Anti-Inflammatory Secondary Metabolites from <i>Penicillium</i> sp. NX-S-6

Anti-Inflammatory Secondary Metabolites from <i>Penicillium</i> sp. NX-S-6

Five new natural products, including two sorbicillinoids (<b>1</b>–<b>2</b>), one indolinone alkaloid (<b>10</b>), one tetracyclic steroid (<b>11</b>), and one α-pyrone derivative (<b>14</b>), were identified from the endophytic <i>Pe...

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Bibliographic Details
Main Authors: Hanyang Peng, Jiawen Sun, Rui Zhang, Yuxuan Qiu, Yu Hong, Fengjuan Zhou, Chang Wang, Yang Hu, Xiachang Wang
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Marine Drugs
Subjects:
sorbicillinoid
indolinone alkaloid
steroid
<i>Penicillium</i> sp.
anti-inflammatory
Online Access:https://www.mdpi.com/1660-3397/23/7/280
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Summary:Five new natural products, including two sorbicillinoids (<b>1</b>–<b>2</b>), one indolinone alkaloid (<b>10</b>), one tetracyclic steroid (<b>11</b>), and one α-pyrone derivative (<b>14</b>), were identified from the endophytic <i>Penicillium</i> sp. NX-S-6, together with thirteen known natural products. The structures of new compounds were unambiguously elucidated by comprehensive spectroscopic analyses (NMR, MS), as well as electronic circular dichroism (ECD) calculation. Notably, quinosorbicillinol (<b>1</b>) was identified as a rare hybrid sorbicillinoid incorporating a quinolone moiety, representing a unique structural scaffold in this natural product class. Biological evaluation revealed that Compounds <b>1</b>, <b>4</b> and <b>8</b> potently inhibited the production of nitric oxide and interleukin 6 in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Mechanistic studies furthermore demonstrated that Compounds <b>4</b> and <b>8</b> effectively suppressed interleukin-1β secretion in LPS-induced immortalized mouse bone marrow-derived macrophages (iBMDMs) by blocking NLRP3 inflammasome activation. This inhibition was attributed to their ability to disrupt the assembly of the NLRP3-caspase-1 complex, a key event in the pathogenesis of inflammatory disorders. These findings not only expand the structural diversity of endophyte-derived natural products but also highlight their potential as lead compounds for developing anti-inflammatory therapeutics targeting the NLRP3 pathway.
ISSN:1660-3397

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