Cladocoran A and B:  Two Novel γ-Hydroxybutenolide Sesterterpenes from the Mediterranean Coral <i>Cladocora cespitosa</i>

Fontana, Angelo; Ciavatta, M. L.; Cimino, Guido

doi:10.1021/jo971586j

Cited by 38 publications

(30 citation statements)

References 16 publications

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“…353 A Vanuatuan collection of an Axinella species yielded the tetracyclic diterpene N-formyl-7-amino-11cycloamphilectene 393. 433 The structures proposed for cladocorans A 616 and B 617, isolated from the Mediterranean anthozoan Cladocora cespitosa, 434 are in question as spectroscopic data of synthetic material were not identical to data reported for the natural products. 355 In the same report are also described the isolation of an additional seven pyrrolosesterterpenoids 396-402, five furanosesterterpenoids 403-407, and two trinorsesterterpenoids 408 and 409 which had varying levels of cytotoxicity.…”

Section: Spongesmentioning

confidence: 99%

Marine natural products

et al. 2004

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This review covers the literature published in 2002 for marine natural products, with 579 citations (413 for the period January to December 2002) referring to compounds isolated from marine microorganisms and phytoplankton, green algae, brown algae, red algae, sponges, coelenterates, bryozoans, molluscs, tunicates and echinoderms. The emphasis is on new compounds (677 for 2002), together with their relevant biological activities, source organisms and country of origin. Syntheses that lead to the revision of structures or stereochemistries have been included (114), including any first total syntheses of a marine natural product.

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Section: Spongesmentioning

confidence: 99%

Marine natural products

et al. 2004

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“…Phospholipase A 2 (PLA 2 ) is responsible for the release of arachidonic acid from the cell membrane [ 26 ] and are classified as cytosolic (cPLA 2 ), intracellular (iPLA 2 ), [ 27 ] and secretory PLA 2 (sPLA 2 ), [ 28 ] Sessile organisms, like sponges, produce terpenoids capable of acting on PLA 2, which, therefore, have been extensively studied. [ 29 ] Our group has been working on marine‐derived compounds like bolinaquinone (BLQ, 6 ), [ 2c,30 ] cladocoran A (CLD A, 7 ) [ 2d,31 ] and scalaradial (SDL, 8 ) [ 2g ] acting as PLA 2 inhibitors (Figure 9).…”

Section: Rationalization Of the Biological Activity Of Nps By The mentioning

confidence: 99%

“…[ 33 ] This is a sesterterpene γ‐hydroxybutenolide extracted from Cladocora cespitosa , a Mediterranean coral. [ 31,33,34 ] Using mass spectroscopy and molecular docking experiments, we were able to find that CLD A not only binds to the enzyme catalytic site, which remains the preferential binding site but also to an allosteric site on the protein surface. [ 2d ] In particular, hydrophobic contacts are the driving force of the interaction with the target, along with hydrogen bonds with Lys62 and Gly29.…”

Section: Rationalization Of the Biological Activity Of Nps By The mentioning

confidence: 99%

From Natural Compounds to Bioactive Molecules through NMR and In Silico Methodologies

et al. 2020

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Marine and terrestrial organisms are an unlimited source of active secondary metabolites. They are characterized by high chemical diversity, biochemical specificity, and other molecular features that make them a valid starting point for lead generation in the drug discovery process. Considering the complex structural architecture and the high number of stereogenic centers, compared to the synthetic drugs, the elucidation of the 2D structure and the assessment of the precise 3D arrangements of natural products (NPs) provide essential insights into ligand‐target interaction which can drive a rational lead optimization process. In this regard, the combination of NMR spectroscopy with modern computational techniques represents one of the most effective approaches to achieve this task. The DFT/NMR integrated method, and its application, in combination with the accurate ROE‐distance analysis, have been employed as valid support, both to clarify the configuration and conformational profile of the active secondary metabolites and to shed more light on the molecular basis of their mechanism of action. Indeed, the comprehension at a molecular level of their interactions with specific targets involved in pathologies, like inflammation and cancer, represents a cornerstone for further investigations through computational tools like molecular docking and molecular dynamics. These high‐efficiency in silico techniques play a crucial part in the drug discovery process as well as in lead optimization procedures. Furthermore, this integrated approach provides the identification of novel chemical platforms disclosing new bioactive molecules with enhanced potency and selectivity.

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“…[17] Cladocoran A (CLD A) is a member of the sesterterpenoid ghydroxybutenolides with a unique carbon skeleton, isolated from the Mediterranean coral Cladocora cespitosa by Fontana et al, together with its C-18 deacetylated congener (CLD B). [18][19][20] CLD A is endowed with a high sPLA 2 inhibitory effect, comparable to that of manoalide, with an IC 50 of 0.78(AE0.06) mm. [18] On this basis, we were interested to disclose the CLD A mechanism of action on our target enzyme sPLA 2 -IIA.…”

Section: Introductionmentioning

confidence: 98%

The Binding Mode of Cladocoran A to the Human Group IIA Phospholipase A₂

et al. 2011

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The molecular basis for human group IIA phospholipase A(2) inactivation by the marine natural product cladocoran A (CLD A) has been studied in order to elucidate its relevant anti-inflammatory properties. Indeed, secretory phospholipases A(2) are well-known to be implicated in the pathogenesis of inflammation, such as rheumatoid arthritis, septic shock, psoriasis and asthma, thus the understanding of their inactivation mechanism could be useful for the development of new chemical classes of selective inhibitors. Our results, collected by a combination of biochemical approaches, advanced mass spectrometry and molecular modeling, suggest a competitive inhibition mechanism guided by a noncovalent molecular recognition event, and disclose the key role of the CLD A γ-hydroxybutenolide ring in the chelation of the catalytic calcium ion inside the enzyme active site. Moreover, CLD A is able to react selectively with Ser82, although this covalent event seems to play a secondary role in terms of enzyme inhibition.

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Cladocoran A and B: Two Novel γ-Hydroxybutenolide Sesterterpenes from the Mediterranean Coral Cladocora cespitosa

Cited by 38 publications

References 16 publications

Marine natural products

Marine natural products

From Natural Compounds to Bioactive Molecules through NMR and In Silico Methodologies

The Binding Mode of Cladocoran A to the Human Group IIA Phospholipase A₂

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Cladocoran A and B: Two Novel γ-Hydroxybutenolide Sesterterpenes from the Mediterranean Coral Cladocora cespitosa

Cited by 38 publications

References 16 publications

Marine natural products

Marine natural products

From Natural Compounds to Bioactive Molecules through NMR and In Silico Methodologies

The Binding Mode of Cladocoran A to the Human Group IIA Phospholipase A2

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The Binding Mode of Cladocoran A to the Human Group IIA Phospholipase A₂