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

Abstract

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.

Photodynamic Therapy: From the Basics to the Current Progress of N-Heterocyclic-Bearing Dyes as Effective Photosensitizers

“…The combined action, particularly of 3-bromopyruvate, with the excellent photobiological properties of the PS, studied in mice with large subcutaneous CT26 tumors, showed cure rates that were 22% higher than using Redaporfin alone and 33% higher than using only the glycolysis inhibitor. Conjugation with chemotherapeutics such as erlotinib [209], the introduction of groups that allow improvements in their biocompatibility through hydrophilicity enhancement (e.g., Trizma and spermine groups [210,211]), and the functionalization of bacteriochlorins of natural origin or the design of new bioinspired bacteriochlorins [199,212], are other approaches described in recent works that deserve the scientific community's attention.…”

“…In the field of oncology, and among the previously mentioned works, the study by Conjugation with chemotherapeutics such as erlotinib [209], the introduction of groups that allow improvements in their biocompatibility through hydrophilicity enhancement (e.g., Trizma and spermine groups [210,211]), and the functionalization of bacteriochlorins of natural origin or the design of new bioinspired bacteriochlorins [199,212], are other approaches described in recent works that deserve the scientific community's attention.…”

Designing and Exploration of the Biological Potentials of Novel Centrosymmetric Heteroleptic Copper(II) Carboxylates

“…The molecular docking study was performed using the MOE (2016) software. The 3D structure of alpha-amylase with PDB ID (3BAJ) and salmon sperm DNA (1BNA) was retrieved from the protein databank (PDB) database [58,59]. All the water molecules were removed prior to energy minimization.…”

The Organotin Applications in Biological, Industrial and Agricultural Sectors: A Systematic Review

“…Several researchers have identified complexes that are effective as antifouling, antibacterial, and antiviral drugs in recent years, therefore their applications for antioncogenesis have gotten a lot of interest. Organotin were the first identified organotin compounds with some cancer activity [29]. Yousif's group recently synthesized a di-organotin (IV) complex with valsartan as a ligand, and this compound demonstrated outstanding inhibitory effectiveness of A549 cells [30].…”