Cytotoxic pyridine alkaloids from a marine-derived fungus Arthrinium arundinis exhibiting apoptosis-inducing activities against small cell lung cancer

• Published in: Phytochemistry (Oxford) 2023-09, Vol.213, p.113765-113765, Article 113765
• Main Authors: Hu, Yiwei, Ma, Shuai, Pang, Xiaoyan, Cong, Mengjing, Liu, Qianqian, Han, Fanghai, Wang, Junjian, Feng, Weineng, Liu, Yonghong, Wang, Junfeng
• Format: Article
• Language: English
• Subjects: Alkaloids - chemistry; Antineoplastic Agents - chemistry; Apoptosis; Arthrinium arundinis; Ascomycota - chemistry; Carcinoma, Non-Small-Cell Lung; Cytotoxic; Humans; Lung Neoplasms - drug therapy; Molecular networking; Molecular Structure; Pyridine alkaloids; Pyridines; Pyridones - chemistry; Pyridones - pharmacology; Tandem Mass Spectrometry
• ISSN: 0031-9422; 1873-3700
• DOI: 10.1016/j.phytochem.2023.113765

Small cell lung cancer (SCLC) is a kind of high-grade neuroendocrine carcinoma, which is characterized by a higher proliferative rate, earlier metastasis and more poor outcomes compared to non-small cell lung cancer (NSCLC). Under the guidance of MS/MS based molecular networking, three undescribed pyridone alkaloids, namely, arthpyrones M–O (1–3), together with two known pyridone derivatives, arthpyrones C (4) and G (5), were isolated from a sponge-derived Arthrinium arundinis. Their structures were determined through extensive spectroscopic analysis, ECD calculations, and X-ray single-crystal diffraction. Arthpyrone M (1) possessed a novel cage structure bearing an ether bridge functionality rarely reported in this class of metabolites. All isolated compounds were evaluated for their cytotoxicities against five cancer cell lines. As a result, compounds 1–5 showed cytotoxicity against some or all of the five cancer cell lines with IC50 values ranging from 0.26 to 6.43 μM. Among them, arthpyrone O (3) not only exhibited potent efficacy against the proliferative activity of SCLC cells and induced apoptosis in vitro, but also significantly inhibited the growth of xenograft tumor based on SCLC cells in vivo, which indicated 4-hydroxy-2-pyridone alkaloids might been revised as privileged scaffolds in drug discovery. [Display omitted] •Arthpyrones M–O, were isolated from a sponge-derived Arthrinium arundinis.•Arthpyrone M possessed a novel cage structure bearing an ether bridge functionality rarely reported in this class of metabolites.•Their absolute configurations were determined by ECD calculations and X-ray single-crystal diffraction.•Arthpyrone O significantly suppressed the growth of SCLC cells in vitro and in vivo.