A novel cathepsin L inhibitor prevents the progression of idiopathic pulmonary fibrosis

Liu, Yuan; Zou, Chunyang; Ge, Wentao; Liu, Yutong; Hu, Baichun; Wang, Jian; Lin, Bin; Li, Yanchun; Ma, Enlong

doi:10.1016/j.bioorg.2019.103417

Cited by 21 publications

(12 citation statements)

References 32 publications

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“…Moreover, asperphenidine F1, was the only active candidate against the pancreas cell line, suggesting the nicotinic acid analogs being more active than the benzoic acid analogs. Although our cytotoxicity results for asperphenamates F and Y, as well as asperphenidine F1 are comparable to the previously published data, none of them show improved bioactivity compared to synthetic asperphenamate derivatives (Li et al, 2012;Yuan et al, 2012Yuan et al, , 2018Yuan et al, , 2019Yuan et al, , 2020Liu et al, 2016Liu et al, , 2018.…”

Section: Discussionsupporting

confidence: 85%

“…Additionally, the compound has also been isolated in trace amounts from a number of unrelated plant species (Wu et al, 2004;Dang et al, 2014;Zhou et al, 2017;Bunteang et al, 2018;Caridade et al, 2018), suggesting endophytic fungi being the actual producers, rather than the plants. Although asperphenamate is mainly known for its antitumour activity and immense synthetic chemists interest in asperphenamate backbone modification (Li et al, 2012;Yuan et al, 2012Yuan et al, , 2018Yuan et al, , 2019Yuan et al, , 2020Liu et al, 2016), recent studies have also shown asperphenamate to be a potential neuroinflamatory inhibitor (Zhou et al, 2017), and to possess anti-HIV (Bunteang et al, 2018) and antidiabetic (Del Valle et al, 2016) properties. In recent years, a handful of new natural analogs have been isolated, namely Asperphenamates B (4) and C (5) (Liu et al, 2018), and 4-OMe-asperphenamate (Zheng et al, 2013;Ratnaweera et al, 2016) (6) from filamentous fungi.…”

Section: Introductionmentioning

confidence: 99%

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Mass Spectrometry Guided Discovery and Design of Novel Asperphenamate Analogs From Penicillium astrolabium Reveals an Extraordinary NRPS Flexibility

et al. 2021

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Asperphenamate is a small peptide natural product that has gained much interest due to its antitumor activity. In the recent years numerous bioactive synthetic asperphenamate analogs have been reported, whereas only a handful of natural analogs either of microbial or plant origin has been discovered. Herein we describe a UHPLC-HRMS/MS and amino acid supplement approach for discovery and design of novel asperphenamate analogs. Chemical analysis of Penicillium astrolabium, a prolific producer of asperphenamate, revealed three previously described and two novel asperphenamate analogs produced in significant amounts, suggesting a potential for biosynthesis of further asperphenamate analogs by varying the amino acid availability. Subsequent growth on proteogenic and non-proteogenic amino acid enriched media, revealed a series of novel asperphenamate analogs, including single or double amino acid exchange, as well as benzoic acid exchange for nicotinic acid, with the latter observed from a natural source for the first time. In total, 22 new asperphenamate analogs were characterized by HRMS/MS, with one additionally confirmed by isolation and NMR structure elucidation. This study indicates an extraordinary nonribosomal peptide synthetase (NRPS) flexibility based on substrate availability, and therefore the potential for manipulating and designing novel peptide natural products in filamentous fungi.

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Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Mass Spectrometry Guided Discovery and Design of Novel Asperphenamate Analogs From Penicillium astrolabium Reveals an Extraordinary NRPS Flexibility

et al. 2021

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“…Cathepsin L inhibitors prevent pulmonary fibrosis. This fact indicates the importance of Cathepsin L as a target for the treatment of SARS-CoV-2 [91] . A research study on HEK 293/hACE2 cells in which these cells were treated with specific Cathepsin L inhibitor demonstrated very low chances of SARS-CoV-2 entry to host cells.…”

Section: Host-based Druggable Targetmentioning

confidence: 96%

A perspective on potential target proteins of COVID-19: Comparison with SARS-CoV for designing new small molecules

Kumar

Chauhan

Kalra

et al. 2020

Bioorganic Chemistry

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“…Fujishima et al has demonstrated that the structural differences between cathepsin L and cathepsin B, where the S' subsites of the both two enzymes to be totally different. They have also found that The S2 pocket of cathepsin L to be superficial and different from cathepsin B [109] and it will help to design the specific and effective inhibitors. However, the cathepsin L inhibitors may serve as a therapeutic choice for SARS-CoV-2 and drug design using this enzyme may prevent the progression of pulmonary fibrosis [110].…”

Section: Cathepsin Lmentioning

confidence: 99%

SARS-CoV-2 protein drug targets landscape: a potential pharmacological insight view for the new drug development

Chakraborty

Bhattacharya

Mallick

et al. 2021

Expert Review of Clinical Pharmacology

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Introduction: Protein drug targets play a significant choice in different stages of the drug discovery process. There is an urgent need to understand the drug discovery approaches and protein drug targets (PDT) of SARS-CoV-2, with structural insights for the development of SARS-CoV-2 drugs through targeted therapeutic approach. Areas covered: We have described the protein as a drug target class and also discussed various drug discovery approaches for SARS-CoV-2 involving the protein drug targets such as drug repurposing study, designing of viral entry inhibitors, viral replication inhibitors, and different enzymes of the virus. We have performed comprehensive literature search from the popular databases such as PubMed Google scholar, Web of Science, and Scopus. Finally, we have illustrated the structural landscape of different significant viral proteins (3 CLpro or Mpro, PLpro, RdRp, helicase, S protein) and host proteins as drug targets (cathepsin L, furin, TMPRSS2, ACE2). Expert opinion: The structural landscape of PDT with their binding pockets, and significant residues involved in binding has been discussed further to better understand the PDT and the structure-based drug discovery for SARS-CoV-2. This attempt will increase more therapeutic options, and combination therapies with a multi-target strategy.

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A novel cathepsin L inhibitor prevents the progression of idiopathic pulmonary fibrosis

Cited by 21 publications

References 32 publications

Mass Spectrometry Guided Discovery and Design of Novel Asperphenamate Analogs From Penicillium astrolabium Reveals an Extraordinary NRPS Flexibility

Mass Spectrometry Guided Discovery and Design of Novel Asperphenamate Analogs From Penicillium astrolabium Reveals an Extraordinary NRPS Flexibility

A perspective on potential target proteins of COVID-19: Comparison with SARS-CoV for designing new small molecules

SARS-CoV-2 protein drug targets landscape: a potential pharmacological insight view for the new drug development

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