Tshuva Research Group

Synthetic Bioinorganic Chemistry

Research at the Tshuva laboratory includes the design, preparation, and characterization of transition metal coordination complexes for the investigation of biological or medicinal questions. The laboratory combines synthetic organic and inorganic chemistry with biochemical investigations to evaluate the bioactivity of the compounds developed.

Development of advanced metal-based anticancer chemotherapy is one of the leading lines of research in our laboratory. Chemotherapy is normally extremely aggressive toward cancer cells, with limited selectivity causing severe side effect. One example is cisplatin, highly effective yet leading to substantial liver, kidneys, and brain damages. Unlike the toxic Pt ion, the labile Ti metal is bio-friendly, and Ti(IV) complexes of organic ligands hydrolyze in biological environments to titanium dioxide – a known safe material with no side effects. In fact, the hydrolysis is generally so rapid as to inhibit possible use of such complexes in biology.

We develop hydrolytically stable defined complexes that can inflect controlled bioactivity prior to decomposition to a safe final product. Our lead compounds show high efficacy against a wide variety of tumor types (both in vitro and in vivo), thus fat without any detected side effects (on mice). Mechanistic analyses point to a distinct mechanism, which appears to involve ER-stress and hypoxia. Research in this area focuses on custom-design of modern compounds with or without combination with other bioactive agents, profound mechanistic analyses, and development of targeting platforms.

Selected Publications

• Sigalit Meker, Ori Braitbard, Matthew D. Hall, Jacob Hochman, and Edit Y. Tshuva. Specific Design of Titanium(IV) Phenolato Chelates Yields Stable and Accessible, Effective and Selective Anticancer Agents. Chem. Eur. J. (2016, 22, 9986)
• Michal S. Shoshan and Edit Y. Tshuva. Effective Inhibitors of ROS Cellular Production by MXCXXC-Type Peptides: Potential Therapeutic Applications in Copper Homeostasis Disorders. Chem. Eur. J. (2016, 22, 9077)
• Nitzan Ganot and Edit Y. Tshuva. In vitro combinations of inert phenolato Ti(IV) complexes with clinically employed anticancer chemotherapy: synergy with oxaliplatin on colon cells. RSC Adv. (2018, 8, 5822)
• Avia Tzubery, Naomu Melamed-Book, and Edit Y. Tshuva. Fluorescent antitumor titanium(iv) salen complexes for cell imaging. Dalton Trans. (2018, 47, 3669)
• Nitzan Ganot, Ori Braitbard, Asaad Gammal, Joseph Tam, Jacob Hochman, and Edit Y. Tshuva. In Vivo Anticancer Activity of a Nontoxic Inert Phenolato Titanium Complex: High Efficacy on Solid Tumors Alone and Combined with Platinum Drugs. ChemMedChem (2018, 13, 2290)
• Gilad Nahari, Ori Braitbard, Liraz Larush, Jacob Hochman, and Edit Y. Tshuva. Effective Oral Administration of an Antitumorigenic Nanoformulated Titanium Complex. ChemMedChem (2020, 15, 00)
• Maya Miller, Anna Mellul, Maya Braun, Dana Sherill-Rofe, Emiliano Cohen, Zohar Shpilt, Irene Unterman, Ori Braitbard, Jacob Hochman, Edit Y. Tshuva, and Yuval Tabach. Titanium Tackles the Endoplasmic Reticulum: A First Genomic Study on a Titanium Anticancer Metallodrug. iScience (2020, 23, 10262)

For the full publications list, visit Prof. Tshuva's ORCID page.