The known indole-3-acetyl anthranilate lindolin A from the early-diverging fungus Linderina pennispora , along with three novel semisynthetic congeners, were identified as selective inhibitors of prostaglandin E 2 (PGE 2 ) formation. Lindolins specifically suppress the expression of the microsomal prostaglandin E 2 synthase-1 (mPGES-1) gene in M1-polarized human macrophages, resulting in markedly reduced mPGES-1 protein levels and a consequent decrease in PGE 2 production, while leaving other lipid mediators largely unaffected. The biosynthesis of lindolins involves the promiscuous N -acyltransferase LinB, which accepts a variety of substituted anthranilic acids as acceptor substrates, thereby enabling the in vitro generation of an analog library. Structure–activity relationship studies revealed that four lindolin analogs with enhanced anti-inflammatory activity possess an ortho -substituted carboxyl group, a structural feature shared with the clinically used antiallergic drug tranilast. Due to their high selectivity toward the mPGES-1 gene expression, lindolins represent promising lead structures for the development of selective mPGES-1 inhibitors with a novel mode of action. Moreover, these findings highlight early-diverging fungi as underestimated source of compounds with pharmaceutical potential. This publication is licensed under You are free to share (copy and redistribute) this article in any medium or format and to adapt (remix, transform, and build upon) the material for any purpose, even commercially within the parameters below: Creative Commons (CC): This is a Creative Commons license. Attribution (BY): Credit must be given to the creator. *Disclaimer This summary highlights only some of the key features and terms of the actual license. It is not a license and has no legal value. Carefully review the actual license before using these materials. You are free to share (copy and redistribute) this article in any medium or format and to adapt (remix, transform, and build upon) the material for any purpose, even commercially within the parameters below: Creative Commons (CC): This is a Creative Commons license. Attribution (BY): Credit must be given to the creator. *Disclaimer This summary highlights only some of the key features and terms of the actual license. It is not a license and has no legal value. Carefully review the actual license before using these materials. You are free to share (copy and redistribute) this article in any medium or format and to adapt (remix, transform, and build upon) the material for any purpose, even commercially within the parameters below: Creative Commons (CC): This is a Creative Commons license. Attribution (BY): Credit must be given to the creator. *Disclaimer This summary highlights only some of the key features and terms of the actual license. It is not a license and has no legal value. Carefully review the actual license before using these materials.
Jordan et al. (Wed,) studied this question.
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