Xenicane Diterpenes Research Articles

4-Hydroxydictyolactone alleviates cerebral ischemia injury by regulating neuroinflammation and autophagy via AMPK signaling pathway

BackgroundCerebral ischemia (CI), a cerebrovascular disorder, is a major contributor to disability and mortality. Marine-derived compounds are an important source of new neuroprotective drug candidates. Xenicane-type diterpenes from brown algae of the genus Dictyota have exhibited potential neuroprotective effects against CI injury, attributed to their antioxidant properties. However, whether there are other underlying neuroprotective mechanisms of xenicane diterpenes against CI is still ambiguous. PurposeThis study aims to elucidate the neuroprotective efficacy and mechanism of 4-hydroxydictyolactone (HDTL) in the treatment of CI. MethodsThe LPS-induced BV2 cell model was used for anti-neuroinflammatory activity assay. Tandem Mass Tag (TMT)-based quantitative proteomics was employed to identify underlying mechanisms. The OGD/R-induced SH-SY5Y cell model and a MCAO mice model were used to assess the neuroprotective effect of HDTL against CI in vitro and in vivo. ResultsHDTL reduced inflammation in LPS-stimulated BV2 cells by inhibiting the IKK/IκB/NF-κB pathway and by enhancing AMPK phosphorylation. Additionally, in SH-SY5Y cells treated with OGD/R, HDTL facilitated autophagy and reduced apoptosis. The neuroprotective properties of HDTL were abrogated in AMPK- silenced SH-SY5Y cells. In MCAO mice, HDTL ameliorated CI injury as evidenced by decreases in neurological deficit scores and cerebral infarction. HDTL also promoted autophagy and reduced apoptosis in vivo through both the AMPK/mTOR and IKK/IκB/NF-κB pathways. ConclusionHDTL exhibits neuroprotective effects through regulating the AMPK/mTOR and IKK/IκB/NF-κB pathways. These findings suggest that HDTL is a promising therapeutic candidate for CI treatment.

Transient Receptor Potential Melastatin 7 (TRPM7) Ion Channel Inhibitors: Preliminary SAR and Conformational Studies of Xenicane Diterpenoids from the Hawaiian Soft Coral Sarcothelia edmondsoni.

Waixenicin A, a xenicane diterpene from the octocoral Sarcothelia edmondsoni, is a selective, potent inhibitor of the TRPM7 ion channel. To study the structure-activity relationship (SAR) of waixenicin A, we isolated and assayed related diterpenes from S. edmondsoni. In addition to known waixenicins A (1) and B (2), we purified six xenicane diterpenes, 7S,8S-epoxywaixenicins A (3) and B (4), 12-deacetylwaixenicin A (5), waixenicin E (6), waixenicin F (7), and 20-acetoxyxeniafaraunol B (8). We elucidated the structures of 3-8 by NMR and MS analyses. Compounds 1, 2, 3, 4, and 6 inhibited TRPM7 activity in a cell-based assay, while 5, 7, and 8 were inactive. A preliminary SAR emerged showing that alterations to the nine-membered ring of 1 did not reduce activity, while the 12-acetoxy group, in combination with the dihydropyran, appears to be necessary for TRPM7 inhibition. The bioactive compounds are proposed to be latent electrophiles by formation of a conjugated oxocarbenium ion intermediate. Whole-cell patch-clamp experiments demonstrated that waixenicin A inhibition is irreversible, consistent with a covalent inhibitor, and showed nanomolar potency for waixenicin B (2). Conformational analysis (DFT) of 1, 3, 7, and 8 revealed insights into the conformation of waixenicin A and congeners and provided information regarding the stabilization of the proposed pharmacophore.

Antioxidant and Neuroprotective Xenicane Diterpenes from the Brown Alga Dictyota coriacea.

Five new xenicane diterpenes, including three rare nitrogen-containing derivatives, dictyolactams A (1) and B (2) and 9-demethoxy-9-ethoxyjoalin (3), a rare diterpene with a cyclobutanone moiety, named 4-hydroxyisoacetylcoriacenone (4), and 19-O-acetyldictyodiol (5), were isolated from an East China Sea collection of the brown alga Dictyota coriacea, along with 15 known analogues (6-20). The structures of the new diterpenes were elucidated by spectroscopic analyses and theoretical ECD calculations. All compounds had cytoprotective effects against oxidative stress in neuron-like PC12 cells. The antioxidant mechanism of 18-acetoxy-6,7-epoxy-4-hydroxydictyo-19-al (6) was related to the activation of Nrf2/ARE signaling pathway; it also showed significant neuroprotective effects against cerebral ischemia-reperfusion injury (CIRI) in vivo. This study provided xenicane diterpene as a promising lead scaffold for the development of potent neuroprotective agents against CIRI.

