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Anti-Cancer Agents in Medicinal Chemistry

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ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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Research Article

Half-Lantern Cyclometalated Platinum(II) Complexes as Anticancer Agents: Molecular Docking, Apoptosis, Cell Cycle Analysis, and Cytotoxic Activity Evaluations

Author(s): Fatemeh Hajipour, Masoud Mahdavinia and Masood Fereidoonnezhad*

Volume 22, Issue 6, 2022

Published on: 13 July, 2021

Page: [1149 - 1158] Pages: 10

DOI: 10.2174/1871520621666210713112105

Price: $65

Abstract

Background and Objective: In the design of modern metal-based anticancer drugs, platinum-based complexes have gained growing interest. In this study, the anticancer activity of half-lantern cyclometalated Pt(II)‒Pt(II) complexes was evaluated using MTT, apoptosis, cell cycle analysis, and DNA binding studies.

Materials and Methods: The cytotoxicity of Pt(II)‒Pt(II) complexes were evaluated against different cancer cell lines, such as human lung (A549), breast (MCF-7, and MDA-MB-231), ovarian (SKOV-3), and colon (HT-29) as well as normal breast (MCF-10A), and human lung fibroblast (MRC-5) cells using MTT assay. BioLegend's PE Annexin, V Apoptosis Detection Kit with 7AAD, was applied to assess the apoptotic effects of 1A and 1B compound against MCF-7 and A549 cell lines. Cell cycle analysis was determined using the flow cytometry method. The interaction of compounds with four different DNA structures with PDB codes (1BNA, 1LU5, 3CO3, and 198D) has been investigated by molecular docking. To achieve binding to DNA experimentally, the electrophoresis mobility shift assay and comet assay were applied.

Results: In the evaluation of cytotoxic effects, 1A showed the highest cytotoxicity among the studied compounds, and it showed higher potency with more selectivity against normal cell lines than cisplatin. This compound had IC50 of 7.24, 2.21, 1.18, 2.71, 10.65, 18.32, and 49.21 μM against A549, SKOV3, HT29, MCF-7, MDA-MB-231, MRC-5, and MCF-10A, respectively, whereas cisplatin had IC50 of 9.75, 19.02, 107.23, 15.20, 18.09, 14.36, and 24.21 μm, respectively, on the same cell lines. In order to check the DNA binding activity of 1A, and 1B, electrophoretic mobility was also conducted, which indicated that the binding of these compounds led to a slight change in electrophoretic mobility to DNA. The migration of chromosomal DNA from the nucleus in the form of a tail or comet was executed in the comet assay of 1A on MCF-7. Examination of apoptosis of 1A and 1B on the MCF-7 cancer cell line showed that it could increase induction of apoptosis in this cancerous cell in a concentration-dependent manner. Investigating the effect of 1A using cell cycle analysis on MCF-7 cancer cell line showed that this complex affects stage G1 and S of the cell cycle.

Conclusion: 1A has the potential to play a significant role in future biopharmaceutical studies.

Keywords: Half-lantern cyclometalated Pt(II)‒Pt(II) complexes, molecular docking, apoptosis, cytotoxic activity, cell cycle analysis, MTT.

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