Design, synthesis and biological evaluation of novel hydrogen sulfide releasing capsaicin derivatives

A series of new hybrids of capsaicin or dihydrocapsaicin bearing various H2S-releasing moieties were prepared and evaluated in an effort to improve the activity of CAP and alleviate its irritating effects. [Display omitted] Capsaicin (CAP), the prototypical TRPV1 agonist, is the major active compone...

Full description

Saved in:
Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2018-05, Vol.26 (9), p.2632-2639
Main Authors: Gao, Mingxiang, Li, Jinyu, Nie, Cunbin, Song, Beibei, Yan, Lin, Qian, Hai
Format: Article
Language:English
Subjects:
Analgesic
Analgesics - chemical synthesis
Analgesics - chemistry
Analgesics - pharmacology
Animals
Anticancer
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Capsaicin
Capsaicin - analogs & derivatives
Capsaicin - chemical synthesis
Capsaicin - pharmacology
Cell Line, Tumor
Doxorubicin - pharmacology
Drug Design
Gastric Mucosa - drug effects
Gastric mucosa irritation
HEK293 Cells
Humans
Hydrogen sulfide
Hydrogen Sulfide - metabolism
Male
Mice
Rats
Structure-Activity Relationship
TRPV Cation Channels - agonists
TRPV1 agonist
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:A series of new hybrids of capsaicin or dihydrocapsaicin bearing various H2S-releasing moieties were prepared and evaluated in an effort to improve the activity of CAP and alleviate its irritating effects. [Display omitted] Capsaicin (CAP), the prototypical TRPV1 agonist, is the major active component in chili peppers with health-promoting benefits. However, its use is limited by the low bioavailability and irritating quality. In this study, for improving the activity of CAP and alleviating its irritating effects, a series of H2S-releasing CAPs were designed and synthesized by combining capsaicin and dihydro capsaicin with various hydrogen sulfide donors. The resulting compounds were evaluated their TRPV1 agonist activity, analgesic activity, anticancer activities, H2S-releasing ability, and gastric mucosa irritation. Biological evaluation indicated that the most active compound B9, containing 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione moiety as H2S donor, had better analgesic activity and displayed more potent cytotoxic effects on the test cell lines than the lead compound CAP. Furthermore, the preferred compound, B9 reduced rat gastric mucosa irritation caused by CAP. Notably, the improved properties of this derivative are associated with its H2S-releasing capability.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2018.04.031