Structure-activity relationships in a series of melatonin analogues with the low-density lipoprotein oxidation model

被引:52
作者
Gozzo, A
Lesieur, D
Duriez, P
Fruchart, JC
Teissier, E
机构
[1] Univ Lille 2, Inst Chim Pharmaceut, Lille, France
[2] Univ Lille 2, Inst Pasteur, Lille, France
[3] Univ Lille 2, Fac Pharm, Lille, France
关键词
melatonin; low-density lipoprotein; lipid; peroxidation; antioxidant; structure-activity relationship; free radicals;
D O I
10.1016/S0891-5849(99)00020-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Despite an increasing number of publications concerning the antioxidant activity of melatonin, little is known about the structural features responsible for this kind of activity. To understand the role played by the different elements of melatonin structure in its antioxidant activity, we have designed and tested several compounds related to this molecule in the low-density lipoprotein peroxidation model. We present here the results of this study in terms of structure-activity relationships focusing on the influence of the acetamidoethyl side chain, the methoxy group, and the indole heterocycle. In this model, we found that changing the acyl residue generally resulted in more active products. We obtained particularly good results with the nonanoyl derivative which showed a level of activity comparable to that of phenols despite lacking a phenolic function. The presence of a methoxy group in position 5 generally had a beneficial influence on the activity, but when located in position 6, the effects were various. The substitution of a hydroxy for the methoxy group led to phenolic compounds endowed with very high antioxidant activity. Replacing the amide with a ketone function did not affect the activity while replacement with an amine group in some cases resulted in prooxidant compounds. Finally, we compared the efficacy of different aromatic rings. The indole heterocycle proved to be better than benzofurane and naphthalene rings. (C) 1999 Elsevier Science Inc.
引用
收藏
页码:1538 / 1543
页数:6
相关论文
共 32 条
[1]   Antioxidant role of melatonin in lipid peroxidation of human LDL [J].
Abuja, PM ;
Liebmann, P ;
Hayn, M ;
Schauenstein, K ;
Esterbauer, H .
FEBS LETTERS, 1997, 413 (02) :289-293
[2]   MODIFIED FORMS OF LOW-DENSITY-LIPOPROTEIN AND ATHEROSCLEROSIS [J].
AVIRAM, M .
ATHEROSCLEROSIS, 1993, 98 (01) :1-9
[3]   NEW ANTIOXIDANTS INCORPORATING INDOLE AND INDOLINE CHROMOPHORES [J].
BROWN, DW ;
GRAUPNER, PR ;
SAINSBURY, M ;
SHERTZER, HG .
TETRAHEDRON, 1991, 47 (25) :4383-4408
[4]   Characterization of the antioxidant effects of melatonin and related indoleamines in vitro [J].
Chan, TY ;
Tang, PL .
JOURNAL OF PINEAL RESEARCH, 1996, 20 (04) :187-191
[5]   Melatonin, its receptors, and relationships with biological rhythm disorders [J].
Delagrange, P ;
GuardiolaLemaitre, B .
CLINICAL NEUROPHARMACOLOGY, 1997, 20 (06) :482-510
[6]   CONTINUOUS MONITORING OF INVITRO OXIDATION OF HUMAN LOW-DENSITY LIPOPROTEIN [J].
ESTERBAUER, H ;
STRIEGL, G ;
PUHL, H ;
ROTHENEDER, M .
FREE RADICAL RESEARCH COMMUNICATIONS, 1989, 6 (01) :67-75
[7]   COMBINED EFFECTS OF DIAZEPAM AND MELATONIN IN 2 TESTS FOR ANXIOLYTIC ACTIVITY IN THE MOUSE [J].
GUARDIOLALEMAITRE, B ;
LENEGRE, A ;
PORSOLT, RD .
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 1992, 41 (02) :405-408
[8]   DISTRIBUTION AND CHEMICAL COMPOSITION OF ULTRACENTRIFUGALLY SEPARATED LIPOPROTEINS IN HUMAN SERUM [J].
HAVEL, RJ ;
EDER, HA ;
BRAGDON, JH .
JOURNAL OF CLINICAL INVESTIGATION, 1955, 34 (09) :1345-1353
[9]   Melatonin inhibits oxidative modification of human low-density lipoprotein [J].
Kelly, MR ;
Loo, G .
JOURNAL OF PINEAL RESEARCH, 1997, 22 (04) :203-209
[10]   REACTIVITY OF INDOLE-DERIVATIVES TOWARDS OXYGENATED RADICALS [J].
LISSI, EA ;
FAURE, M ;
MONTOYA, N ;
VIDELA, LA .
FREE RADICAL RESEARCH COMMUNICATIONS, 1991, 15 (04) :211-222