Synthesis of a Novel Siliconized Analog of Clofibrate (Silafibrate) and Comparison of their Anti-inflammatory Activities

Author(s):

Mojtaba Ziaee , Morteza Samini , Mohammad Bolourtchian , Mohammad Ghaffarzadeh , Maryam Ahmadi , Mohammad Ali Eghbal , Arash Khorrami , Sina Andalib , Nasrin Maleki-Dizaji , Alireza Garjani

Message:
Abstract:
Fibrates, as hypolipidemic drugs known as agonists of peroxisome proliferator-activated receptors, diminish inflammatory responses. Studies have shown that incorporation of a silicon atom into a drug structure improves its pharmacological potency, modifies its selectivity toward a given target, or changes its metabolic rate, in addition to increasing the lipophilicity of the compounds. A siliconized analog of clofibrate, ethyl-2-methyl-2-(4-(trimethylsilyl)phenoxy)propionate was synthesized, whereby the chlorine atom in the phenoxy ring was replaced by a trimethylsilyl group. The anti-inflammatory effects of the siliconized analog (silafibrate) were evaluated in an air-pouch model of inflammation and compared with those of clofibrate. Oral administration of both drugs produced a significant anti-inflammatory action by reducing carrageenan induced pouch leukocyte recruitment, exudates production, and granulated tissue weight. The silicon isostere of clofibrate has improved anti-inflammatory properties.
Language:
English
Published:
Iranian Journal of Pharmaceutical Research, Volume:11 Issue: 1, Winter 2012
Page:
91
https://magiran.com/p969123