Synthesis and biological evaluation of novel 5-hydroxylaminoisoxazole derivatives as lipoxygenase inhibitors and metabolism enhancing agents. Issue 4 (15th February 2016)

• Record Type: Journal Article
• Authors: Averina, Elena B.; Vasilenko, Dmitry A.; Gracheva, Yulia A.; Grishin, Yuri K.; Radchenko, Eugene V.; Burmistrov, Vladimir V.; Butov, Gennady M.; Neganova, Margarita E.; Serkova, Tatyana P.; Redkozubova, Olga M.; Shevtsova, Elena F.; Milaeva, Elena R.; Kuznetsova, Tamara S.; Zefirov, Nikolay S.
• Is Part Of: Bioorganic & medicinal chemistry. Volume 24:Issue 4(2016)
• Page Start: 712
• Page End: 720
• Publication Date: 2016-02-15
• Subjects: Isoxazole -- Heterocyclization -- Reduction -- Lipoxygenase -- Mitochondria; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2015.12.040
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: A versatile synthesis of novel 5-hydroxylaminoisoxazoles bearing adamantane moieties has been accomplished using the heterocyclization reactions of readily available unsaturated esters by the treatment with tetranitromethane in the presence of triethylamine and subsequent reduction of resulting 5-nitroisoxazoles by SnCl2 with the participation of THF. A number of obtained isoxazole derivatives were evaluated for their antioxidative activity, inhibition of lipoxygenases and impact on the rat liver mitochondria. The majority of tested compounds demonstrated moderate antiradical activity in DPPH test (up to EC50 16 μM). The same compounds strongly inhibited soybean lipoxygenase (up to IC50 0.4 μM) and Fe 2+ - and Fe 3+ -induced lipid peroxidation (LP) of rat brain cortex homogenate (up to IC50 0.3 μM). All tested isoxazole derivatives promoted the phosphorylating respiratory activity simultaneously with maximal stimulated respiratory activity of mitochondria and do not reveal any toxicity towards the primary culture of rat cortex neurons.