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Eur J Med Chem. 2017 May 5;131:263-274. doi: 10.1016/j.ejmech.2017.03.014. Epub 2017 Mar 18.

Morpholine or methylpiperazine and salicylaldimine based heteroleptic square planner platinum (II) complexes: In vitro anticancer study and growth retardation effect on E. coli.

Author information

1
Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, China; Department of Materials Science, Fudan University, 220 Handan Road, Shanghai 200433, China.
2
Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China; Institute of Integrative Biosciences, CECOS University of IT and Emerging Sciences, Peshawar, KPK, Pakistan.
3
Laboratory of Molecular Biology and Immunology, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, 220 Handan Road, Shanghai 200433, China.
4
Institute of Research and Development, Duy Tan University, K7/25 Quang Trung, Danang 59000, Vietnam; Department of Cancer Research, Vinmec Research Institute of Stem Cell and Gene Technology, 458 Minh Khai, Hanoi 10000, Vietnam.
5
Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, China.
6
Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, China. Electronic address: wanghui@fudan.edu.cn.
7
Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, China. Electronic address: zhangdw@fudan.edu.cn.

Abstract

Morpholine and methylpiperazine are among the most important structural parts of different drugs including organic chemotherapeutic agents. In the current study we incorporated these entities as co-ligand and a series of structurally related mono- and di-metallic square planner Pt(II) complexes (Pt(II)(salicylaldimine)(morpholine)Cl C1a-C3a, Pt(II)(salicylaldimine) (methylpiperazine)Cl C1b-C3b, di-metallic Pt(II)2(bis-salicylaldimine)(morpholine)2Cl2C4a and Pt(II)2(bis-salicylaldimine)(methylpiperazine)2Cl2C4b were prepared. These complexes were characterized by 1H, 13C, 19F, 2D NOESY NMR, HR ESI-MS and elemental analyses, while structures of C2a, C3a and C4b were determined by single crystal X-ray analysis. All these complexes were studied for their in vitro cytotoxic effect on breast (MCF-7), liver (HepG2) and lung (A549) cancer cell lines. All these complexes showed considerable cytotoxic effect on these tested cancer cell lines comparable to cisplatin. Moreover three complexes C1a, C4a and C1b were studied in details. Time- and dose-dependent study was performed for C1a, C4a and C1b. These complexes induced the expression of p53 that suppresses cancer cell growth. Induction of PUMA gene and repression of MYC oncogene suggested that these complexes targeted different genes to suppress cancer progression. TUNEL assay showed induction of apoptosis and invasion analysis showed reduction in invasion ability of breast cancer cells treated with C1a, C4a or C1b. Importantly, these novel complexes suppressed the expression of EMT and metastasis promoter genes. Similarly these complexes induced autophagy by enhancing the expression of autophagy related genes such as beclin, atg-5 and atg-7. The E. coli growth retardation study showed stronger growth inhibitory effects and subsequently resulted in filamentous morphology of bacterial cells. Gel electrophoresis study proved the interaction of these complexes with DNA. All these analysis revealed anticancer potencies of this class of complexes.

KEYWORDS:

Anticancer Pt(II) complexes; Cytotoxicity; DNA interaction; Effect on E. coli growth; Gel electrophoresis

PMID:
28334655
DOI:
10.1016/j.ejmech.2017.03.014
[Indexed for MEDLINE]

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