Exploring Metallodrugs in Cancer Therapy

Suman Adhikari^1*Morteza Montazerozohori²ANJOY MAJHI³Surajit Pathak⁴

• ¹Govt. Degree College, Dharmanagar, Tripura, India, Dharamanagar, India
• ²Yasouj University, Yasuj, Iran
• ³Presidency University Kolkata, Kolkata, India
• ⁴Chettinad Hospital and Research Institute, Kanchipuram, India

Following cisplatin's success in the treatment of cancer, numerous other platinum-based complexes have been investigated as potential anticancer drugs, and some of these have received regulatory approval for purpose of treating cancer. Despite the fact that platinumbased metallodrugs are effective against many different forms of cancer, their widespread usage in treatment is constrained by a number of factors (chemoresistance, poor selectivity, inherent toxicities, etc.) (Romani 2022). To address the unresolved clinical issues associated with platinum-based metallodrugs, many researchers are focusing on the design and synthesis of metallodrugs with improved biological activity and selectivity, reduced toxicity and alternative mechanisms of action compared to those of platinum-based compounds. Several strategies have been explored to enhance the effectiveness and reduce the adverse effects of metallodrugs. These include the use of various transition metal-based complexes with bioactive ligands that introduce new modes of action, improve delivery, permit selective activation, provide synergistic effects, and enhance tumour accumulation. Metal complexes of ruthenium, gold, copper, iridium, and osmium have been evaluated against various cancer cell lines and are regarded as promising alternatives to Platinum-based drugs, thereby driving substantial interest in the development of new anticancer drugs (Adhikari et al. 2024). The scientific community currently faces a significant challenge in developing potent anticancer therapeutics with high selectivity and minimal toxicity. Owing to their distinctive properties of metals, such as their redox activity, diverse coordination modes, and reactivity towards biomolecules, metal complexes have attracted considerable attention for their therapeutic potential in cancer therapy. These characteristics have made metal complexes desirable candidates for targeting biomolecular targets with specificity, thereby modulating cellularproliferation mechanisms.The goal of this Research Topic is to give readers a broad overview of recently produced metallodrugs used in cancer treatment, with a focus on their past, current, and potential future applications.This special issue, "Metallodrugs in cancer therapy" compiles five articles on the latest advances in areas of metal-based complexes for the treatment of cancer.Mitochondria plays an important role in tumor biology, regulating cellular energy metabolism, free radical generation, apoptosis, autophagy, signal transmission, and other essential biological processes (Nath et al. 2024). The review work of Zheng and co-workers has been focused on the thiosemicarbazone-based metal complexes for cancer therapy through the mitochondrial signalling pathway (Zheng et al. 2024). This review highlights the design and synthesis of various thiosemicarbazone-based metal complexes and their role in anticancer studies. The authors discussed the structure-activity relationship of thiosemicarbazone scaffolds and highlighted the effects of various substituents attached to thiourea, as well as the role of different metal ions in modulating anticancer activity. The authors attributed that the thiosemicarbazone-based metal complexes have the ability to pass through cell membranes and accumulate in the inner mitochondrial membrane, where they reduce mitochondrial membrane potential and induce apoptosis. (Moynihan et al. 2024). These Pt(IV) complexes exhibited strong activity against several cancer cell lines, including glioblastoma (U87), osteosarcoma (U2-OS, SOAS-2, and MG63), and breast cancer (MDAMB 468). Furthermore, Pt(IV) complex drug uptake in 3D