Organotin(IV) compounds represent a unique class of organometallic complexes whose biological activity originates from the direct tin–carbon bond and is strongly influenced by the nature of the ligands and the number of organic substituents [1], [2]. Their structural diversity and capacity to interact with biologically relevant molecules make them promising candidates for the development of anticancer drugs [1], [2]. These compounds exhibit potent cytotoxic effects against a broad spectrum of cancer cell lines by disrupting multiple cellular processes, including DNA replication and transcription, induction of mitochondria-mediated apoptosis, generation of reactive oxygen species (ROS), and modulation of signalling pathways that regulate cell proliferation and survival [1], [2], [3]. Triorganotin(IV) derivatives are distinguished by enhanced lipophilicity, facilitating cellular uptake and contributing to superior anticancer activity compared to di- and monoorganotin(IV) analogues [2], [3]. Despite their high cytotoxic potential, clinical application of organotin(IV) compounds is often limited by nonspecific toxicity and accumulation in healthy tissues [4].

To overcome these limitations, targeted delivery strategies have emerged as effective approaches to improve selectivity and reduce systemic side effects [2]. Transferrin (Tf), a glycoprotein responsible for Fe3+ transport via receptor-mediated endocytosis, provides a natural mechanism for targeted delivery [5], [6], [7]. Beyond its role in drug delivery, Tf plays a critical role in systemic Fe3+ trafficking within the bloodstream, ensuring controlled distribution of this essential metal ion to cells and tissues. Structurally, Tf is composed of two major domains (N- and C-terminal), each capable of binding an Fe3+ ion. The protein without Fe3+ is termed apotransferrin (aTf), while the Fe3+-bound form is holotransferrin (hTf), and this transition governs its recognition by transferrin receptor 1 (TfR1) [6], [7], [8].

In this study, we present a comprehensive analysis of the anticancer activity of a series of previously synthesized compounds (propyl-3-ol)triphenyltin(IV) (Ph3SnL1), (butyl-4-ol)triphenyltin(IV) (Ph3SnL2), (octyl-8-ol)triphenyltin(IV) (Ph3SnL3), and (dodecyl-11-ol)triphenyltin(IV) (Ph3SnL4) in human cancer cell lines T47D (breast carcinoma), RKO (colorectal carcinoma), SAS (oral carcinoma), and ES2 (ovarian carcinoma) (Fig. 1) [9], [10].

Their cytotoxic potential was evaluated using standard cell viability assays (MTT and CV), while additional mechanistic studies focused on apoptosis induction, cell-cycle perturbation, autophagy, and intracellular ROS generation. Particular attention was given to the interaction of the investigated complexes with Tf, a key transport protein involved in iron metabolism and receptor-mediated drug uptake. In this study, Tf binding is explored as a complementary mechanistic aspect related to molecular recognition and potential TfR1-oriented targeting, rather than as functional proof of Tf-mediated cellular uptake or plasma transport dominance. Since cancer cells typically overexpress TfR1 due to increased metabolic demands, they preferentially internalise Tf-conjugated agents, enabling selective accumulation of cytotoxic complexes within malignant tissues [5], [6], [7]. These interactions were examined through a combination of experimental and computational approaches, including molecular docking simulation, to elucidate the role of protein binding in mediating anticancer activity. Furthermore, antimicrobial screening was performed to assess the broader biological potential and selectivity of the compounds. This multimodal approach enabled the establishment of a connection between cytotoxic effects, protein interactions, and molecular mechanisms of action, providing a foundation for the rational design of organotin(IV)-based anticancer agents. Integrating the intrinsic cytotoxicity of organotin(IV) derivatives with the natural targeting ability of Tf represents a promising strategy for developing safer, more selective, and more effective anticancer therapies.