Journal
RSC ADVANCES
Volume 6, Issue 23, Pages 19271-19279Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c5ra28187c
Keywords
-
Categories
Funding
- DST-WOS-A scheme
Ask authors/readers for more resources
Human 5-lipoxygenase (5-LOX) is an important enzyme in the biosynthesis of leukotrienes and is a target for asthma and allergy treatment. Zileuton is the only drug currently marketed that targets this enzyme (IC50 similar to 1 mu M). So, the development of novel lead compounds is highly desirable. A series of 2-aryl indole, thiazolopyrazole acid, oxadiazolobenzothiophene, 1,4-disubstituted-1,2,3-triazole, 2-amino-4-aryl thiazole and 4,4'-(1,4-phenylene)bis(1,3-thiazole) derivatives when tested against this enzyme resulted in the identification of a potent compound (1d), p-fluoro substituted 2-amino-4-aryl thiazole, with an IC50 of similar to 10 mu M. Another lead compound identified is (4a), a thiazolopyrazole acid derivative (IC50 similar to 40 mu M). All the compounds exhibit poor DPPH radical scavenging activity which suggests that their action occurs not due to the disruption of the redox cycle of iron present in the enzyme (unlike zileuton) but through competitive inhibition, since the V-max remains constant but the K-m increases with an increase in inhibitor concentration. Molecular docking of 1d and 4a to the active site of 5-LOX also supports the experimental data, and suggests that their possible mechanism of action is through competitive inhibition. The current study identifies a promising lead molecule which could be improved further to match the activity of the commercial drug.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available