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Design of DNA-intercalators based copper(II) complexes, investigation of their potential anti-cancer activity and sub-chronic toxicity.
- Source :
-
Materials science & engineering. C, Materials for biological applications [Mater Sci Eng C Mater Biol Appl] 2019 Dec; Vol. 105, pp. 110079. Date of Electronic Publication: 2019 Aug 14. - Publication Year :
- 2019
-
Abstract
- In the present paper, we synthesized and characterized four N-donor polypyridyl copper(II) complexes (C1-C4); [Cu(mono-CN-PIP) <subscript>2</subscript> ] <superscript>2+</superscript> (C1), [Cu(tri-OMe-PIP) <subscript>2</subscript> ] <superscript>2+</superscript> (C2), [Cu(di-CF <subscript>3</subscript> -PIP) <subscript>2</subscript> ] <superscript>2+</superscript> (C3) and [Cu(DPPZ) <subscript>2</subscript> ] <superscript>2+</superscript> (C4). The (Calf-Thymus) CT-DNA binding studies depicted that the complexes could interact with DNA via intercalative mode. All the complexes, particularly C3 and C4 attenuated the proliferation as well as migration of various cancer cells, indicating their anti-cancer and anti-metastatic activity. Additionally, chick embryo angiogenesis (CEA) assay exhibited the inhibition of vascular sprouting in presence of C3 and C4, suggesting their potential in inhibiting the blood vessel growth. Mechanistic studies revealed that the complexes induced the excessive production of cellular reactive oxygen species (ROS) leading to apoptosis through up regulation of p53 and downregulation of Bcl-xL, which might be the plausible mechanisms underlying their anti-cancer properties. To understand the feasibility of practical application of anti-cancer copper complexes C3 and C4, in vivo sub-chronic toxicity study (4 weeks) was performed in C57BL6 mice and the results exhibited almost non-toxic effects induced by these complexes in terms of haematology and serum biochemical analyses, suggesting their biocompatible nature. The current study provides the basis for future advancement of other novel biocompatible metal complexes that could be employed for the therapy of different cancers.<br /> (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Antineoplastic Agents chemical synthesis
Antineoplastic Agents chemistry
Antineoplastic Agents pharmacokinetics
Cell Line, Tumor
Chick Embryo
Humans
Mice
Tumor Suppressor Protein p53 metabolism
bcl-X Protein metabolism
Coordination Complexes chemical synthesis
Coordination Complexes chemistry
Coordination Complexes pharmacology
Copper chemistry
Copper pharmacology
Intercalating Agents chemical synthesis
Intercalating Agents chemistry
Intercalating Agents pharmacology
Melanoma, Experimental drug therapy
Melanoma, Experimental metabolism
Melanoma, Experimental pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-0191
- Volume :
- 105
- Database :
- MEDLINE
- Journal :
- Materials science & engineering. C, Materials for biological applications
- Publication Type :
- Academic Journal
- Accession number :
- 31546406
- Full Text :
- https://doi.org/10.1016/j.msec.2019.110079