Improvement of the Anticancer Activities of Telmisartan by Zn(II) Complexation and Mechanisms of Action
To improve the anticancer activity of telmisartan, its structure has been modified by Zn(II) complexation giving [Zn(Telm) 2 (H 2 O) 2 ]·2H 2 O (ZnTelm). The cytotoxic effect was measured on the human lung cancer cells (A549) and on the lung fibroblast cells (MRC-5). The complex markedly improved an...
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Published in | Biological trace element research Vol. 197; no. 2; pp. 454 - 463 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
New York
Springer US
01.10.2020
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | To improve the anticancer activity of telmisartan, its structure has been modified by Zn(II) complexation giving [Zn(Telm)
2
(H
2
O)
2
]·2H
2
O (ZnTelm). The cytotoxic effect was measured on the human lung cancer cells (A549) and on the lung fibroblast cells (MRC-5). The complex markedly improved anticancer activity (IC
50
75 μM) of telmisartan (IC
50
125 μM) or ZnSO
4
(IC
50
225 μM) and did not show toxicity on non-cancer cells, inducing oxidative stress with cellular ROS generation and GSH/GSSG decrease. Apoptosis was the dominant form of cell death for the complex. The Bax/Bcl-XL ratio was significantly increased as well as caspase-3 activation. Both the complex and the ligand bind to bovine serum albumin (BSA) and can be stored and transported by the protein but the interaction with the complex is greater. Telmisartan binds BSA by hydrophobic interactions while the interaction of ZnTelm occurs through van der Waals forces and hydrogen bonding. Therefore, it can be shown that the coordination complex ZnTelm improved the anticancer activity of the antihypertensive drug telmisartan (IC
50
75 μM and 125 μM, respectively) and the interaction with BSA.
Graphical Abstract
Improvement of the anticancer activities of telmisartan by Zn(II) complexation and mechanisms of action. Intrinsic apoptotic pathway: induction ofoxidative stress and regulation of proteins related to apoptosis. The complex interacted with bovine serum albumin (BSA) and can be stored and transported by the protein. |
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ISSN: | 0163-4984 1559-0720 |
DOI: | 10.1007/s12011-019-02013-w |