Homo- and heteroleptic Pt(II) complexes of ONN donor hydrazone and 4-picoline: A synthetic, structural and detailed mechanistic anticancer investigation
Abstract Two series of homoleptic Pt(II)(hydrazone)Cl ( C1a - C5a ) and heteroleptic Pt(II)(hydrazone)(4-picoline). BF 4 ( C1b - C5b ) complexes were prepared and characterized by 1 H, 13 C, 19 F NMR and HR ESI-MS. Structure of C2b was confirmed by single crystal X-ray analysis. These complexes were studied for their in vitro anticancer activities in human multiple cancer cells including breast (MCF-7), liver (HepG2), lung (H460), colon (HCT116) and cervical (Hela) cancers. C1a - C5a and C1b - C5b showed considerable anticancer effect. The overall anticancer effect of all these complexes was higher in liver (HepG2) and lung (H460) cancer cell lines and the effect of C2b and C3b was observed to be the highest among these 10 complexes. Therefore, we selected C2b and C3b to study their in vitro anticancer mechanism in HepG2 and H460 cancer cells. C2b and C3b changed cancer cell morphology and inhibited cell migration. The anticancer mechanistic studies demonstrated that C2b and C3b induced cell apoptosis, as evidenced by DAPI and AO/EB staining and flow cytometry analyses. Moreover, qRT-PCR and western blotting analysis showed that H460 and HepG2 cells treated with C2b and C3b significantly increased the expression of p53, p63, p21, p15, Bax and decreased Bcl-2 and c-Myc levels. The DNA binding property of these complexes was investigated by gel electrophoresis using pBR322 plasmid DNA. Taken together, the results obtained from the present study demonstrated the potentials of this new class of Pt(II) complexes in reduction of cell viability, suppression of cell migration and acceleration of apoptosis in different cancer cells. Highlights Pt(II) complexes of ONN donor hydrazone ligand. Homo- and hetero-leptic Pt(II) complexes. In vitro anticancer study in multiple cancer cells. Mechanistic insight to the anticancer effect. DNA interaction study of Pt(II) complexes. Graphical abstract [DISPLAY OMISSION]
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