In:
Letters in Drug Design & Discovery, Bentham Science Publishers Ltd., Vol. 16, No. 10 ( 2019-09-19), p. 1157-1166
Abstract:
A new series of O-benzyloximes derived from eugenol was synthesized
and was evaluated for its antinociceptive and anti-inflammatory properties. Methods: : The target compounds were obtained in good global 25-28% yields over 6 steps, which
led us to identify compounds (Z)-5,6-dimethoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-one-O-(4- (methylthio)benzyloxime (8b), (Z)-5,6-dimethoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-one-O-4-
bromobenzyloxime (8d) and (Z)-5,6-dimethoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-one-O-4- (methylsulfonyl)benzyloxime (8f) as promising bioactive prototypes. Results:: These compounds have significant analgesic and anti-inflammatory effects, as evidenced
by formalin-induced mice paw edema and carrageenan-induced mice paw edema tests. In the formalin test, compounds 8b and 8f evidenced both anti-inflammatory and direct analgesic activities
and in the carrageenan-induced paw edema, with compounds 8c, 8d, and 8f showing the best inhibitory effects, exceeding the standard drugs indomethacin and celecoxib. Conclusion: : Molecular docking studies have provided additional evidence that the pharmacological
profile of these compounds may be related to inhibition of COX enzymes, with slight preference for COX-1. These results led us to identify the new O-benzyloxime ethers 8b, 8d and 8f as orally bioactive
prototypes, with a novel structural pattern capable of being explored in further studies aiming at their optimization and development as drug candidates.
Type of Medium:
Online Resource
ISSN:
1570-1808
DOI:
10.2174/1570180815666180620145609
Language:
English
Publisher:
Bentham Science Publishers Ltd.
Publication Date:
2019
SSG:
15,3
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