Development of natural chlorin-based photoactivatable Pt(II) and Pt(IV) complexes.

Platinum-based chemotherapeutic agents are widely used in the treatment of various solid tumors. However, Pt(II) compounds have a number of limitations, such as insufficient selectivity of accumulation and action, which leads to numerous adverse effects. It is also known about drug resistance of tumor cells, resulting in reduced platinum accumulation and activation of DNA repair systems. The development of novel platinum-based anticancer agents remains a critical challenge in modern medicinal chemistry.

Unlike Pt(II) complexes, Pt(IV) compounds are kinetically inert and can serve as prodrugs. Upon reduction within the cell by intracellular reducing agents (glutathione, ascorbic acid) or by exposure to light of a specific wavelength, Pt(IV) complex releases not only the cytotoxic moiety but also two axial ligands, which may themselves possess biological activity.

Another strategy to minimize side effects involves the use of photocaged molecules in therapy. This approach significantly enhances the selectivity and efficacy of cancer treatment while reducing systemic toxicity through targeted activation of the molecule at the lesion site.

This study focuses on the development of photoactivatable Pt(II) and Pt(IV) complexes using natural chlorin-based photosensitizers as vector molecules characterized by high affinity for tumor tissue. The obtained compounds were analyzed using a set of physicochemical methods (NMR spectroscopy, mass-spectrometry, studies on determining the quantum yield of singlet oxygen and LogP), and their structures were reliably confirmed by high‑resolution chromatography–mass spectrometry. At the current stage, primary in vitro cytotoxicity studies and intracellular accumulation are being evaluated using the A549 lung adenocarcinoma cell line.