGUES OF TRANS-CINNAMIC ACID [J].
LAHAV, M ;
SCHMIDT, GMJ .
JOURNAL OF THE CHEMICAL SOCIETY B-PHYSICAL ORGANIC, 1967, (03) :239-&
[9]  
LICHTFIELD JT, 1949, J PHARMACOL EXP THER, V96, P99
[10]   STRUCTURE AND CONFORMATION OF CHALCONE PHOTODIMERS AND RELATED COMPOUNDS [J].
MONTAUDO, G ;
CACCAMES.S .
JOURNAL OF ORGANIC CHEMISTRY, 1973, 38 (04) :710-716