Potential agents for combined photodynamic and chemotherapy in oncology based on Pt(II) complexes and pyridine-containing natural chlorins

Abstract

Combined therapy is currently a popular method for increasing the efficiency of antitumor treatment. It involves the use of two different tumor treatment methods, namely, chemotherapy and PDT. Combining a cytotoxic agent and a photosensitizer in a single molecule results in a synergistic antitumor effect that overcomes the multiple drug resistance and reduces the therapeutic drug doses. In this work, pyridine-containing natural chlorins were obtained by introducing a pyridine group into 131-[Formula: see text]-(4-aminobutyl)amide of chlorin [Formula: see text] and its bacteriochlorin analogue, [Formula: see text]-propyloxime-[Formula: see text]-propoxybacteriopurinimide as well as [Formula: see text]-aminobacteriopurinimide methyl ester. Moreover, a terpyridine residue was introduced as an external chelating moiety into [Formula: see text]-hydroxypurpurinimide and [Formula: see text]-aminobacteriopurinimide, and platinum complexes of all the above photosensitizers were obtained. The interactions of the latter with DNA were simulated and the lead compound, the platinum complex of pyridine derivative 131-[Formula: see text]-(4-aminobutyl)amide chlorin [Formula: see text], which may become a potential agent for combined photodynamic and chemotherapy in oncology, was selected. The ability of the compounds obtained to manifest photodynamic and chemocytotoxic effects on tumor cells of various genesis was shown.

Thiocarbonyl Derivatives of Natural Chlorins: Synthesis Using Lawesson’s Reagent and a Study of Their Properties

“…Previously, metal complexes of chlorins with platinum were obtained by our team by incorporating chelators based on nicotinic acid, isonicotinic acid, terpyridine, etc., into the PS structure [ 41 ]. It is known that apart from the nitrogen atom, the sulfur atom also tends to chelate d-metals due to transfer of unshared electron pairs of the chalcogen to the free orbitals of the metal.…”