trans‐Platinum(II) Thionate Complexes: Synthesis, Structural Characterization, and in vitro Biological Assessment as Potent Anticancer Agents

Abstract

A series of Pt(II) complexes trans‐[Pt(PPh2allyl)2(κ1‐S‐SR)2], 1, PPh2allyl=allyldiphenylphosphine, SR=pyridine‐2‐thiol (Spy, 1 a), 5‐(trifluoromethyl)‐pyridine‐2‐thiol (SpyCF3‐5, 1 b), pyrimidine‐2‐thiol (SpyN, 1 c), benzothiazole‐2‐thiol (Sbt, 1 d), benzimidazole‐2‐thiol (Sbi, 1 e), were synthesized. They were characterized by NMR, HR ESI‐MS, and X‐ray crystallography. Treatment of human cancer cell lines (A549, SKOV3, MCF‐7) with these complexes resulted in promising antitumor effects in comparison with cisplatin. These compounds showed suitable selectivity between tumorigenic and non‐tumorigenic (MCF‐10 A) cell lines. Analyses of cell cycle progression and apoptosis were conducted for 1 a, the most cytotoxic compound, to screen dose/time response and to study the antiproliferative mechanism. An electrophoresis mobility shift assay was performed to assess the direct interaction of 1 a with DNA and the strong genotoxic ability was indicated through the comet assay method.

The Challenging Treatment of Cisplatin-Resistant Tumors: State of the Art and Future Perspectives

“…The advantage of this approach is that there are different structural and DNA-binding properties in comparison with cisplatin and its derivatives, which notably possesses a cis arrangement of ligands around the metal center. For this reason, a series of trans-Pt(II) complexes (complex 1) with heterocyclic thionate ligands has been synthesized (Figure 2) [31]. All of these new complexes have been tested on three human cancer cell lines (A549 lung, SKOV3 ovarian, and MCF-7 breast cancer cell lines) and studied for their antiproliferative activities in comparison with cisplatin and complex 2, a dichloride Pt(II) complex counterpart in a cis conformation (Figure 3).…”

Fluorinated Cycloplatinated(II) Complexes Bearing Bisphosphine Ligands as Potent Anticancer Agents

“…In addition, in order to check the selectivity between cancer and normal cell lines, the effects of these compounds on the proliferation of MCF-10A were also determined on the basis of the procedure of our reported work . As summarized in Table , all of these compounds displayed fair selectivity between tumorigenic and nontumorigenic cell lines.…”

“…The docked pose visualization was performed by means of AutoDock Tools 1.5.6 and Molecular Operating Environment (MOE). 68…”

“…The lowest docking binding energy conformation was chosen as the best binding mode with respect to the AutoDock scoring features. The docked pose visualization was performed by means of AutoDock Tools 1.5.6 and Molecular Operating Environment (MOE) …”

ROS‐Mediated Antitumor Activity, Apoptosis, and Molecular Docking Studies of Platinum(II) Coordination Complexes Bearing 2‐(Diphenylphosphino)pyridine Ligands

“…Nevertheless, there are often limited studies on platinumphosphine complexes for pharmaceutical purposes specifically, compared to the nitrogen ligands. [16][17][18][19] As a continuation of our ongoing interest in the biological investigation of Pt(II) complexes, [20][21][22][23][24][25][26][27] herein, we designed to evaluate the anticancer activities of Pt(II) coordination complexes comprising 2-(diphenylphosphino)pyridine (dppy) dangling/bridging ligand as one of the most attractive phosphine compounds which plays a vital role in coordination and organometallic chemistry, and exhibit various physical or chemical properties according to the presence of different coordination modes. [28,29] Hence, a series of Pt(II) coordination complexes with a general formula of (cis-PtL 2 X 2 ), L = dppy and X=Cl, Me [30,31] and p-tolyl [31] were biologically investigated to have antitumor properties.…”