Discovery of an Indole-Quinazoline Alkaloid as an Anti-kidney Fibrotic Agent from the Marine-Derived SCSIO 41444.
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| Natura: | Artículo científico |
| Lingua: | en |
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Journal of natural products
2026
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| _version_ | 1868266082242920448 |
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| author | She, Jianglian Tian, Lingmin Zhu, Shuru Chen, Yi Gu, Tanwei Zhang, Xi Liu, Yonghong Tang, Lan Zhou, Xuefeng |
| author_facet | She, Jianglian Tian, Lingmin Zhu, Shuru Chen, Yi Gu, Tanwei Zhang, Xi Liu, Yonghong Tang, Lan Zhou, Xuefeng She, Jianglian Tian, Lingmin Zhu, Shuru Chen, Yi Gu, Tanwei Zhang, Xi Liu, Yonghong Tang, Lan Zhou, Xuefeng |
| collection | PubMed - marine biology |
| contents | Discovery of an Indole-Quinazoline Alkaloid as an Anti-kidney Fibrotic Agent from the Marine-Derived SCSIO 41444. She, Jianglian Tian, Lingmin Zhu, Shuru Chen, Yi Gu, Tanwei Zhang, Xi Liu, Yonghong Tang, Lan Zhou, Xuefeng Aspergillus Humans Molecular Structure Alkaloids Animals Indole Alkaloids Marine Biology Quinazolines Fibrosis Kidney Kidney fibrosis represents a hallmark pathological outcome in the progression of chronic kidney diseases. The clinical approval of therapeutics specifically for kidney fibrosis remains lacking to date. Toward the discovery of novel marine-derived drugs leads against kidney fibrosis, a fibronectin (FN)-based assay was used to screen various fractions of the crude extract from the growth medium of sponge-associated fungus SCSIO 41444. A bioassay-guided fractionation process yielded six active compounds (-), including a new indole-quinazoline alkaloid () and an undescribed pyripyropene-type alkaloid (). The structures and absolute configurations of and were determined by analysis of spectroscopic data and electron circular dichroism calculations. Compounds - (10 μM) were all active in the TGF-β1-stimulated HK-2 cell model of kidney fibrosis. The alkaloid demonstrated potent activity, significantly suppressing the protein levels of FN and α-SMA at a concentration as low as 2.5 μM. Based on comprehensive proteomic analysis, was found to decrease thyroid adenoma-associated protein levels, thereby modulating endoplasmic reticulum calcium homeostasis and influencing the progression of kidney fibrosis. These findings suggested that is a promising anti-kidney fibrosis agent with a new mechanism for drug development. |
| format | Artículo científico |
| id | pubmed_41711189 |
| institution | PubMed |
| language | en |
| publishDate | 2026 |
| publisher | Journal of natural products |
| record_format | pubmed |
| spellingShingle | Discovery of an Indole-Quinazoline Alkaloid as an Anti-kidney Fibrotic Agent from the Marine-Derived SCSIO 41444. She, Jianglian Tian, Lingmin Zhu, Shuru Chen, Yi Gu, Tanwei Zhang, Xi Liu, Yonghong Tang, Lan Zhou, Xuefeng Aspergillus Humans Molecular Structure Alkaloids Animals Indole Alkaloids Marine Biology Quinazolines Fibrosis Kidney Discovery of an Indole-Quinazoline Alkaloid as an Anti-kidney Fibrotic Agent from the Marine-Derived SCSIO 41444. She, Jianglian Tian, Lingmin Zhu, Shuru Chen, Yi Gu, Tanwei Zhang, Xi Liu, Yonghong Tang, Lan Zhou, Xuefeng Aspergillus Humans Molecular Structure Alkaloids Animals Indole Alkaloids Marine Biology Quinazolines Fibrosis Kidney Kidney fibrosis represents a hallmark pathological outcome in the progression of chronic kidney diseases. The clinical approval of therapeutics specifically for kidney fibrosis remains lacking to date. Toward the discovery of novel marine-derived drugs leads against kidney fibrosis, a fibronectin (FN)-based assay was used to screen various fractions of the crude extract from the growth medium of sponge-associated fungus SCSIO 41444. A bioassay-guided fractionation process yielded six active compounds (-), including a new indole-quinazoline alkaloid () and an undescribed pyripyropene-type alkaloid (). The structures and absolute configurations of and were determined by analysis of spectroscopic data and electron circular dichroism calculations. Compounds - (10 μM) were all active in the TGF-β1-stimulated HK-2 cell model of kidney fibrosis. The alkaloid demonstrated potent activity, significantly suppressing the protein levels of FN and α-SMA at a concentration as low as 2.5 μM. Based on comprehensive proteomic analysis, was found to decrease thyroid adenoma-associated protein levels, thereby modulating endoplasmic reticulum calcium homeostasis and influencing the progression of kidney fibrosis. These findings suggested that is a promising anti-kidney fibrosis agent with a new mechanism for drug development. |
| title | Discovery of an Indole-Quinazoline Alkaloid as an Anti-kidney Fibrotic Agent from the Marine-Derived SCSIO 41444. |
| topic | Aspergillus Humans Molecular Structure Alkaloids Animals Indole Alkaloids Marine Biology Quinazolines Fibrosis Kidney |
| url | https://pubmed.ncbi.nlm.nih.gov/41711189/ |