Open AccessHighly Promising Antitumor Agent of a Novel Platinum(II) Complex Bearing a Tetradentate Chelating Ligand
Author(s) -
İsmail Yılmaz,
Remzi Okan Akar,
Merve Erkısa,
Selin Selvi,
Abdurrahman Şengül,
Engı̇n Ulukaya
Publication year - 2020
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/acsmedchemlett.9b00676
Subject(s) - apoptosis , annexin , chemistry , cytotoxicity , cancer cell , flow cytometry , cell culture , a549 cell , ligand (biochemistry) , microbiology and biotechnology , cancer research , chelation , cancer , stereochemistry , biochemistry , biology , in vitro , receptor , medicine , organic chemistry , genetics
A new mononuclear cationic platinum(II) coordination compound with 6,6'-bis(NH-benzimidazol-2-yl)-2,2'-bipyridine ( L ) ligand having N 4 -tetradentate binding pocket [Pt( L )]Cl 2 ·2H 2 O ( Complex 1 ) was synthesized and characterized by FT-IR(ATR), UV-vis, 1 H 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.