Tin Carboxylate Complexes of Natural Bacteriochlorin for Combined Photodynamic and Chemotherapy of Cancer è

International Journal of Molecular Sciences

卷:22

Andrey Mironov¹  Petr Ostroverkhov¹  Sergey Tikhonov¹  Mikhail Grin¹  Nikita Suvorov¹  Yulia Efimova¹  Yuriy Vasil’ev²  Ekaterina Diachkova³  Alexey Feofanov⁴  Anastasia Ignatova⁴  Anna Plutinskaya⁵  Andrei Pankratov⁵ 

[1] Department of Chemistry and Technology of Biologically Active Compounds, Medicinal and Organic Chemistry, Institute of Fine Chemical Technologies, MIREA-Russian Technological University, 86 Vernadsky Avenue, 119571 Moscow, Russia;

[2] Department of Operative Surgery and Topographic Anatomy, I.M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya St. Building 8\2, 119991 Moscow, Russia;

[3] Department of Oral Surgery of Borovsky Institute of Dentistry, I.M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya St. Building 8\2, 119991 Moscow, Russia;

[4] Laboratory of Optical Microscopy and Spectroscopy of Biomolecules of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Mikluko-Maklaya St. 16/10, 117997 Moscow, Russia;

[5] P. Hertsen Moscow Oncology Research Institute—Branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, 2nd Botkinsky pr. 3, 125284 Moscow, Russia;

关键词: PDT;    bacteriochlorin;    chemotherapy;    cancer;    tin carboxylates;   

DOI  :  10.3390/ijms222413563

来源: DOAJ

【 摘 要 】

Photodynamic therapy (PDT) is currently one of the most promising methods of cancer treatment. However, this method has some limitations, including a small depth of penetration into biological tissues, the low selectivity of accumulation, and hypoxia of the tumor tissues. These disadvantages can be overcome by combining PDT with other methods of treatment, such as radiation therapy, neutron capture therapy, chemotherapy, etc. In this work, potential drugs were obtained for the first time, the molecules of which contain both photodynamic and chemotherapeutic pharmacophores. A derivative of natural bacteriochlorophyll a with a tin IV complex, which has chemotherapeutic activity, acts as an agent for PDT. This work presents an original method for obtaining agents of combined action, the structure of which is confirmed by various physicochemical methods of analysis. The method of molecular modeling was used to investigate the binding of the proposed drugs to DNA. In vitro biological tests were carried out on several lines of tumor cells: Hela, A549, S37, MCF7, and PC-3. It was shown that the proposed conjugates of binary action for some cell lines had a dark cytotoxicity that was significantly higher (8–10 times) than the corresponding metal complexes of amino acids, which was explained by the targeted chemotherapeutic action of the tin (IV) complex due to chlorin. The greatest increase in efficiency relative to the initial dipropoxy-BPI was found for the conjugate with lysine as a chelator of the tin cation relative to cell lines, with the following results: S-37 increased 3-fold, MCF-7 3-fold, and Hela 2.4-fold. The intracellular distribution of the obtained agents was also studied by confocal microscopy and showed a diffuse granular distribution with predominant accumulation in the near nuclear region.

【 授权许可】

Unknown