Triorganotin complexes in cancer chemotherapy: Mechanistic insights and future perspectives

Abstract

Current anticancer drug discovery and development efforts are aimed at identifying new complexes that can potently and selectively target DNA and modulate the functions of target proteins. Tin complexes, categorized as monoorganotin (RSnL3), diorganotin (R2SnL2), triorganotin (R3SnL), or tetraorganotin (R4SnL), are one of the most studied complexes in the metal‐based anticancer drug discovery and development field. Among these, diorganotins and triorganotins are widely reported to possess promising anticancer properties, with triorganotins offering several potential advantages over diorganotins, such as a higher total surface area causing higher lipophilicity and hence higher cytotoxicity in cancer cells. However, information on triorganotins' direct therapeutic targets, an in‐depth understanding of their mechanism of action, and useful therapeutic strategies are still lacking. In this review, we discuss the results from in vitro and in vivo mechanistic studies of triorganotin complexes as reported in recent years (2007–2019) and elaborate on the underlying mechanisms that could aid in the identification of triorganotin complex molecular targets. We conclude by identifying present obstacles faced by triorganotin complexes that avert their translation to the clinical phase and current strategies employed to overcome the aforementioned obstacles, and we offer considerations for their future development. These findings are anticipated to stimulate further developments of novel and innovative triorganotin complexes as anticancer drug candidates.