The marine sponge metabolite mycothiazole: A novel prototype mitochondrial complex I inhibitor

Morgan, Jody; Mahdi, Fakhri; Liu, Yang; Coothankandaswamy, Veena; Jekabsons, Mika B.; Johnson, Tyler A.; Sashidhara, Koneni V.; Crews, Phillip; Nagle, Dale G.; Zhou, Yifeng

doi:10.1016/j.bmc.2010.06.072

Cited by 50 publications

(60 citation statements)

References 23 publications

(32 reference statements)

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“…3.3), a metabolite isolated from a Petrosaspongia mycofijiensis sponge, inhibited hypoxic HIF-1 signaling in tumor cells in the nanomolar range, what correlated with the suppression of hypoxia-stimulated VEGF secretion by tumor and angiogenesis in vitro. Nevertheless, the high neurotoxicity of this compound, that selectively suppresses the mitochondrial respiration at complex I (NADH-ubiquinone oxidoreductase) prevents its use as an anticancer drug [82].…”

Section: Compounds That Inhibit the Activation Of The Angiogenic Switchmentioning

confidence: 99%

Marine Sponge Derived Antiangiogenic Compounds

Quesada

Martínez‐Poveda

Rodriguez-Nieto³

et al. 2014

Handbook of Anticancer Drugs From Marine Origin

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Angiogenesis plays an essential role in tumor growth, invasion, and metastasis. Inhibition of angiogenesis has become a major challenge in the development of new anticancer agents, with a countless number of antiangiogenic strategies being tested in preclinical and clinical trials. Nowadays the clinical development of antiangiogenic therapies seems to be unstoppable, not only for cancer, but also for an increasing number of non-neoplasic angiogenesis-related diseases. Although most of the natural compounds previously described as inhibitors of angiogenesis have been isolated from plants and terrestrial microorganisms, increasing attention is being paid to the development of marine-derived antiangiogenic agents. Marine organisms produce interesting and singular pharmacological lead compounds, derived from the large diversity of marine habitats and environmental conditions. Among the many different types of marine organisms used as a source for drug discovery, sponges represent one of the most promising sources of leads in the research of new cancer drugs. There are different strategies for angiogenesis intervention, based on the modulation of any of the different steps of the angiogenic process. In this chapter, we will provide an overview of the angiogenesis inhibitors isolated from marine sponges based on the available information regarding their primary targets or mechanism of action.

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Section: Compounds That Inhibit the Activation Of The Angiogenic Switchmentioning

confidence: 99%

Marine Sponge Derived Antiangiogenic Compounds

Quesada

Martínez‐Poveda

Rodriguez-Nieto³

et al. 2014

Handbook of Anticancer Drugs From Marine Origin

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“…Mechanistic studies revealed that mycothiazole selectively suppresses mitochondrial respiration at complex I (NADH-ubiquinone oxidoreductase), may serve as a valuable molecular probe for mitochondrial biology and HIF-mediated hypoxic signaling [90]. …”

Section: Peptides That Inhibit Angiogenesismentioning

confidence: 99%

Antitumor Peptides from Marine Organisms

et al. 2011

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The biodiversity of the marine environment and the associated chemical diversity constitute a practically unlimited resource of new antitumor agents in the field of the development of marine bioactive substances. In this review, the progress on studies of antitumor peptides from marine sources is provided. The biological properties and mechanisms of action of different marine peptides are described; information about their molecular diversity is also presented. Novel peptides that induce apoptosis signal pathway, affect the tubulin-microtubule equilibrium and inhibit angiogenesis are presented in association with their pharmacological properties. It is intended to provide useful information for further research in the fields of marine antitumor peptides.

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“…[1] It exhibits toxicity towards lung cancer cells [2] and very recently was proven to be a valuable novel prototype of mitochondrial complex I inhibitor. [3] Its unique structure as well as its potential pharmacological activities make it a good target for laboratories interested in the total synthesis of biologically active natural compounds. There are only two total syntheses of mycothiazole (1) [2,4] and three partial syntheses published so far [5] but these lead to the wrong stereochemistry at the C14-C15 double bond, which was first claimed to be E and finally revised to Z.…”

Section: Introductionmentioning

confidence: 99%

Towards the Synthesis of the 4,19‐Diol Derivative of (–)‐Mycothiazole: Synthesis of a Potential Key Intermediate

Batt

Fache

2011

Eur J Org Chem

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The synthesis of a potential key intermediate for the synthesis of the 4,19‐diol derivative of (–)‐mycothiazole using convergent strategies is described in this paper. Several approaches have been tested, including cross metathesis and a Julia–Kocienski olefination. Finally, the formation of the 1,1‐dialkyl‐1,2‐ethanediol motif through C4–C5 bond construction was realized by nucleophilic addition of a vinyl iodide derivative to a keto ester after halogen/lithium exchange followed by reduction of the resulting hydroxy ester.

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The marine sponge metabolite mycothiazole: A novel prototype mitochondrial complex I inhibitor

Cited by 50 publications

References 23 publications

Marine Sponge Derived Antiangiogenic Compounds

Marine Sponge Derived Antiangiogenic Compounds

Antitumor Peptides from Marine Organisms

Towards the Synthesis of the 4,19‐Diol Derivative of (–)‐Mycothiazole: Synthesis of a Potential Key Intermediate

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