N-1, C-3 substituted indoles as 5-LOX inhibitors--in vitro enzyme immunoaasay, mass spectral and molecular docking investigations.

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Singh P, Pooja

N-1, C-3 substituted indoles as 5-LOX inhibitors--in vitro enzyme immunoaasay, mass spectral and molecular docking investigations.

Bioorg Med Chem Lett. 2013 Mar 1;23(5):1433-7. doi: 10.1016/j.bmcl.2012.12.068. Epub 2013 Jan 3.

PubMed ID

23337599 [ View in PubMed

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Abstract

Based upon the structures of some known 5-LOX inhibitors, a set of five compounds carrying appropriate substituents at N-1 and C-3 of indole were synthesized and investigated for 5-LOX inhibitory activities. Fifty percent inhibitory concn (IC(50)) of these compounds ranges from 0.6 to 5 muM and found to be comparable to that of clinically used 5-LOX inhibitor, zileuton. The compounds under present investigations exhibited appreciable interactions with 5-LOX as apparent from their association constants calculated from the mass spectral data. Compound 5a with a tosyl group at N-1 and pyrolidinyl-1,2-dione substituent at C-3 of indole, exhibiting IC(50) 0.6 muM and stoichiometry of 1:7 in the enzyme-compound complex was identified as highly potent 5-LOX inhibitor and seems to be suitable for further investigations.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Zileuton	Arachidonate 5-lipoxygenase	IC 50 (nM)	3700	N/A	N/A	Details