Tuning of organic ligands in metal complexes for anticancer activity and selective delivery

Abstract

1. Introduction Metal ions, combined with organic and inorganic ligands provide an excellent opportunity to deal with various aspects of diagnosis and treatment of different diseases with a multitude of tasks. [1] With the luxury of choosing from tens of metal ions and thousands of ligand systems, coordination and organometallic chemists can explore the possibilities to hit the right combination to come up with new molecules for extensive medical applications. Among various medical challenges, cancer remains the leading cause of death worldwide, with over ten million cases in a calendar year. [2] The utilization of metallodrugs against cancer has started to be investigated in a modern scientific way with the discovery of cisplatin, which has been found to be cytotoxic in nature. [3] With the success of cisplatin in cancer treatment in the seventies, various other platinum-based compounds have been tested as prospective anticancer agents, and among them, carboplatin, oxaliplatin, nedaplatin, lobaplatin, and heptaplatin have been approved by different drug controlling agencies for cancer treatment. [4] This group of metallodrugs can work efficiently against testicular, cervical, ovarian, head and neck and non-small cell lung cancer. [5] Nevertheless, certain limitations restrict their extensive use in the treatment. Among them, poor selectivity of the drugs towards cancer -specific cells complicates the treatment with unavoidable side effects, and increasing chemoresistance remains another major concern. [6] Therefore, there is an urgency to look beyond platinum for alternative improved metallodrugs with better efficiency, reduced side effects and lesser chemoresistance. As an alternative option new metal ion(s) with the ability of different mechanistic pathways and toxicity profiles started to get investigated with time. Among various metal ions, ruthenium has been found to be very much effective with several advantages that can be exploited to prepare better anticancer metallodrugs. [7] Ruthenium, with its preference for hexa-coordinated geometry, provides ample opportunity to load the coordination sphere with various bioactive ligands.