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Exophilone, a Tetrahydrocarbazol-1-one Analogue with Anti-Pulmonary Fibrosis Activity from the Deep-Sea Fungus <i>Exophiala oligosperma</i> MCCC 3A01264
oleh: Ming-Jun Hong, Meng-Jiao Hao, Guang-Yu Zhang, Hou-Jin Li, Zong-Ze Shao, Xiu-Pian Liu, Wen-Zhe Ma, Jun Xu, Taifo Mahmud, Wen-Jian Lan
Format: | Article |
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Diterbitkan: | MDPI AG 2022-07-01 |
Deskripsi
A new compound, exophilone (<b>1</b>), together with nine known compounds (<b>2</b>–<b>10</b>), were isolated from a deep-sea-derived fungus, <i>Exophiala oligosperma</i>. Their chemical structures, including the absolute configuration of <b>1,</b> were elucidated using nuclear magnetic resonance (NMR) spectroscopy, high-resolution electrospray ionization mass spectroscopy (HRESIMS), and electronic circular dichroism (ECD) calculation. Compounds were preliminarily screened for their ability to inhibit collagen accumulation. Compounds <b>1</b>, <b>4</b>, and <b>7</b> showed weaker inhibition of TGF-β1-induced total collagen accumulation in compared with pirfenidone (73.14% inhibition rate). However, pirfenidone exhibited cytotoxicity (77.57% survival rate), while compounds <b>1</b>, <b>4</b>, and <b>7</b> showed low cytotoxicity against the HFL1 cell line. Particularly, exophilone (<b>1</b>) showed moderate collagen deposition inhibition effect (60.44% inhibition rate) and low toxicity in HFL1 cells (98.14% survival rate) at a concentration of 10 μM. A molecular docking study suggests that exophilone (<b>1</b>) binds to both TGF-β1 and its receptor through hydrogen bonding interactions. Thus, exophilone (<b>1</b>) was identified as a promising anti-pulmonary fibrosis agent. It has the potential to be developed as a drug candidate for pulmonary fibrosis.