Myxochelin- and Pseudochelin-Derived Lipoxygenase Inhibitors from a Genetically Engineered Strain.

J Nat Prod

Chair of Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy , Friedrich-Schiller-University, Philosophenweg 14 , 07743 Jena , Germany.

Published: September 2019

Precursor-directed biosynthesis was used to introduce selected aryl carboxylic acids into the pseudochelin pathway, which had recently been assembled in . Overall, 14 previously undescribed analogues of the natural products myxochelin B and pseudochelin A were generated and structurally characterized. A subset of 10 derivatives together with their parental molecules were evaluated for their activity toward human 5-lipoxygenase. This testing revealed pseudochelin A as the most potent 5-lipoxygenase inhibitor among the naturally occurring compounds, whereas myxochelin A is the least active. Replacement of the catechol moieties in myxochelin B and pseudochelin A affected the bioactivity to different degrees.

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http://dx.doi.org/10.1021/acs.jnatprod.9b00403DOI Listing

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