Organotin(IV) Azo Hydrazonates as Lysosome-Targeted Anticancer Agents

Abstract

Following the success of cisplatin, several platinum-based anti-cancer metallodrugs were discovered, including carboplatin, oxaliplatin, and nedoplatin. Nevertheless, the severe adverse side effects associated with these Pt-based drugs have limited their widespread clinical use and prompted the hunt for non-Pt-based medication alternatives.1 Metallodrugs with organotin(IV) compounds emerging as a potential alternative to platinum-based drugs have revolutionised the field of both diagnosis and therapy, offering enhanced anticancer efficacy and bio-imaging capabilities for targeting intracellular organelles.2,3 Even though non-platinum metal-based complexes have been extensively studied as anticancer agents, their fast hydrolysis, reduced hydrolytic stability, and cellular absorption render them unsuitable for the development of standard anticancer metallodrugs.4 In this presentation, we embarked on an effort to explore the theranostic potential of a new class of azo hydrazone-based organotin(IV) complexes [SnIVL1–4(Ph)2] (1–4). The aqueous stability, hydrophobic character, and interaction of 1−4 with biomolecule (BSA and DNA) were examined. The speciation studies suggested the complexes possess exceptional hydrolytic stability. Further in-depth mechanistic studies revealed that they preferentially accumulate in the lysosome, damage lysosomal membrane potential, and upregulate intracellular reactive oxygen species (ROS), leading to apoptotic-mediated cancer cell death.