Cytotoxic analogues of marine diterpenoid plumisclerin A by shifting the lipophilic branch on the characteristic tricyclic core.

Plumisclerin A is one of the most complex cytotoxic xenicane diterpenes from marine sources, featuring a unique congested and rigid tricyclo[4.3.1.01,5]decane core and a lipophilic acyl chain. This work explored a number of new analogues of plumisclerin A through modifying the characteristic tricyclo[4.3.1.01,5]decane core with lipophilic chains starting from a common lactone intermediate. Bioactivity examination of all the synthetic analogues shows that new analogues 2a, 18 and 21 exhibited comparable inhibitory potencies to that of the natural product against the proliferation of cancer cells. Structural comparison of these bioactive natural and unnatural compounds reveals that the location of lipophilic substituent(s) on the tricyclo[4.3.1.01,5]decane core is spatially flexible, and this work thus offers a new channel to diverse bioactive analogues of plumisclerin A.

Terpenoids from Marine Soft Coral of the Genus Xenia in 1977 to 2019.

Members of the marine soft coral genus Xenia are rich in a diversity of diterpenes. A total of 199 terpenes consisting of 14 sesquiterpenes, 180 diterpenes, and 5 steroids have been reported to date. Xenicane diterpenes were reported to be the most common chemical skeleton biosynthesized by members of this genus. Most of the literature reported the chemical diversity of Xenia collected from the coral reefs in the South China Sea and the coastal waters of Taiwan. Although there was a brief review on the terpenoids of Xenia in 2015, the present review is a comprehensive overview of the structural diversity of secondary metabolites isolated from soft coral genus Xenia and their potent biological activity as reported between 1977 to 2019.

ChemInform Abstract: New Xenicane and Hydroazulenoid Diterpenes from an Australian Collection of Dictyota divaricata

ChemInform Abstract: New Xenicane and Hydroazulenoid Diterpenes from an Australian Collection of Dictyota divaricata

ChemInform Abstract: Studies for the Synthesis of Xenicane Diterpenes. A Stereocontrolled Total Synthesis of 4‐Hydroxydictyolactone.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Studies for the Synthesis of Xenicane Diterpenes. A Stereocontrolled Total Synthesis of 4-Hydroxydictyolactone

The stereocontrolled total synthesis of 4-hydroxydictyolactone (4), a member of the xenicane diterpene family of natural products, is described. These studies feature the development of the B-alkyl Suzuki cross-coupling reaction for direct access to (E)-cyclononenes from acyclic precursors. The Ireland-Claisen rearrangement is effectively utilized to establish the backbone asymmetry of the contiguous C(2), C(3), C(10) stereotriad of 4. The synthesis strategy has devised an intramolecular Nozaki-Hiyama reductive allylation of a formate ester for the stereoselective formation of five-membered lactols 22. In addition, an internally directed S(E)' propargylation using allenylmagnesium bromide is described to establish the stereochemistry of the C(4) alcohol in 27, and the terminal alkyne is subsequently functionalized via a regioselective syn-silylstannylation to yield 30. Finally, the stereocontrolled phenylselenylation of the ester enolate derived from 43 leads to the desired syn-oxidative elimination to yield the natural product 4.

Studies for the synthesis of marine natural products

The process of allylic transposition in S(E)' reactions is a significant construct for synthesis. The flexibility of a variety of allylation strategies provides for the rational design of pathways to a diverse array of complex targets. Our recent studies of S(E)' reactions will examine issues of stereoselectivity and efficiency in the context of applications toward the synthesis of marine natural products such as the xenicane diterpenes, which feature the strained E-cyclononene ring system, and peloruside A, a 16-membered macrocyclic lactone.

Two new xeniolides from a Taiwanese Xenia soft coral

Chromatographic investigation of an extract of the octocoral Xenia umbellata afforded two new diterpenes, xenibelatols A (1) and B (2), in addition to three known xenicane diterpenes, 7,8-oxidoisoxeniolide (3), 9-hydroxyxeniolide F (4), and florlide C, and a cadinene sesquiterpene, xenitorin A (5). The structures were elucidated through spectroscopic analysis, especially 2D NMR.

