Format

Send to

Choose Destination
Bioorg Med Chem. 2016 Feb 15;24(4):712-20. doi: 10.1016/j.bmc.2015.12.040. Epub 2015 Dec 24.

Synthesis and biological evaluation of novel 5-hydroxylaminoisoxazole derivatives as lipoxygenase inhibitors and metabolism enhancing agents.

Author information

1
Lomonosov Moscow State University, Department of Chemistry, Leninskie Gory, 1-3, Moscow 119991, Russia; IPAC RAS, Severnyi Proezd, 1, Chernogolovka, Moscow Region, 142432, Russia. Electronic address: elaver@org.chem.msu.ru.
2
Lomonosov Moscow State University, Department of Chemistry, Leninskie Gory, 1-3, Moscow 119991, Russia.
3
Lomonosov Moscow State University, Department of Chemistry, Leninskie Gory, 1-3, Moscow 119991, Russia; IPAC RAS, Severnyi Proezd, 1, Chernogolovka, Moscow Region, 142432, Russia.
4
Volgograd State Technical University, VSTU, Lenina Avenue, 28, Volgograd 400005, Russia.
5
IPAC RAS, Severnyi Proezd, 1, Chernogolovka, Moscow Region, 142432, Russia.
6
Lomonosov Moscow State University, Department of Chemistry, Leninskie Gory, 1-3, Moscow 119991, Russia; IPAC RAS, Severnyi Proezd, 1, Chernogolovka, Moscow Region, 142432, Russia. Electronic address: milaeva@med.chem.msu.ru.

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 16μM). The same compounds strongly inhibited soybean lipoxygenase (up to IC50 0.4μM) and Fe(2+)- and Fe(3+)-induced lipid peroxidation (LP) of rat brain cortex homogenate (up to IC50 0.3μM). 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.

KEYWORDS:

Heterocyclization; Isoxazole; Lipoxygenase; Mitochondria; Reduction

PMID:
26753816
DOI:
10.1016/j.bmc.2015.12.040
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center