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

The development of sulfur-containing pharmaceutical compounds is important in the advancement of medicinal chemistry. Photosensitizers (PS) that acquire new properties upon incorporation of sulfur-containing groups or individual sulfur atoms into their structure are not neglected, either. In this work, a synthesis of sulfur-containing derivatives of natural chlorophyll a using Lawesson's reagent was optimized. Thiocarbonyl chlorins were shown to have a significant bathochromic shift in the absorption and fluorescence bands. The feasibility of functionalizing the thiocarbonyl group at the macrocycle periphery by formation of a Pt(II) metal complex in the chemotherapeutic agent cisplatin was shown. The chemical stability of the resulting conjugate in aqueous solution was studied, and it was found to possess a high cytotoxic activity against sarcoma S37 tumor cells that results from the combined photodynamic and chemotherapeutic effect on these cells.

Advantages of combined photodynamic therapy in the treatment of oncological diseases.

When conducting combined therapy of malignant neoplasms, treatment methods with various mechanisms of antitumor effects are used, while an additive or even synergistic effect can be realized. Combination treatment regimens are aimed at increasing the efficiency and, above all, at the complete eradication of the tumor, which can be achieved either by suppressing the survival mechanisms in PDT-resistant tumor cells or by pre-attenuation of tumor cells so that they become more susceptible to subsequent PDT. Photodynamic therapy is an approved medical technology for the treatment of various malignant neoplasms, and several precancerous and non-cancer diseases. To date, numerous data have been published on the combined use of PDT with traditional and innovative methods of treatment. This review considers research in this area in recent years.

The First Selenoanhydride in the Series of Chlorophyll a Derivatives, Its Stability and Photoinduced Cytotoxicity.

In this work, we obtained the first selenium-containing chlorin with a chalcogen atom in exlocycle E. It was shown that the spectral properties were preserved in the target compound and the stability increased at two different pH values, in comparison with the starting purpurin-18. The derivatives have sufficiently high fluorescence and singlet oxygen quantum yields. The photoinduced cytotoxicity of sulfur- and selenium-anhydrides of chlorin p6 studied for the first time in vitro on the S37 cell line was found to be two times higher that of purpurin-18 and purpurinimide studied previously. Moreover, the dark cytotoxicity increased four-fold in comparison with the latter compounds. Apparently, the increase in the dark cytotoxicity is due to the interaction of the pigments studied with sulfur- and selenium-containing endogenous intracellular compounds. Intracellular distributions of thioanhydride and selenoanhydride chlorin p6 in S37 cells were shown in cytoplasm by diffusion distribution. The intracellular concentration of the sulfur derivative turned out to be higher and, as a consequence, its photoinduced cytotoxicity was higher as well.

Derivatives of Natural Chlorophylls as Agents for Antimicrobial Photodynamic Therapy.

The rapid growth of drug-resistant bacteria all over the world has given rise to a major research challenge, namely a search for alternative treatments to which bacteria will be unable to develop resistance. Photodynamic therapy is an approach of this kind. It involves the use of photosensitizers in combination with visible light at a certain wavelength to excite the former and generate reactive oxygen species. Various synthetic heterocyclic compounds are used as photosensitizers. Of these, derivatives of natural chlorophylls have a special place due to their properties. This review deals with the use of such compounds in antimicrobial PDT.