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

Abstract

Following previous studies devoted to trans-Pt(3-af) 2 Cl 2 , 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) 2 Cl 2 . 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) 2 Cl 2 . 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.

Synthesis of Platinum(II) Complexes with Some 1-Methylnitropyrazoles and In Vitro Research on Their Cytotoxic Activity

“…Pharmaceuticals 2020, 13, x FOR PEER REVIEW 3 of 23 drugs can be distinguished, including trans platinum(II) analogs [11][12][13][14][15][16][17][18][19][20], Pt(IV) derivatives [21,22] polynuclear Pt complexes [23,24], Pt complexes with N-heterocyclic ligands [25], N-heterocyclic carbenes and cyclometallated Pt complexes [8], Pt(II) compounds with sulfur and phosphorus donors [26], compounds with leaving groups other than chlorido ligands [27]. However, it is necessary to emphasize that none of the trans Pt(II) and Pt(IV) complexes have been officially registered as anticancer drugs so far.…”

“…Although these findings can still be useful in the development of new platinum complexes with anticancer properties, starting in the early 1990s, numerous compounds have broken the rules mentioned above and have been synthesized and biologically tested with promising results [ 1 , 8 , 9 , 10 , 11 , 12 ]. Several classes of such non-classical (or non-conventional) platinum drugs can be distinguished, including trans platinum(II) analogs [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ], Pt(IV) derivatives [ 21 , 22 ] polynuclear Pt complexes [ 23 , 24 ], Pt complexes with N -heterocyclic ligands [ 25 ], N -heterocyclic carbenes and cyclometallated Pt complexes [ 8 ], Pt(II) compounds with sulfur and phosphorus donors [ 26 ], compounds with leaving groups other than chlorido ligands [ 27 ]. However, it is necessary to emphasize that none of the trans Pt(II) and Pt(IV) complexes have been officially registered as anticancer drugs so far.…”

Diversity-Oriented Synthesis: Amino Acetophenones as Building Blocks for the Synthesis of Natural Product Analogs

“…Among the structural modifications operated on flavonoids, the introduction of amino groups at the flavone scaffold was one of the most frequent [29][30][31][32]. For example, flavone derivatives bearing amino groups were studied as anticancer compounds [33][34][35][36]. Among them, flavopiridol was the first cyclin-dependent kinase inhibitor to enter human clinical trials [36].…”