Effect of geometric isomerism on the anticancer property of new platinum complexes with glycine derivatives as asymmetric N, O donate ligands against human cancer

• Published in: Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy Molecular and biomolecular spectroscopy, 2024-12, Vol.322, p.124809, Article 124809
• Main Authors: Kadivar, Diba, Eslami Moghadam, Mahboube, Notash, Behrouz
• Format: Article
• Language: English
• Subjects: Anticancer Pt compounds; Asymmetric bidentate ligand; Cis- and trans-isomers; Cytotoxicity; Geometric Isomerism effect; Glycine
• ISSN: 1386-1425
• DOI: 10.1016/j.saa.2024.124809

The biological activity of some Pt(II) complexes with bidentate asymmetric R-glycine ligands were evaluated and they were specified by using various techniques and single-crystal X-ray diffraction. The cytotoxicity of these compounds was tested on three different cancerous cell lines (MCF7, A549, A375) and one normal cell line (HFF). Additionally, to follow the isomerism effect and structure-bioactivity relationship, DFT calculations, MEP analysis, spectroscopic method, and molecular docking simulations were studied for designing new anticancer agents. [Display omitted] •Six new isomers of Pt complexes with glycine derivatives were synthesized.•All structures were proved by using FT-IR, UV–Vis, Mass, 1H NMR, 13C NMR, 195Pt NMR, LC-Mass, Raman, and single-crystal X-ray diffraction.•Cytotoxicity ability was evaluated on three cancerous (A549, MCF7, and A375) and one normal (HFF) cell lines.•The mode of DNA binding was investigated by spectroscopic method and molecular docking simulation. In this project, to fallow the anticancer ability of new Pt drugs, several new Pt complexes were synthesized with the asymmetric bidentate glycine derivatives, as named propyl- and hexyl glycine (L), in the general formula: [Pt(NH3)2(L)]NO3, and cis- and trans-[Pt(L)2]. The structure of two cis- and trans-[Pt(propylgly)2] complexes was proved by single crystallography analysis. However, all complex structures were characterized by various methods of 1H NMR, 13C NMR, 195Pt NMR, FTIR, LC-Mass, and Raman spectroscopy. To study the passage of water-soluble complexes of [Pt(NH3)2(L)]NO3 via cell membrane, their solubility, and lipophilicity were analyzed. In addition, the cytotoxic properties of these complexes were evaluated against normal and malignant cell lines (skin, breast, and lung cancer cells). The results indicated that they were either comparable to cisplatin or less damaging than carboplatin and oxaliplatin. It was expected that due to less steric effect, and the presence of length aliphatic hydrocarbon chain in the complex structure, trans-[Pt(hexylgly)2] is more toxic on cancerous cell lines than trans-[Pt(propylgly)2]. Cellular accumulation of all complexes was evaluated on A549 and MCF7 cell lines, and the amount of platinum metal (ng) was measured by the ICP method. Results showed that trans-[Pt(hexylgly)2] complex has the highest accumulation inside both mentioned cell lines and [Pt(NH3)2(L)]NO3 complexes behave like clinical Pt-drugs. Ultimately, the interactio