Inhibition of Monoamine Oxidase by Anithiactins from Streptomyces sp.

Abstract

Monoamine oxidase (MAO) is found in most cell types and catalyzes the oxidation of monoamines. Three anithiactins (A-C, modified 2-phenylthiazoles) isolated from Streptomyces sp. were tested for inhibitory activity of two isoforms, MAO-A and MAO-B. Anithiactin A was effective and selective for the inhibition of MAO-A, with an IC50 value of 13.0 µM; however, it was not effective for the inhibition of MAO-B. Anithiactins B and C were weaker inhibitors for MAO-A and MAO-B. Anithiactin A was a reversible and competitive inhibitor for MAO-A with a Ki value of 1.84 µM. The hydrophobic methyl substituent in anithiactin A may play an important role in the inhibition of MAO-A. It is suggested that anithiactin A is a selective reversible inhibitor for MAO-A, with moderate potency, and can be considered a new potential lead compound for further development of novel reversible inhibitors for MAO-A.

Marine natural products with monoamine oxidase (MAO) inhibitory activity

“…Microbial sources were also extensively studied, such as in the case of pimprinine, transcinnamic acid amid and phenethylamine (Takeuchi et al 1973). However, there are only four papers reporting on marine MAOIs which have been published since 1973 (Lee et al 1999;Lee et al 2015;Lee, Choi, et al 2017;, and these are mostly focussed on Streptomycetes as a source.…”

Potent Inhibition of Monoamine Oxidase B by a Piloquinone from Marine-Derived Streptomyces sp. CNQ-027

“…Keywords: Monoamine oxidase, piloquinone, Streptomyces sp. CNQ-027, potent selective inhibitor, competitive inhibitor limited information about MAO inhibitors has been reported from microbial metabolites [14][15][16]. To explore and extend the screening of MAO inhibitors, we selected bacterial and fungal metabolites as attractive sources for investigation, especially marine microorganisms.…”

“…Marine actinomycetes have been investigated as drug-discovery sources [17]. Recently, MAO-A selective inhibitory activity was reported by a compound anithiactin from a Streptomyces sp., isolated from tidal flats or deep-sea sediments [15].…”

“…Clorgyline and pargyline were from a monoamine oxidase kit supplied by BioAssay Systems (USA). The initial rates of oxidation were measured in a 1 ml cuvette containing 50 mM of sodium phosphate (pH 7.4) at 25ºC, as described previously, except for the substrate concentrations and assay times [15,16]. In this study, the activity of MAO-A was assayed with 0.06 mM of kynuramine as the substrate at 316 nm for 20 min, whereas that of MAO-B was assayed with 0.6 mM of benzylamine at 250 nm for 30 min.…”

“…Anithiactin A from the Streptomyces sp. effectively inhibited recombinant human MAO-A (IC 5 0 μM)[15]. Alternariol monomethyl ether from a fungus, Alternaria brassicae, potently inhibited recombinant human MAO-A (IC 5 71 μM)[16].…”