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Bioorg Med Chem. 2012 Dec 15;20(24):7040-50. doi: 10.1016/j.bmc.2012.10.005. Epub 2012 Oct 16.

Inhibition of monoamine oxidase by 8-[(phenylethyl)sulfanyl]caffeine analogues.

Author information

1
Pharmaceutical Chemistry, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa.

Abstract

In a previous study we have investigated the monoamine oxidase (MAO) inhibitory properties of a series of 8-sulfanylcaffeine analogues. Among the compounds studied, 8-[(phenylethyl)sulfanyl]caffeine (IC(50) = 0.223 μM) was found to be a particularly potent inhibitor of the type B MAO isoform. In an attempt to discover potent MAO inhibitors and to further examine the structure-activity relationships (SAR) of MAO inhibition by 8-sulfanylcaffeine analogues, in the present study a series of 8-[(phenylethyl)sulfanyl]caffeine analogues were synthesized and evaluated as inhibitors of human MAO-A and -B. The results document that substitution on C3 and C4 of the phenyl ring with alkyl groups and halogens yields 8-[(phenylethyl)sulfanyl]caffeine analogues which are potent and selective MAO-B inhibitors with IC(50) values ranging from 0.017 to 0.125 μM. The MAO inhibitory properties of a series of 8-sulfinylcaffeine analogues were also examined. The results show that, compared to the corresponding 8-sulfanylcaffeine analogues, the 8-sulfinylcaffeins are weaker MAO-B inhibitors. Both the 8-sulfanylcaffeine and 8-sulfinylcaffeine analogues were found to be weak MAO-A inhibitors. This study also reports the MAO inhibition properties of selected 8-[(phenylpropyl)sulfanyl]caffeine analogues.

PMID:
23122934
DOI:
10.1016/j.bmc.2012.10.005
[Indexed for MEDLINE]

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