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Marine-Derived Leads as Anticancer Candidates by Disrupting Hypoxic Signaling through Hypoxia-Inducible Factors
Maria Rita Garcia1,2,3, Paula B Andrade1, Florence Lefranc4
1REQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, 4050-313 Porto, Portugal.
Abstract:
The inadequate vascularization seen in fast-growing solid tumors gives rise to hypoxic areas, fostering specific changes in gene expression that bolster tumor cell survival and metastasis, ultimately leading to unfavorable clinical prognoses across different cancer types. Hypoxia-inducible factors (HIF-1 and HIF-2) emerge as druggable pivotal players orchestrating tumor metastasis and angiogenesis, thus positioning them as prime targets for cancer treatment. A range of HIF inhibitors, notably natural compounds originating from marine organisms, exhibit encouraging anticancer properties, underscoring their significance as promising therapeutic options. Bioprospection of the marine environment is now a well-settled approach to the discovery and development of anticancer agents that might have their medicinal chemistry developed into clinical candidates. However, despite the massive increase in the number of marine natural products classified as 'anticancer leads,' most of which correspond to general cytotoxic agents, and only a few have been characterized regarding their molecular targets and mechanisms of action. The current review presents a critical analysis of inhibitors of HIF-1 and HIF-2 and hypoxia-selective compounds that have been sourced from marine organisms and that might act as new chemotherapeutic candidates or serve as templates for the development of structurally similar derivatives with improved anticancer efficacy.
Insights
Marine natural products show promise as anticancer agents by inhibiting hypoxia-inducible factors (HIF-1 and HIF-2), which drive tumor growth and metastasis. Further research into these compounds could lead to novel cancer therapies.
Area of Science:
- Marine natural products
- Medicinal chemistry
- Cancer biology
Background:
- Tumor hypoxia promotes cancer cell survival and metastasis, leading to poor clinical outcomes.
- Hypoxia-inducible factors (HIF-1 and HIF-2) are key regulators of tumor angiogenesis and metastasis, making them attractive therapeutic targets.
- Marine organisms are a rich source of natural products with potential anticancer properties.
Purpose of the Study:
- To critically analyze marine-derived inhibitors of HIF-1 and HIF-2.
- To explore hypoxia-selective compounds from marine sources as potential anticancer agents.
- To identify marine natural products that can serve as templates for developing improved cancer therapeutics.
Main Methods:
- Literature review of marine natural products targeting HIF pathways.
- Analysis of anticancer properties and molecular mechanisms of marine compounds.
- Assessment of therapeutic potential for cancer treatment.
Main Results:
- Marine natural products, particularly HIF inhibitors, demonstrate significant anticancer potential.
- Several marine compounds exhibit promising activity against tumor hypoxia and associated processes.
- While many marine natural products show general cytotoxicity, few are characterized for specific molecular targets.
Conclusions:
- Marine natural products offer a valuable resource for discovering novel HIF inhibitors and hypoxia-selective anticancer agents.
- Further investigation into the molecular mechanisms of these compounds is crucial for drug development.
- Marine-derived compounds can serve as lead structures for developing next-generation cancer chemotherapeutics.
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