Design, synthesis and biological evaluation of novel asperphenamate derivatives

Liu, Qingyin; Li, Wei; Sheng, Lei; Zou, Chunyang; Sun, Hongbin; Zhang, Chunfeng; Liu, Yang; Shi, Jiyue; Ma, Enlong; Liu, Yuan

doi:10.1016/j.ejmech.2016.01.020

Cited by 14 publications

(6 citation statements)

References 25 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%

“…Based on the two latter shifts and their multiplets, they were assigned as H-5 and H-7, respectively, with δ H 7.94 (m) assigned at H-3, and the H-4 shift assigned to the general aromatic region at 7.18-7.35, led to confirmation of pyridinecarboxylic acid moiety as nicotinic acid. This fits with the published NMR data for nicotinic acid (Chen et al, 1999) and the corresponding synthetic asperphenamate analog (Liu et al, 2016).…”

Section: Nmr Confirms Phenylalanine Exchange For Other Amino Acids In the Non-reduced N-benzoyl Amino Acid Moietysupporting

confidence: 89%

“…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: Nmr Confirms Phenylalanine Exchange For Other Amino Acids In the Non-reduced N-benzoyl Amino Acid Moietysupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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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“…Another typical feature of autophagy is the accumulation of the acidic autophagic vacuoles (AVOs) 45,46 . To verify the development of AVOs, Acridine Orange (AO) staining was used to examine whether the acidic vesicular organelles in SGC-7901 cells were increased.…”

Section: Induces Autophagymentioning

confidence: 99%

Design, synthesis and anticancer activity of naphthoquinone derivatives

Shen

Wang

Han

et al. 2020

Journal of Enzyme Inhibition and Medicinal Chemistry

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Basis on molecular docking and pharmacophore analysis of naphthoquinone moiety, a total of 23 compounds were designed and synthesised. With the help of reverse targets searching, anti-cancer activity was preliminarily evaluated, most of them are effective against some tumour cells, especially compound 12: 1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl-4-oxo-4-((4-phenoxyphenyl)amino) butanoate whose IC 50 against SGC-7901 was 4.1 ± 2.6 lM. Meanwhile the anticancer mechanism of compound 12 had been investigated by AnnexinV/PI staining, immunofluorescence, Western blot assay and molecular docking. The results indicated that this compound might induce cell apoptosis and cell autophagy through regulating the PI3K signal pathway.

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“…Previous studies have shown that xanthoepocin inhibits the growth of S. aureus and S. aureus MRSA with MICs of 1.56 µg/mL [ 47 ]. Although asperphenamate is well known for its antitumor activity [ 50 , 51 ], it is inactive against the microorganisms tested ( S. aureus and MRSA) at up to 64 µg/mL [ 48 ]. Combining all these results, but recognizing that our putative MS-based molecular networking annotation has to be taken with caution, P. olsonii UBOCC-A-118169 and P. olsonii UBOCC-A-119011 may produce xanthoepocin-like molecules as antibacterial secondary metabolites.…”

Section: Resultsmentioning

confidence: 99%

Highlighting the Biotechnological Potential of Deep Oceanic Crust Fungi through the Prism of Their Antimicrobial Activity

et al. 2021

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Among the different tools to address the antibiotic resistance crisis, bioprospecting in complex uncharted habitats to detect novel microorganisms putatively producing original antimicrobial compounds can definitely increase the current therapeutic arsenal of antibiotics. Fungi from numerous habitats have been widely screened for their ability to express specific biosynthetic gene clusters (BGCs) involved in the synthesis of antimicrobial compounds. Here, a collection of unique 75 deep oceanic crust fungi was screened to evaluate their biotechnological potential through the prism of their antimicrobial activity using a polyphasic approach. After a first genetic screening to detect specific BGCs, a second step consisted of an antimicrobial screening that tested the most promising isolates against 11 microbial targets. Here, 12 fungal isolates showed at least one antibacterial and/or antifungal activity (static or lytic) against human pathogens. This analysis also revealed that Staphylococcus aureus ATCC 25923 and Enterococcus faecalis CIP A 186 were the most impacted, followed by Pseudomonas aeruginosa ATCC 27853. A specific focus on three fungal isolates allowed us to detect interesting activity of crude extracts against multidrug-resistant Staphylococcus aureus. Finally, complementary mass spectrometry (MS)-based molecular networking analyses were performed to putatively assign the fungal metabolites and raise hypotheses to link them to the observed antimicrobial activities.

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Design, synthesis and biological evaluation of novel asperphenamate derivatives

Cited by 14 publications

References 25 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

Design, synthesis and anticancer activity of naphthoquinone derivatives

Highlighting the Biotechnological Potential of Deep Oceanic Crust Fungi through the Prism of Their Antimicrobial Activity

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