Xenicane-Type Diterpenes with Cytotoxicity from Xenia florida

Chromatographic investigation of an acetone extract of the octocoral Xenia florida afforded three new xenicane diterpenes, namely, florxenilide A (1), florxenilide B (2), and florxenilide C (3), in addition to seven known xenicane diterpenes and two known cadinene sesquiterpenes. Structures were elucidated through spectroscopic analysis, especially 2D NMR, and chemical derivatization. The absolute configuration of 1 was determined by NOESY, CD, and Mosher's methods. Florxenilides A (1) and B (2) exhibited cytotoxicity against human colon cancer (WiDr) cells at 4.5 and 3.7 muM, respectively.

New xenicane diterpenes isolated from the acetone extract of the soft coral Xenia florida.

Six new xenicane diterpenes have been isolated from the acetone extract of the soft coral Xenia florida. Two of them are diterpenes containing a bicyclic [4.3.1] ring system. Three of them seem to be precursors for diterpenes possessing the bicyclic [4.3.1] ring system. One is a common monocarbocyclic diterpene with a cyclononane skeleton.

ChemInform Abstract: Antheliatin and Zahavins A and B, Three New Cytotoxic Xenicane Diterpenes from Two Soft Corals.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Antheliatin and Zahavins A and B, Three New Cytotoxic Xenicane Diterpenes from Two Soft Corals

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAntheliatin and Zahavins A and B, Three New Cytotoxic Xenicane Diterpenes from Two Soft CoralsA. Rudi, S. Ketzinel, I. Goldberg, Z. Stein, Y. Kashman, Yehuda Benayahu, and Michael SchleyerCite this: J. Nat. Prod. 1995, 58, 10, 1581–1586Publication Date (Print):October 1, 1995Publication History Published online1 July 2004Published inissue 1 October 1995https://doi.org/10.1021/np50124a016RIGHTS & PERMISSIONSArticle Views173Altmetric-Citations18LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (402 KB) Get e-Alerts Get e-Alerts

New Metabolites from the South African soft coral Capnella thyrsoidea

Ethyl acetate extracts of two phenotypic color variants of the endemic South African soft coral, Capnella thyrsoidea yielded the known steroid 5α-pregna-l,20-dien-3-one ( 1) and a further six new compounds, 16ß-hydroxy-5α-pregna-l,20-dien-3-one 16-acetate ( 2), 3α,16ß-dthydroxy-5α-pregna-1,20-diene 3,16-diacetate ( 3) and four xemcane diterpenes, the tsitsixenicins A-D ( 6, 10–12). Standard spectroscopic methods were used to determine the structures and stereochemistry of these compounds This is the first reported isolation of xenicane diterpenes from the soft coral family Nephtheiidae Compounds 6 and 10 inhibit Superoxide production m both rabbit and human cell neutrophils.

ChemInform Abstract: Xenicane Diterpenes Revisited: Thermal (E) → (Z) Isomerization and Conformational Motions. A Unifying Picture.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Xenicane Diterpenes Revisited: Thermal (E)→(Z) isomerization and conformational motions. A unifying picture

AbstractKinetic and equilibrium studies show that typical xenicanes such as dictyolactone (1) and 4‐hydroxydictyolactone (3) undergo slow conformation medium‐ring flipping between the predominant trans‐(1a or 3a; Me(20) trans to H–C(3)) and the minor cis‐conformers (1b or 3b; Me(20) cis to H–C(3); see Scheme 1). The formation of the latter is inhibited in heterocyclic‐ring‐opened congeners such as 18‐acetoxy‐4‐hydroxydictyo‐19‐al (7). Molecular‐mechanics calculations suggest that typical‐xenicane cis‐conformers are disfavoured by mainly C(4)–C(5) torsional strain. This is confirmed by the observation of two sizably populated cis‐and trans‐conformers for the unnatural 4‐oxoxenicanes 10–12. Unusually facile thermal (E)→(Z) isomerization of xenicanes 1,3,10–12, and 7 is also observed (→ 13–17 and 9, resp.; Scheme 3), reflecting great strain relief in the transition state. Conflicting results in the literature now fit into this scheme which provides a basis for unravelling recognition phenomena with these biologically active systems.

New xenicane diterpenes from the brown algae of dictyotaceae

Two new xenicane diterpenes have been isolated from the brown algae of the Dictyotaceae family, and their structures and absolute configurations have been elucidated on the basis of their spectral and X-ray diffraction analyses.