Callipeltin A, a Cyclic Depsipeptide Inhibitor of the Cardiac Sodium–Calcium Exchanger and Positive Inotropic Agent

Trevisi, Lucia; Bova, Sergio; Cargnelli, Gabriella; Danieli-Betto, Daniela; Floreani, Maura; Germinario, Elena; D’Auria, Maria Valeria; Luciani, Sisto

doi:10.1006/bbrc.2000.3906

Cited by 30 publications

(19 citation statements)

References 11 publications

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“…Callipeltin A is a macrocyclic lactone containing four amino acids in the L configuration, alanine, leucine, threonine (two residues); one (arginine) in the D configuration; two N -methyl amino acids, N -methyl alanine and N -methyl glutamine; a methoxy tyrosine, a 3,4-dimethyl- l -glutamine; and a 4-amino-7-guanidino-2,3-dihydroxypentanoic acid (AGDHE), formally derived from l -arginine [70]. …”

Section: Compounds With Anti-tumor Activitymentioning

confidence: 99%

Cyclodepsipeptides from Marine Sponges: Natural Agents for Drug Research

2010

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A number of natural products from marine sponges, such as cyclodepsipeptides, have been identified. The structural characteristics of this family of cyclic peptides include various unusual amino acid residues and unique N-terminal polyketide-derived moieties. Papuamides are representatives of a class of marine sponge derived cyclic depsipeptides, including callipeltin A, celebesides A and B, homophymine A, mirabamides, microspinosamide, neamphamide A and theopapuamides. They are thought to have cytoprotective activity against HIV-1 in vitro by inhibiting viral entry. Jasplakinolide, a representative member of marine sponge-derived cyclodepsipeptides that include arenastatin A, geodiamolides, homophymines, spongidepsin and theopapuamides, is a potent inducer of actin polymerization in vitro. Although actin dynamics is essential for tumor metasasis, no actin targeting drugs have been used in clinical trials due to their severe cytotoxicity. Nonetheless, the actin cytoskeleton remains a potential target for anti-cancer drug development. These features imply the use of cyclodepsipeptides as molecular models in drug research.

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Section: Compounds With Anti-tumor Activitymentioning

confidence: 99%

Cyclodepsipeptides from Marine Sponges: Natural Agents for Drug Research

2010

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“…Supporting Information (see footnote on the first page of this article): Table S1 reports the two sets of calculated J-values of erythro and threo forms of AGDHE 2,3 obtained varying centre C-4, compared to the experimental data. Moreover, Table S1 contains the two sets of calculations performed on the erythro and threo forms of AGDHE 3,4 , this time varying C-2.…”

Section: Nmr Experimentsmentioning

confidence: 99%

“…Since the two sets of calculations pointed to the same results, and on the basis of the results of the calculation regarding AGDHE 3,4 we reported, for sake of simplicity, only the results of the set of calculations containing the correct relative configuration of C-4. Same considerations apply for fragment AGDHE 3,4 , this time varying C-2. Also in this case, we reported only the set of calculations containing the correct configuration of C-2.…”

Section: Introductionmentioning

confidence: 99%

“…More recently, callipeltin A was found to be a selective and powerful inhibitor of the cardiac sodium/calcium exchanger and eliciting interest as a potential regulator of myocardial contractility. [4] Callipeltin A (1) is the first member of a growing group of potent antiviral marine peptides, which comprises papuamides A-C, [5] microspinamide, [6] and neamphamide, [7] and with which it shares a certain degree of structural homology, suggesting in turn a potential common pharmacophore.…”

Section: Introductionmentioning

confidence: 99%

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Quantum Mechanical Calculation of Coupling Constants in the Configurational Analysis of Flexible Systems: Determination of the Configuration of Callipeltin A

et al. 2006

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“…For example, there is a report which showed the preparation of a series of macrocyclic polyethers with inotropic activity [1]. Other data indicate that macrocyclic callipeltin exerts a positive inotropic effect in the left atria from the hearts of guinea pigs [2]. In addition, a study showed that a series of macrocyclic polyamines can induce a positive inotropic effect in atrial cells of dog [3].…”

Section: Introductionmentioning

confidence: 99%

Design and synthesis of a new steroid-macrocyclic derivative with biological activity

et al. 2017

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The aims of this study were to evaluate the positive inotropic effect of a new macrocyclic derivative (compound 11) and characterize the molecular mechanism involved in its biological activity. The first step was achieved by synthesis of a macrocyclic derivative involving a series of reactions for the preparation of several steroid derivatives such as (a) steroidpyrimidinone (3 and 4), (b) steroid-amino (5), (c) steroidimino (6), (d) ester-steroid (7 and 8), and (e) amido-steroid (9 and 10). Finally, 11 was prepared by removing the tertbutyldimethylsilane fragment of 10. The biological activity of compounds on perfusion pressure and vascular resistance was evaluated on isolated rat heart using the Langendorff model. The inotropic activity of 11 was evaluated in presence of prazosin, metoprolol, indomethacin, nifedipine, and flutamide to characterize its molecular mechanism. Theoretical experiments were carried out with a Docking model, to assess potential interactions of androgen receptor with 11. The results showed that only this macrocyclic derivative exerts changes on perfusion pressure and vascular resistance translated as the positive inotropic effect, and this effect was blocked with flutamide; these data indicate that the positive inotropic activity induced by this macrocyclic derivative was via androgen receptor activation. The theoretical results indicated that the interaction of the macrocyclic derivative with the androgen receptor involves several amino acid residues such as Leu 704 , Asn 705 , Met 780 , Cys 784 , Met 749 , Leu 762 , Phe 764 , Ser 778 , and Met 787 . In conclusion, all these data suggest that the positive inotropic activity of the macrocyclic derivative may depend on its chemical structure.

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Callipeltin A, a Cyclic Depsipeptide Inhibitor of the Cardiac Sodium–Calcium Exchanger and Positive Inotropic Agent

Cited by 30 publications

References 11 publications

Cyclodepsipeptides from Marine Sponges: Natural Agents for Drug Research

Cyclodepsipeptides from Marine Sponges: Natural Agents for Drug Research

Quantum Mechanical Calculation of Coupling Constants in the Configurational Analysis of Flexible Systems: Determination of the Configuration of Callipeltin A

Design and synthesis of a new steroid-macrocyclic derivative with biological activity

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