 Contel, Maria |
Academic Appointments: Professor, Chemistry Department, Brooklyn College, The City University of New York Degree(s) Ph.D. (Chemistry) Public University of Navarra, Spain Research Focus: My research program focuses on the synthesis and characterization of transition-metal complexes (early and late transition metals such as gold, silver, copper, platinum, palladium, ruthenium and titanium) and their applications as: a) anticancer and antimicrobial agents and b) as catalysts in reactions of industrial interest (including but not limited to oxidations and C-C and C-Heteroatom bond formation). In the cancer field, the long-term goal of my research is the development of novel metal-based chemotherapeutics for different diseases that can overcome some of the drawbacks associated with the use of existing drugs. My group has focused on the synthesis of new potential anticancer agents based on gold, platinum, palladium and ruthenium and iminophosphorane ligands endowed with promising activities displaying a mode of action different to that of the most commonly used metallodrug: cisplatin. Recently, we have unveiled the potential of a water-soluble ruthenium compound as a breast cancer chemotherapeutic which shows an impressive tumor reduction size in vivo in mice (xenograft model). We have also focused on the preparation of heterometallic gold complexes as anticancer agents. Our hypothesis is that the incorporation of two different metals with anti-tumor properties in the same molecule will improve their activity due to: a) interaction of the different metals with multiple biological targets and b) improved chemicophysical properties of the resulting heterometallic compound. In this context, we have reported that such an approach is a feasible one and that new titanium- and ruthenium-gold complexes may be promising candidates with improved antitumor properties with respect to their monometallic (titanium, ruthenium and gold) precursors in renal cancer (with impressive tumor reduction size in vitro in xenograft models in mice, displaying anti-migratory properties and, in some case anti-angiogenic properties). More recently, we are working on more targeted therapies by improving the delivery of some of these and other metal-based cytotoxic agents by: a) using enzyme-cleavable biodegradable nanocarriers, and, b) using monoclonal antibodies to generate potent antibody-drug conjugates that are specific to certain cancerous tumors. Selected Publications Elie B, Hubbard K, Layek B, Seok Yang W, Prabha S, Ramos J, Contel M. (2020) Auranofin-Based Analogues Are Effective Against Clear Cell Renal Carcinoma In Vivo and Display No Significant Systemic Toxicity. ACS Pharmacol. Transl. Sci. https://doi.org/10.1021/acsptsci.9b00107 Del Solar V, Contel M. (2019). Metal-Based Antibody Drug Conjugates. Potential and Challenges in Their Application as Targeted Therapies in Cancer. J Inorg Biochem; https://doi.org/10.1016/j.jinorgbio.2019.110780. Elie BT, Hubbard K, Pechhenyy Y, Layek B, Prabha S, Contel M. (2019). Preclinical Evaluation of an Unconventional Ruthenium-Gold-Based Chemotherapeutic: RANCE-1, in Clear Cell Renal Cell Carcinoma. Cancer Med; 4304 https://doi.org/10.1002/cam4.2322 (open access). Curado N, Dewaele-Le Roi G, Poty S, Lewis JS, Contel M. (2019). Trastuzumab gold-conjugates: synthetic approach and in vitro evaluation of anticancer activities in breast cancer cell lines. Chem. Commun; 55, 1394. DOI: 10.1039/c8cc08769e. Curado, N, Contel M. Heterometallic Complexes as Anticancer Agents In: Metal-based Anticancer Agents (Series Metallobiology). (A, Casini, S. Meier-Menches, A. Vessieres Eds.), Royal Society of Chemistry. 2019. https://pubs.rsc.org/en/content/chapter/bk9781788014069-00143/978-1-78801-406-9. Patents Contel M, Marzo I, Frik M, Elie BT. Arene ruthenium (II) derivatives containing iminophosphorane ligands and their use in cancer therapy. US Patent 9,555,049 B2 (01/31/2017). Contel M, Fernández-Gallardo J, Elie BT, Ramos JW. Titanocene Gold Derivatives Comprising Thiolato Ligands. US Patent 9,315,531 (04/19/2016). Grants over the last 5 years Contel, PI Contel, PI
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