Discovery of p-Terphenyl Metabolites as Potential Phosphodiesterase PDE4D Inhibitors from the Coral-Associated Fungus Aspergillus sp. ITBBc1
文献类型： 外文期刊
作者： Guo, Zhikai 1 ; Abulaizi, Ailiman 6 ; Huang, Ling 5 ; Xiong, Zijun 1 ; Zhang, Shiqing 1 ; Liu, Tianmi 4 ; Wang, Rong 3 ;
作者机构： 1.Chinese Acad Trop Agr Sci, Hainan Key Lab Trop Microbe Resources, Inst Trop Biosci & Biotechnol, Haikou 571101, Peoples R China
2.Hainan Inst Trop Agr Resources, Key Lab Biol & Genet Resources Trop Crops Hainan, Haikou 571101, Peoples R China
3.Hainan Acad Ocean & Fisheries Sci, Hainan Prov Key Lab Trop Maricultural Technol, Haikou 571126, Peoples R China
4.Hainan Aquat Technol Extens Stn, Hainan Testing Ctr Qual & Safety Aquat Prod, Haikou 570206, Peoples R China
5.Hainan Univ, Key Lab Trop Biol Resources, Minist Educ, Sch Pharmaceut Sci, Haikou 570208, Peoples R China
6.Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Inst Funct Biomol, Sch Life Sci, Nanjing 210023, Peoples R China
关键词： coral-associated fungus; Aspergillus sp; natural products; p-terphenyls; phosphodiesterase PDE4D inhibitor
期刊名称：MARINE DRUGS （ 影响因子：6.085； 五年影响因子：6.044 ）
ISSN：
年卷期： 2022 年 20 卷 11 期
页码：
收录情况： SCI
摘要： Chemical investigation of the fermentation extract of the coral-associated fungus Aspergillus sp. ITBBc1 led to the discovery of five unreported p-terphenyl derivatives, sanshamycins A-E (1-5), together with five previously described analogues, terphenyllin (6), 3-hydroxyterphenyllin (7), candidusin A (8), 4,5-dimethoxycandidusin A (9), and candidusin C (10). Their structures were elucidated by HRESIMS data and NMR spectroscopic analysis. Compound 1 represents the first example of p-terphenyls with an aldehyde substitution on the benzene ring. Compounds 2-4 feature varying methoxyl and isopentenyl substitutions, while compound 5 features a five-membered lactone linked to a biphenyl. These findings expand the chemical diversity of the family of p-terphenyl natural products. Compounds 1-6 and 9 were evaluated for their inhibitory activity against type 4 phosphodiesterase (PDE4), which is a fascinating drug target for treatment of inflammatory, respiratory, and neurological diseases. Compound 3 was the most potent and exhibited PDE4D inhibitory activity with an IC50 value of 5.543 mu M.
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