Structural modifications on CORM-3 lead to enhanced anti-angiogenic properties against triple-negative breast cancer cells.

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ID: 85611
2019
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Abstract
Carbon monoxide-releasing molecules (CORMs) are a special class of organometallic complexes that have been reported to offer beneficial effects against different conditions including several subtypes of cancer. Especially for the aggressive and poorly treated triple-negative breast cancer (TNBC), early CORMs have been shown to diminish malignant angiogenesis and may be considered as an alternative approach. So, this study aimed at testing novel CORM molecules against angiogenesis in TNBC seeking potent drug candidates for new therapies.Based on previous studies, CORM-3 was chosen as the lead compound and a group of 15 new ruthenium-based CORMs were synthesized and subsequently evaluated in vitro for potential anti-angiogenic properties.A similar anti-angiogenic behaviour to the lead complex was observed and a new CORM, complex 4, emerged as a promising agent from this study. Specifically, this complex offered better inhibition of the activation of VEGFR2 and other downstream proteins of vascular endothelial cells. Complex 4 also retained the ability of the parent molecule to reduce the upregulated VEGF expression from TNBC cells and inhibit endothelial cell migration and new vessel formation. The lack of significant cytotoxicity and the downregulating activity over the cytoprotective enzyme haem oxygenase-1 (HO-1) in cancer cells may also favour CORMs against this poorly treated subtype of breast cancer.Since the anti-angiogenic approach is one of the few available targeted strategies against TNBC, both CORM-3 and the new complex 4 should be considered for further research as combination agents with existing anti-angiogenic drugs for a more effective treatment of malignant angiogenesis in TNBC.
Reference Key
kourti2019structuralmedicinal Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Kourti, Malamati;Cai, Jun;Jiang, Wen;Westwell, Andrew D;
Journal medicinal chemistry (shariqah (united arab emirates))
Year 2019
DOI
10.2174/1573406415666191206102452
URL
Keywords
Breast cancer angiogenesis anti-angiogenic therapy corm-3 carbon-monoxide releasing molecules (corms) triple-negative breast cancer (tnbc)

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