Pseudotheonamides, Serine Protease Inhibitors from the Marine Sponge <i>Theonella swinhoei</i><sup>1</sup>

Nakao, Youichi; Masuda, Akito; Matsunaga, Shigeki; Fusetani, Nobuhiro

doi:10.1021/ja9831195

Cited by 51 publications

(36 citation statements)

References 16 publications

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“…In fact, the conjugate bond is located at a distance of about 4 Å from Cys145, suggesting that both pseudotheonamides (12 and 17) could form a covalent bond with Cys145. These pseudotheonamides have been isolated from the marine sponge Theonella swinhoei and have shown good inhibitory activity on the serine protease [27]. Consequently, after having covalently linked the compounds 12 and 17 with the Cys145 residue, a short (2 ns) MD simulation was performed in order to stabilize the new complex.…”

Section: $$mentioning

confidence: 99%

Putative Inhibitors of SARS-CoV-2 Main Protease from A Library of Marine Natural Products: A Virtual Screening and Molecular Modeling Study

et al. 2020

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The current emergency due to the worldwide spread of the COVID-19 caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a great concern for global public health. Already in the past, the outbreak of severe acute respiratory syndrome (SARS) in 2003 and Middle Eastern respiratory syndrome (MERS) in 2012 demonstrates the potential of coronaviruses to cross-species borders and further underlines the importance of identifying new-targeted drugs. An ideal antiviral agent should target essential proteins involved in the lifecycle of SARS-CoV. Currently, some HIV protease inhibitors (i.e., Lopinavir) are proposed for the treatment of COVID-19, although their effectiveness has not yet been assessed. The main protease (M pro ) provides a highly validated pharmacological target for the discovery and design of inhibitors. We identified potent M pro inhibitors employing computational techniques that entail the screening of a Marine Natural Product (MNP) library. MNP library was screened by a hyphenated pharmacophore model, and molecular docking approaches. Molecular dynamics and re-docking further confirmed the results obtained by structure-based techniques and allowed this study to highlight some crucial aspects. Seventeen potential SARS-CoV-2 M pro inhibitors have been identified among the natural substances of marine origin. As these compounds were extensively validated by a consensus approach and by molecular dynamics, the likelihood that at least one of these compounds could be bioactive is excellent.

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Section: $$mentioning

confidence: 99%

Putative Inhibitors of SARS-CoV-2 Main Protease from A Library of Marine Natural Products: A Virtual Screening and Molecular Modeling Study

et al. 2020

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“…also inhibited two proteases thrombin (IC50 = 5.2 -13 nM) and trypsin (IC50 = 7.4 -370 nM) [54,55]. Interestingly, other compounds from the same sponge species Theonella swinhoei such as nazumazoles, pseudotheonamides, dihydrocyclotheonamide A showed inhibitory activity against proteases (e.g., thrombin, RCE-protease, chymotrypsin) [65,70]. To date, many new compounds extracted from various sponge have been known as protease inhibitors (see Table 3), indicating that marine sponge is one of the potential sources for mining protease inhibitors.…”

Section: Protease Inhibitors From Sponge and Spong-associated Microormentioning

confidence: 98%

Mini-Review PROTEASE INHIBITOR (PI) AND PIs FROM SPONGE-ASSOCIATED MICROORGANISMS

Hong¹,

Dat²,

Cúc³

et al. 2018

JST

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Protease inhibitors (PIs) are proteins or peptides inhibiting the activity of protease and constitute a very important mechanism for regulating protease activity. So far, PIs have been used for the study of enzyme structures and reaction mechanisms, but recently they have been used in pharmaceutical, agricultural and industrial fields. Compared to terrestrial counterparts, marine environment possesses their unique characters, therefore, they are capable of producing a wide range of novel bioactive compounds including protease inhibitors. In our review, a brief overview of protease inhibitors (e.g., classification, mechanisms, and characteristics of PIs) and protease inhibitors from marine sponges and sponge-associated microorganisms has been reviewed.

