Total Synthesis and Anti-inflammatory Activity of Asperjinone and Asperimide C

Total syntheses of two γ-butenolide natural products, asperjinone (1) and asperimide C (2) in both racemic and chiral forms have been accomplished utilizing Basavaiah’s one-pot Friedel–Crafts/maleic anhydride formation protocol as a key strategy. Our syntheses verified the revised structure of 1 pro...

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Published in:	Journal of natural products (Washington, D.C.) Vol. 87; no. 8; pp. 2045 - 2054
Main Authors:	Thongpat, Kittisak, Milehman, Natthawat, Rojanaverawong, Worarat, Holasut, Pannita, Soodvilai, Sunhapas, Vaddhanaphuti, Chutima S., Tadpetch, Kwanruthai
Format:	Journal Article
Language:	English
Published:	United States American Chemical Society and American Society of Pharmacognosy 23-08-2024
Subjects:	4-Butyrolactone - analogs & derivatives Animals Anti-Inflammatory Agents - chemical synthesis Anti-Inflammatory Agents - chemistry Anti-Inflammatory Agents - pharmacology Biological Products - chemical synthesis Biological Products - chemistry Biological Products - pharmacology Cyclooxygenase 2 - metabolism Inflammation - chemically induced Inflammation - drug therapy Interleukin-1beta - metabolism Interleukin-6 - metabolism Lipopolysaccharides - pharmacology Molecular Structure Nitric Oxide - antagonists & inhibitors Nitric Oxide - biosynthesis Nitric Oxide Synthase Type II - metabolism Tumor Necrosis Factor-alpha - metabolism
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Summary:	Total syntheses of two γ-butenolide natural products, asperjinone (1) and asperimide C (2) in both racemic and chiral forms have been accomplished utilizing Basavaiah’s one-pot Friedel–Crafts/maleic anhydride formation protocol as a key strategy. Our syntheses verified the revised structure of 1 proposed by Williams et al. and the structure and absolute configuration of 2 reported by the Li group. This work also discloses the unprecedented anti-inflammatory activity of 1. Synthetic 1 exhibited significant anti-inflammatory activity in renal proximal tubular epithelial cells (RPTEC) by suppression of gene expression of pro-inflammatory cytokines TNF-α, IL-1β and IL-6 under LPS-induced renal inflammation condition and was superior to (S)-1, rac-2, 2, and a positive drug control, indomethacin. Moreover, compound 1 inhibited downstream signaling of inflammation by significantly reducing iNOS and COX-2 gene expression and total NO production. The anti-inflammatory activity of asperjinone (1) renders it a potential and promising candidate for developing novel anti-inflammatory agents against inflammation worsening acute kidney injury.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0163-3864 1520-6025 1520-6025
DOI:	10.1021/acs.jnatprod.4c00557