Synthesis and discovery of new compounds bearing coumarin scaffold for the treatment of pulmonary fibrosis

Deng, Dexin; Pei, Heying; Lan, Tingxuan; Zhu, Jiali; Tang, Minghai; Xue, Linlin; Yang, Zhuang; Zheng, Shoujun; Ye, Haoyu; Chen, Lijuan

doi:10.1016/j.ejmech.2019.111790

Cited by 7 publications

(2 citation statements)

References 31 publications

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“…Trichocarboline D ( 4 ) was not evaluated for its activity due to insufficient quantity. The Sirius red dye staining, which has been accepted to be an effective and convenient method for the anti-fibrotic screening model in vitro ( Deng et al, 2020 ; Xue et al, 2020 ), was then used to evaluate compound inhibitory activity on total collagen accumulation induced by TGF-β1. Pirfenidone was used as a positive control.…”

Section: Resultsmentioning

confidence: 99%

β-Carboline Alkaloids From the Deep-Sea Fungus Trichoderma sp. MCCC 3A01244 as a New Type of Anti-pulmonary Fibrosis Agent That Inhibits TGF-β/Smad Signaling Pathway

Hao

Chen

et al. 2022

Front. Microbiol.

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Pulmonary fibrosis is a scarring disease of lung tissue, which seriously threatens human health. Treatment options are currently limited, and effective strategies are still lacking. In the present study, 25 compounds were isolated from the deep-sea fungus Trichoderma sp. MCCC 3A01244. Among them, two β-carboline alkaloids, trichocarbolines A (1) and C (4) are new compounds. The chemical structures of these compounds were elucidated based on their HRESIMS, 1D and 2D NMR spectra, optical rotation calculation, and comparisons with data reported in the literature. Trichocarboline B [(+)- and (–)-enantiomers] had previously been synthesized, and this is its first report as a natural product. Their anti-pulmonary fibrosis (PF) activity and cytotoxicity were investigated. Compounds 1, 11, and 13 strongly inhibited TGF-β1-induced total collagen accumulation and showed low cytotoxicity against the HFL1 cell line. Further studies revealed compound 1 inhibited extracellular matrix (ECM) deposition by downregulating the expression of protein fibronectin (FN), proliferating cell nuclear antigen (PCNA), and α-smooth muscle actin (α-SMA). Mechanistic study revealed that compound 1 decreased pulmonary fibrosis by inhibiting the TGF-β/Smad signaling pathway. As a newly identified β-carboline alkaloid, compound 1 may be used as a lead compound for developing more efficient anti-pulmonary fibrosis agents.

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Section: Resultsmentioning

confidence: 99%

β-Carboline Alkaloids From the Deep-Sea Fungus Trichoderma sp. MCCC 3A01244 as a New Type of Anti-pulmonary Fibrosis Agent That Inhibits TGF-β/Smad Signaling Pathway

Hao

Chen

et al. 2022

Front. Microbiol.

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“…To evaluate the compounds’ inhibitory activity on TGF-β1-induced total collagen accumulation, the Sirius red dye staining, which has been accepted to be an effective and convenient method for the anti-fibrotic screening model in vitro [ 13 , 23 ], was used. Among the compounds tested, compounds 1 , 4 , and 7 showed good inhibition of collagen accumulation (60.44%, 57.37%, and 44.96%) in HFL1 cells ( Table 2 and Figure 4 B).…”

Section: Resultsmentioning

confidence: 99%

Exophilone, a Tetrahydrocarbazol-1-one Analogue with Anti-Pulmonary Fibrosis Activity from the Deep-Sea Fungus Exophiala oligosperma MCCC 3A01264

et al. 2022

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A new compound, exophilone (1), together with nine known compounds (2–10), were isolated from a deep-sea-derived fungus, Exophiala oligosperma. Their chemical structures, including the absolute configuration of 1, 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 1, 4, and 7 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 1, 4, and 7 showed low cytotoxicity against the HFL1 cell line. Particularly, exophilone (1) 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 (1) binds to both TGF-β1 and its receptor through hydrogen bonding interactions. Thus, exophilone (1) was identified as a promising anti-pulmonary fibrosis agent. It has the potential to be developed as a drug candidate for pulmonary fibrosis.

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4-Oxycoumarinyl linked acetohydrazide Schiff bases as potent urease inhibitors

Naz

Kanwal

Latif

et al. 2020

Bioorganic Chemistry

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Synthesis and discovery of new compounds bearing coumarin scaffold for the treatment of pulmonary fibrosis

Cited by 7 publications

References 31 publications

β-Carboline Alkaloids From the Deep-Sea Fungus Trichoderma sp. MCCC 3A01244 as a New Type of Anti-pulmonary Fibrosis Agent That Inhibits TGF-β/Smad Signaling Pathway

β-Carboline Alkaloids From the Deep-Sea Fungus Trichoderma sp. MCCC 3A01244 as a New Type of Anti-pulmonary Fibrosis Agent That Inhibits TGF-β/Smad Signaling Pathway

Exophilone, a Tetrahydrocarbazol-1-one Analogue with Anti-Pulmonary Fibrosis Activity from the Deep-Sea Fungus Exophiala oligosperma MCCC 3A01264

4-Oxycoumarinyl linked acetohydrazide Schiff bases as potent urease inhibitors

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