Decoding the prospective of metal complexes in anti-cancer therapeutics by targeting of G-quadruplex DNA

Abstract

The use of metallodrugs in cancer therapy received widespread interest after the successful application of cisplatin and its analogous compounds as chemotherapeutic medications. Despite the development of various metallodrugs in past years, platinum-based chemotherapeutic agents are the only clinically approved metallodrugs that primarily interact with genomic DNA and trigger severe dose-limiting adverse side effects in cancer patients. As a consequence, the advancement of new risk-free metallodrugs has become a topmost concern in cancer research to minimize toxicity and improve therapeutic outcomes. G-quadruplex (G4) DNA structures have recently come to light as an attractive drug target in cancer therapy because of their gene regulation ability and role in maintaining genomic stability. Their presence in telomere and promoter region of oncogenes has the potential to induce apoptosis in cancer cells through the inhibition of telomerase activity and gene expression. Therefore, the development of new G4 DNA targeting small molecular entities including metal complexes came out as a viable approach for uprooting cancer disease. Beyond organic small molecules, innumerable metal complexes have been developed in past years to target G4 DNA structures in the context of cancer therapy. This review primarily aims to highlight these metal complexes through a comprehensive discussion about their structural properties, their binding interactions with G4 DNA, their cancer cell growth inhibition mechanisms, and their efficacy in both cellular and in vivo systems, to decode their potential as anti-cancer drugs. Additionally, the potential of these metal complexes in the field of bio-imaging and photodynamic therapy is also explored.