Structure-activity relationships of the ultrapotent vanilloid resiniferatoxin (RTX): The homovanillyl moiety

被引：13
作者：
Appendino, Giovanni
Ech-Chahad, Abdellah
Minassi, Alberto
Bacchiega, Sara
De Petrocellis, Luciano
Di Marzo, Vincenzo
机构：
[1] Univ Piemonte Orientale, Dipartimento Sci Chim Alimentari Farmaceut & Farm, I-28100 Novara, Italy
[2] CNR, Inst Cibernet Eduardo Cainiello, Endocannabinoid Res Grp, Pozzuoli, NA, Italy
[3] CNR, Inst Biomol Chem, Endocannabinoid Res Grp, Pozzuoli, NA, Italy
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 01期
关键词：
resiniferatoxin (RTX); TRPV1; structure-activity relationships; capsaicin; vanilloids;
D O I：
10.1016/j.bmcl.2006.09.077
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Starting from ROPA (2), analogues of RTX (1a) modified on the acyl side chain were prepared and evaluated for vanilloid activity in HEK-293 cells over-expressing the human recombinant TRPV1. The ROPA motif provided an enhancement of potency sufficient to expand the range of vanillyl surrogates to structural elements (e.g., an unsubstituted phenyl ring) that afford inactive analogues in compounds from the capsaicin series. (c) 2006 Elsevier Ltd. All rights reserved.
引用
收藏
页码：132 / 135
页数：4
相关论文
共 28 条
[1]   STRUCTURE-ACTIVITY RELATIONS OF POLYFUNCTIONAL DITERPENES OF THE DAPHNANE TYPE .1. REVISED STRUCTURE FOR RESINIFERATOXIN AND STRUCTURE-ACTIVITY RELATIONS OF RESINIFERONOL AND SOME OF ITS ESTERS [J].
ADOLF, W ;
SORG, B ;
HERGENHAHN, M ;
HECKER, E .
JOURNAL OF NATURAL PRODUCTS, 1982, 45 (03) :347-354
[2]   Sulfonation with inversion by Mitsunobu reaction: An improvement on the original conditions [J].
Anderson, NG ;
Lust, DA ;
Colapret, KA ;
Simpson, JH ;
Malley, MF ;
Gougoutas, JZ .
JOURNAL OF ORGANIC CHEMISTRY, 1996, 61 (22) :7955-7958
[3]   The taming of capsaicin.: Reversal of the vanilloid activity of N-acylvanillamines by aromatic iodination [J].
Appendino, G ;
Daddario, N ;
Minassi, A ;
Moriello, SM ;
De Petrocellis, L ;
Di Marzo, V .
JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (14) :4663-4669
[4]   Chemoselective esterification of phenolic acids and alcohols [J].
Appendino, G ;
Minassi, A ;
Daddario, N ;
Bianchi, F ;
Tron, GC .
ORGANIC LETTERS, 2002, 4 (22) :3839-3841
[5]  
Appendino G, 2006, PROGR MED CHEM, V44, P145, DOI 10.1016/S0079-6468(05)44404-5
[6]   The capsaicin receptor: a heat-activated ion channel in the pain pathway [J].
Caterina, MJ ;
Schumacher, MA ;
Tominaga, M ;
Rosen, TA ;
Levine, JD ;
Julius, D .
NATURE, 1997, 389 (6653) :816-824
[7]   Resiniferatoxin binds to the capsaicin receptor (TRPV1) near the extracellular side of the S4 transmembrane domain [J].
Chou, MZ ;
Mtui, T ;
Gao, YD ;
Kohler, M ;
Middleton, RE .
BIOCHEMISTRY, 2004, 43 (09) :2501-2511
[8]   TRP channels as cellular sensors [J].
Clapham, DE .
NATURE, 2003, 426 (6966) :517-524
[9]  
Fattorusso E, 2002, EUR J ORG CHEM, V2002, P71, DOI 10.1002/1099-0690(20021)2002:1<71::AID-EJOC71>3.0.CO
[10]  
2-C
123