Marine-Derived Pharmaceuticals - Challenges and Opportunities

Lindequist, Ulrike

doi:10.4062/biomolther.2016.181

Cited by 180 publications

(114 citation statements)

References 82 publications

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“…While this has the potential to speed up protein production, it is limited as targeting across the cytoplasmic membrane can substantially limit periplasmic yields [166,167]. Marine non-peptidyl compounds also pose challenges inherent to their chemistry and organisms that produce them [168]. However, once production of marine compounds is achieved, their stability, formulation, delivery, and antigenicity need to be overcome.…”

Section: Challenges and Outlookmentioning

confidence: 99%

Marine Toxins Targeting Kv1 Channels: Pharmacological Tools and Therapeutic Scaffolds

et al. 2020

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Toxins from marine animals provide molecular tools for the study of many ion channels, including mammalian voltage-gated potassium channels of the Kv1 family. Selectivity profiling and molecular investigation of these toxins have contributed to the development of novel drug leads with therapeutic potential for the treatment of ion channel-related diseases or channelopathies. Here, we review specific peptide and small-molecule marine toxins modulating Kv1 channels and thus cover recent findings of bioactives found in the venoms of marine Gastropod (cone snails), Cnidarian (sea anemones), and small compounds from cyanobacteria. Furthermore, we discuss pivotal advancements at exploiting the interaction of κM-conotoxin RIIIJ and heteromeric Kv1.1/1.2 channels as prevalent neuronal Kv complex. RIIIJ’s exquisite Kv1 subtype selectivity underpins a novel and facile functional classification of large-diameter dorsal root ganglion neurons. The vast potential of marine toxins warrants further collaborative efforts and high-throughput approaches aimed at the discovery and profiling of Kv1-targeted bioactives, which will greatly accelerate the development of a thorough molecular toolbox and much-needed therapeutics.

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Section: Challenges and Outlookmentioning

confidence: 99%

Marine Toxins Targeting Kv1 Channels: Pharmacological Tools and Therapeutic Scaffolds

et al. 2020

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“…Marine-derived compounds provide many of the lead structures used as templates for the generation of novel molecules with enhanced biological activity. Several of these compounds are already being used for the treatment of different pathological conditions, including cancer, viral and fungal infections, inflammatory diseases, and thrombosis [21]. The latter is mainly controlled by phospho-regulated signaling transductions, such as the PI3K pathway.…”

Section: Discussionmentioning

confidence: 99%

The Marine-Derived Triterpenoid Frondoside A Inhibits Thrombus Formation

et al. 2020

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Background:The marine-derived triterpenoid frondoside A inhibits the phosphatidylinositol-3-kinase (PI3K) pathway in cancer cells. Because this pathway is also crucially involved in platelet activation, we studied the effect of frondoside A on thrombus formation. Methods: Frondoside A effects on platelet viability, surface adhesion molecule expression, and intracellular signaling were analyzed by flow cytometry and Western blot. The effect of frondoside A was analyzed by photochemically induced thrombus formation in the mouse dorsal skinfold chamber model and by tail vein bleeding. Results: Concentrations of up to 15 µM frondoside A did not affect the viability of platelets, but reduced their surface expression of P-selectin (CD62P) and the activation of glycoprotein (GP)IIb/IIIa after agonist stimulation. Additional mechanistic analyses revealed that this was mediated by downregulation of PI3K-dependent Akt and extracellular-stimuli-responsive kinase (ERK) phosphorylation. Frondoside A significantly prolonged the complete vessel occlusion time in the mouse dorsal skinfold chamber model of photochemically induced thrombus formation and also the tail vein bleeding time when compared to vehicle-treated controls. Conclusion: Our findings demonstrated that frondoside A inhibits agonist-induced CD62P expression and activation of GPIIb/IIIa. Moreover, frondoside A suppresses thrombus formation. Therefore, this marine-derived triterpenoid may serve as a lead compound for the development of novel antithrombotic drugs.

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“…Brentuximab vedotin was approved for the treatment of Hodgkin's lymphoma and anaplastic large T-cell malignant lymphoma, cytarabine for leukemia, trabectedin for ovarian cancer and soft tissue sarcoma, eribulin mesylate for metastatic breast cancer, Ziconotide for pain, omega-3-acid ethyl esters for hypertriglyceridemia, vidarabine for recurrent epithelial keratitis caused by HSV, superficial keratitis and acute kerato-conjunctivitis; many other compounds are undergoing clinical trials. 47,[52][53][54][55][56] Clinical trials involving cephalostatins 1 and 7 have been hindered because of the complications in harvesting the materials (0.1 g and <60 mg of cephalostatins 1 and 7, respectively, from 450 kg of the marine tube worm (Cephalodiscus gilchristi) from 60 to 80 m deep in sea waters near East Africa. 57 Synthesis of cephalostatin will render the bis-steroidal alkaloid more available and allow clinical trials.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic value of steroidal alkaloids in cancer: Current trends and future perspectives

Dey

Kundu

Chakraborty

et al. 2019

Intl Journal of Cancer

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Discovery and development of new potentially selective anticancer agents are necessary to prevent a global cancer health crisis. Currently, alternative medicinal agents derived from plants have been extensively investigated to develop anticancer drugs with fewer adverse effects. Among them, steroidal alkaloids are conventional secondary metabolites that comprise an important class of natural products found in plants, marine organisms and invertebrates, and constitute a judicious choice as potential anti‐cancer leads. Traditional medicine and modern science have shown that representatives from this compound group possess potential antimicrobial, analgesic, anticancer and anti‐inflammatory effects. Therefore, systematic and recapitulated information about the bioactivity of these compounds, with special emphasis on the molecular or cellular mechanisms, is of high interest. In this review, we methodically discuss the in vitro and in vivo potential of the anticancer activity of natural steroidal alkaloids and their synthetic and semi‐synthetic derivatives. This review focuses on cumulative and comprehensive molecular mechanisms, which will help researchers understand the molecular pathways involving steroid alkaloids to generate a selective and safe new lead compound with improved therapeutic applications for cancer prevention and therapy. In vitro and in vivo studies provide evidence about the promising therapeutic potential of steroidal alkaloids in various cancer cell lines, but advanced pharmacokinetic and clinical experiments are required to develop more selective and safe drugs for cancer treatment.

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Marine-Derived Pharmaceuticals - Challenges and Opportunities

Cited by 180 publications

References 82 publications

Marine Toxins Targeting Kv1 Channels: Pharmacological Tools and Therapeutic Scaffolds

Marine Toxins Targeting Kv1 Channels: Pharmacological Tools and Therapeutic Scaffolds

The Marine-Derived Triterpenoid Frondoside A Inhibits Thrombus Formation

Therapeutic value of steroidal alkaloids in cancer: Current trends and future perspectives

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