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Objectives. To synthesize Pt-containing derivatives of natural chlorins as potential agents for the combination therapy in oncology. Platinum compounds are known to occupy an important place as chemotherapeutic agents in the treatment of oncological diseases. However, Pt(II) complexes are highly toxic to the body and are not selectively accumulated in tumor cells. If photodynamic and chemotherapy methods are combined in a single drug, the pigments are responsible for the selectivity of conjugate accumulation in the tumor, while a chemotherapeutic agent based on Pt(II) complexes is responsible for the cytotoxic effect on tumor cells. This will not affect healthy cells and thereby minimize the systemic toxicity of the drug to the body.Methods. Methods for the synthesis of pyridine-containing derivatives of natural chlorins and their metal complexes for use as potential binary agents in oncology were applied. As part of the study, the structures of the compounds obtained were confirmed by mass spectrometry, nuclear magnetic resonance spectroscopy, ultraviolet spectroscopy, and high-resolution chromatography-mass spectrometry. Preparative methods, including thin-layer and column chromatography, centrifugation and recrystallization, were used to isolate and purify the compounds obtained.Results. Platinum(II) complexes of pyridine-containing derivatives of natural chlorins were obtained for application in combination therapy in oncology. The schemes for synthesizing the target photosensitizers were optimized, in order to increase the yields and for subsequent transfer to industrial sites.Conclusions. It was found that pyridine-containing derivatives of natural chlorins could be obtained in high yields, that they possess chelating properties for platinum, and can be considered as binary agents in cancer therapy after successful preclinical trials.

In this experimental work the acute toxicity of a chemically modified derivative of the natural pigment chlorophyll a called monocationic chlorin e6, which is a promising photosensitizer (PS) for antimicrobial and antitumor photodynamic therapy, was studied using white rats. The advantages of the PS under investigation are an intense absorption in the long-wavelength region of the visible spectrum, a sufficiently high quantum yield of singlet oxygen generation, pronounced amphiphilic properties along with an appropriate solubility in water, and a high level of photocytotoxic- ity in relation to both malignant HeLa cells and antibiotic-resistant hospital strains of E. сoli bacteria., P. aerugenosa and others. It has been shown that the value of LD50 of the considered PS can be calculated as the value of 100 mg/kg. In the reproduced experimental model of acute toxicity, pathomorphological changes in the vital organs of laboratory animals indicate a pronounced vasopathic effect of the drug with the development of cerebral edema and respiratory distress syndrome, which have become the main signs of thanatogenesis.

Objectives. This study aims to obtain the amino acid derivatives of chlorophyll a and bacteriochlorophyll a for the targeted delivery of pigments to tumor foci. This will increase biocompatibility and, as a result, reduce toxic side effects. In addition to photodynamic efficiency, an additional cytotoxic effect is expected for the obtained conjugates of photosensitizers (PSs) with amino acids. This is owing to the participation of the latter in intracellular biochemical processes, including interaction with the components of the glutathione antioxidant system, leading to the vulnerability of tumor cells to oxidative stress.Methods. In this work, we have implemented the optimization of the structure of a highly efficient infrared PS based on O-propyloxim-N-propoxybacteriopurpurinimide (DPBP), absorbing at 800 nm and showing photodynamic efficacy for the treatment of deep-seated and pigmented tumors, by introducing L-lysine, L-arginine, methionine sulfoximine (MSO), and buthionine sulfoximine (BSO) methyl esters. The structure of the obtained compounds was proved by mass spectrometry and nuclear magnetic resonance spectroscopy, and the photoinduced cytotoxicity was studied in vitro on the HeLa cell line.Results. Conjugates of DPBP with amino acids and their derivatives, such as lysine, arginine, MSO, and BSO have been prepared. The chelating ability of DPBP conjugate with lysine was shown, and its Sn(IV) complex was obtained.Conclusions. Biological testing of DPBP with MSO and BSO showed a 5–6-fold increase in photoinduced cytotoxicity compared to the parent DPBP PS. Additionally, a high internalization of pigments by tumor cells was found, and the dark cytotoxicity (in the absence of irradiation) of DPBP-MSO and DPBP-BSO increased fourfold compared to the initial DPBP compound. This can be explained by the participation of methionine derivatives in the biochemical processes of the tumor cell.

Objectives. Chlorin and bacteriochlorin photosensitizers are effective agents for cancer photodynamic therapy and fluorescence imaging. They are also excellent chelators forming stable metal complexes. Besides, 64Cu and 109Pd isotopes can serve as emitters for nuclear medicine. Chelation of these metals with cyclen conjugates with chlorin and bacteriochlorin photosensitizers can become a simple and universal strategy for the synthesis of diagnostic and therapeutic radiopharmaceuticals for nuclear medicine. This article reports on the synthesis of similar Cu and Pd complexes of cyclen conjugates with pheophorbide and bacteriopheophorbide and the study of their photophysical properties.Methods. Metalation of cyclen conjugates was carried out with palladium and copper acetates. For bacteriochlorins, 6-O-palmitoyl-L-ascorbic acid was additionally used as a reducing agent. MALDI mass spectrometry, which was carried out on a time-of-flight mass spectrometer Bruker Ultraflex TPF/TOF and a Bruker Daltonics Autoflex II confirmed the structure of the compounds obtained Electronic absorption spectra were obtained on a Shimadzu 3101 spectrophotometer. Fluorescence and phosphorescence spectra were obtained on a FluoTime 300 PicoQuant spectrofluorometer.Results. Photophysical studies of metal complexes showed that the introduction of palladium cations quenches fluorescence and increases the quantum yield of singlet oxygen generation to 0.98 for the chlorin conjugate. Besides, it decreases the quantum yield of fluorescence to 0.10 and increases the quantum yield of singlet oxygen generation to 0.72 for the bacteriochlorin conjugate. Introducing a copper cation to cyclen conjugates with pheophorbide and bacteriopheophorbide leads to photophysical characteristics quenching.Conclusions. Due to the stability of the synthesized metal complexes in acidic media, as well as the short metalation time (5, 20, 10, and 15 minutes) it is reasonable to expect the successful development of effective imaging agents for positron emission tomography and radionuclide therapy. In addition, the residual fluorescence of bacteriochlorins makes it possible to use fluorescence diagnostics in combination with these methods.

Donor-acceptor systems based on 5-(p-aminophenyl)-10,15,20-triphenylporphyrin, purpurin 18 and 2-(2-hydroxyethyl)thio-3-methyl-1,4-naphthoquinone were synthesized to simulate the natural photoconverting systems. Their spectral properties were studied.