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. 2020 Mar 12;11(5):940-948.
doi: 10.1021/acsmedchemlett.9b00676. eCollection 2020 May 14.

Highly Promising Antitumor Agent of a Novel Platinum(II) Complex Bearing a Tetradentate Chelating Ligand

Ismail Yılmaz  1 , Okan Remzi Akar  2 , Merve Erkisa  3 , Selin Selvi  2 , Abdurrahman Şengül  4 , Engin Ulukaya  3
Affiliations

Highly Promising Antitumor Agent of a Novel Platinum(II) Complex Bearing a Tetradentate Chelating Ligand

Ismail Yılmaz et al. ACS Med Chem Lett. .

Abstract

A new mononuclear cationic platinum(II) coordination compound with 6,6'-bis(NH-benzimidazol-2-yl)-2,2'-bipyridine (L) ligand having N4-tetradentate binding pocket [Pt(L)]Cl2·2H2O (Complex 1) was synthesized and characterized by FT-IR(ATR), UV-vis, 1H NMR, APCI and MALDI MS, and CHN analysis. The antigrowth effect of Complex 1 was tested in breast cancer (MDA-MB-231), lung cancer (A549), colorectal cancer (HCT-116), prostate cancer (PC-3) cell lines, and bronchial epithelial cell line (BEAS-2B) by the SRB and ATP cell viability assays. Apoptosis was detected with Annexin V, mitopotential, BCL-2 inactivation, and γH2AX assays by flow cytometry. Complex 1 was found to have cytotoxic activity of MDA-MB-231, A549, HCT-116, and PC-3 cancer cell lines in a dose-dependent manner for 48 h. Complex 1 has been found to cause cell death through different mechanisms depending on the type of cancer. The findings indicated that complex induced intrinsic apoptosis with the increased mitochondrial membrane depolarization level, Bcl-2 inactivation, and DNA damage in PC-3 and A549 cell lines.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Schematic Presentation of the Synthesis of Complex 1
Figure 1
Figure 1
Cell viability analysis of Complex 1 for 48 h against A549, PC-3, MDA-MB-231, HCT-116, and BEAS-2B cells measured by (A) SRB assay and (B) ATP assay. Cytotoxicity of ligand alone for 48 h against five cell lines detected by (C) SRB assay. *** denotes statistically significant differences in comparison with control (p < 0.001).
Figure 2
Figure 2
Determination of apoptosis in (A) A549, (B) MDA-MB-231, (C) PC-3, (D) HCT-116, and (E) BEAS-2B cell lines treated with Complex 1 (IC90 doses) for 24 and 48 h assessed by Annexin-V positivity.
Figure 3
Figure 3
Mitochondrial membrane depolarization was detected by the flow cytometer in (A) A549, (B) MDA-MB-231, (C) PC-3, (D) HCT-116, and (E) BEAS-2B cell lines after treatment with Complex 1 (IC90 doses) for 24 and 48 h.
Figure 4
Figure 4
Bcl-2 inactivation was detected by flow cytometer in (A) A549, (B) MDA-MB-231, (C) PC-3, (D) HCT-116, and (E) BEAS-2B cell lines after treatment with Complex 1 (IC90 doses) for 24 and 48 h.
Figure 5
Figure 5
DNA damage was detected via H2AX assay by a flow cytometer in (A) A549, (B) MDA-MB-231, (C) PC-3, (D) HCT-116, and (E) BEAS-2B cell lines after treatment with Complex 1 (IC90 doses) for 24 and 48 h.
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