Simple Trans-Platinum Complex Bearing 3-Aminoflavone Ligand Could Be a Useful Drug: Structure-Activity Relationship of Platinum Complex in Comparison with Cisplatin

含有 3-氨基黄酮配体的简单反式铂配合物可能是一种有用的药物:铂配合物与顺铂的构效关系比较

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作者:Małgorzata Fabijańska, Magdalena Orzechowska, Agnieszka J Rybarczyk-Pirek, Justyna Dominikowska, Alicja Bieńkowska, Maciej Małecki, Justyn Ochocki

Abstract

Following previous studies devoted to trans-Pt(3-af)2Cl2, in this paper, the molecular structure and intermolecular interactions of the title complex are compared with other cisplatin analogues of which the crystal structures are presented in the Cambridge Structural Database (CSD). Molecular Hirshfeld surface analysis and computational methods were used to examine a possible relationship between the structure and anticancer activity of trans-Pt(3-af)2Cl2. The purpose of the article was also to investigate the effect of hyperthermia on the anticancer activity of cisplatin, cytostatics used in the treatment of patients with ovarian cancer and a new analogue of cisplatin-trans-Pt(3-af)2Cl2. The study was conducted on two cell lines of ovarian cancer sensitive to Caov-3 cytostatics and the OVCAR-3 resistant cisplatin line. The study used the MTT (3-(4,5-dimethylthiazol-2,5-diphenyltetrazolium bromide) cell viability assay, LDH (lactate dehydrogenase), and the quantitative evaluation method for measuring gene expression, i.e., qPCR with TagMan probes. Reduced survivability of OVCAR-3 and Caov-3 cells exposed to cytostatics at elevated temperatures (37 °C, 40 °C, 43 °C) was observed. Hyperthermia may increase the sensitivity of cells to platinum-based antineoplastic drugs and paclitaxel, which may be associated with the reduction of gene expression related to apoptotic processes.

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