title: Synthesis of a Novel Siliconized Analog of Clofibrate (Silafibrate) and Comparison of their Anti-inflammatory Activities.
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.
authors.affiliation: Department of Pharmacology, Science & Research Branch, Islamic Azad University, Tehran, Iran.
authors.forename: Mojtaba
authors.initials: M
authors.lastname: Ziaee
authors.affiliation: Department of Pharmacology, Science & Research Branch, Islamic Azad University, Tehran, Iran.
authors.forename: Morteza
authors.initials: M
authors.lastname: Samini
authors.affiliation: Chemistry and Chemical Engineering Research Center of Iran, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Bolourtchian
authors.affiliation: Chemistry and Chemical Engineering Research Center of Iran, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ghaffarzadeh
authors.affiliation: Chemistry and Chemical Engineering Research Center of Iran, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Ahmadi
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Egbal
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Arash
authors.initials: A
authors.lastname: Khorrami
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Sina
authors.initials: S
authors.lastname: Andalib
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Nasrin
authors.initials: N
authors.lastname: Maleki-Dizaji
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Garjani
keywords: Anti-inflammatory; Clofibrate; Silicon; Siliconized analog