Recent advances in Rh(III)-based anticancer complexes

Abstract

Since the serendipitous discovery of cisplatin's anticancer activity, transition metal complexes have caught enormous attention in medicinal inorganic chemistry, especially in cancer drug development research. Recently, the drug resistance and side effect problems of market-available cancer drugs have accelerated the screening of novel transition metal complexes in cancer therapy. Over the past few years, Rh(III)-based complexes have received significant attention from inorganic chemists as possible alternatives to Pt(II) anticancer drugs. Numerous Rh(III) complexes are reported to be more cytotoxic and effective than cisplatin against various cancer types. Interestingly, several Rh(III) complexes have shown remarkable anticancer efficacy even against cisplatin-resistant cancer cells, making them potential solutions for drug resistance problems. The anticancer efficacy of such Rh(III) complexes was super-tuned by the rational selection of ligands and overall charge. Moreover, these anticancer active complexes also exhibited different novel anticancer mechanisms by targeting specific biomolecules/organelles to overcome drug resistance. In this review, we discussed smartly designed Rh(III) complexes that presented efficient antiproliferative activity via different mechanisms of action (MoA) from conventional chemotherapeutics (such as cisplatin). Herein we have focused on their MoA such as targeting specific organelle (mitochondria) and mismatched DNA base pair, selective inhibition of protein or enzyme (thioredoxin reductase), delivery of bioactive ligands (curcumin) at the tumor site by cytotoxic Rh(III) complexes. Apart from this, we have also discussed the in-solution behavior of Rh(III) complexes, their stability in a different medium, and their ability to provide live cell or organelle imaging used to track the cellular co-localization of drugs. © 2024 Elsevier B.V.