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“…The ability of the cyclotheonamides to inhibit serine proteases was explained by the presence of the R-keto group in the K-Arg residue [45]. In the search for new inhibitors of serine proteases by the authors of [46] six new peptides, pseudotheonamides, related to the cyclotheonamides 19, were isolated from the Theonella swinhoei sponges (also from the Hachijojima Island). Five of them were linear (not discussed in the present review).…”

Section: Cyclic Peptides With Fragments Of αβ-Diamino Acidsmentioning

confidence: 99%

“…The sixth was dihydrocyclotheonamide A (20), which differs from the cyclotheonamides only by one reduced keto group and therefore has a (2R,3S)-β-amino-α-hydroxy acid fragment in the ring as well as (2S)-α,β-diaminopropionic acid. Compound 20 is a thrombin inhibitor [46] Representatives of bicyclic polypeptides aciculitins A-C (21), isolated from the marine sponge Aciculitis orientalis and containing the fragment of an unusual histidinetyrosine bridge, were described [47]. These bicycles were the first glycosylated (at the phenolic hydroxy group) cyclopeptides isolated from marine organisms.…”

Section: Cyclic Peptides With Fragments Of αβ-Diamino Acidsmentioning

confidence: 99%

Biologically active cyclic polypeptides with fragments of β-amino acid derivatives isolated from marine organisms (review)

Romanova

Tallo

Rybalko

et al. 2011

Chem Heterocycl Comp

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Published data on the structure, stereochemistry, and biological activity of natural cyclic polypeptides containing fragments of β-amino acids are reviewed, and an attempt is made to relate the structure to the biological activity.According to available estimates [1], there are more β-amino acids in the nature than the 22 proteinogenic α-amino acids that take part in ribosomal protein synthesis. The β-amino acids exist either as such or as fragments of the molecules of natural compounds with various degrees of complexity [2] and most often as linear or cyclic peptides that are, in all probability, formed by such microorganisms as bacteria and fungi as a result of non-ribosomal protein synthesis [3].Before 1996 nothing was known about the structure of the simplest β-peptides in the crystal and in solution. Today there are numerous papers and reviews on natural, semisynthetic, and fully synthetic β-peptides, the most comprehensive of which are the papers [4][5][6]. For this reason we will not dwell on these aspects here.The aim of our review is to classify published data on the structure, stereochemistry, and biological activity and also to study the structure-activity relationship of cyclic β-peptides, which have shown greater resistance to the action of enzymes than their linear analogs and α-peptides and therefore exhibit biological selectivity.

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Pseudotheonamides, Serine Protease Inhibitors from the Marine Sponge Theonella swinhoei¹

Cited by 51 publications

References 16 publications

Putative Inhibitors of SARS-CoV-2 Main Protease from A Library of Marine Natural Products: A Virtual Screening and Molecular Modeling Study

Putative Inhibitors of SARS-CoV-2 Main Protease from A Library of Marine Natural Products: A Virtual Screening and Molecular Modeling Study

Mini-Review PROTEASE INHIBITOR (PI) AND PIs FROM SPONGE-ASSOCIATED MICROORGANISMS

Biologically active cyclic polypeptides with fragments of β-amino acid derivatives isolated from marine organisms (review)

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Pseudotheonamides, Serine Protease Inhibitors from the Marine Sponge Theonella swinhoei1

Cited by 51 publications

References 16 publications

Putative Inhibitors of SARS-CoV-2 Main Protease from A Library of Marine Natural Products: A Virtual Screening and Molecular Modeling Study

Putative Inhibitors of SARS-CoV-2 Main Protease from A Library of Marine Natural Products: A Virtual Screening and Molecular Modeling Study

Mini-Review PROTEASE INHIBITOR (PI) AND PIs FROM SPONGE-ASSOCIATED MICROORGANISMS

Biologically active cyclic polypeptides with fragments of β-amino acid derivatives isolated from marine organisms (review)

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Pseudotheonamides, Serine Protease Inhibitors from the Marine Sponge Theonella swinhoei¹