Studies on new platinum complexes with trans-geometry

Abstract

Four Trans-planaramineplatnium(II) complexes code named: YH9, YH10, YH11 and YH12 of the form trans-PtL(NH3)CI2 , where L = 2-hydroxypyridine, imidazole, 3- hydroxypyridine and imidazo(l,2-a)pyridine respectively, have been prepared and characterised based on elemental analyses, IR, Raman, mass and ’H NMR spectral measurements. The activity of the compounds against a number of human cancer cell lines, cell uptake, DNA-binding and nature of interaction with pBR322 plasimd DNA and salmon sperm DNA have been determined. There is a wide variation in the activity of the compounds depending on the nature of the planaramine ligand illustrating structure-activity relationship. YH12, i.e. the compound having imidazo(l,2-a)pyridine ligand as one of the carrier ligands in the trans-configuration is found to be significantly more active than cisplatin against ovarian A2780cisR cancer cell line corresponding with higher Pt-DNA binding. The compound is more active in the cisplatin-resistant cell line A2780clsR than cisplatin-responsive cell line A2780, indicating that YH12 has been able to overcome multiple mechanisms of cisplatin resistance operating in A2780clsR cell line. All other compounds have resistance factors less than that for cisplatin in the A2780 and A2780clsR cell lines. A greater prevention of BamHl digestion with increasing concentration of the compounds indicates that as the compounds bind with nucleobases in DNA, the DNA conformation is changed sufficiently so as to prevent BamHl digestion at the specific GG site. Gel electrophoresis results also indicate that as the compounds bind to DNA, unwinding of supercoiled form I DNA takes place to change it from the negatively supercoiled form I through relaxed circular form I to the positively supercoiled form I.