Romanski, S. and Stamellou, E. and Jaraba, J. T. and Storz, D. and Kraemer, B. K. and Hafner, M. and Amslinger, S. and Schmalz, H. G. and Yard, B. A. (2013) Enzyme-triggered CO-releasing molecules (ET-CORMs): Evaluation of biological activity in relation to their structure. FREE RADICAL BIOLOGY AND MEDICINE, 65. pp. 78-88. ISSN 0891-5849, 1873-4596
Full text not available from this repository. (Request a copy)Abstract
Acyloxydiene-Fe(CO)(3) complexes act as enzyme-triggered CO-releasing molecules (ET-CORMs) and can deliver CO intracellularly via esterase-mediated hydrolysis. The protective properties of structurally different ET-CORMs on hypothermic preservation damage and their ability to inhibit VCAM-1 expression were tested on cultured human umbilical vein endothelial cells (HUVEC) and renal proximal tubular epithelial cells (PTEC) using a structure-activity approach. Cytotoxicity of ET-CORMs, protection against hypothermic preservation damage, and inhibition of VCAM-1 expression were assessed. Cytotoxicity of 2-cyclohexenone and 1,3-cyclohexanedione-derived ET-CORMs was more pronounced in HUVEC compared to PTEC and was dependent on the position and type of the ester (acyloxy) substituent(s) (acetate > pivalate > palmitate). Protection against hypothermic preservation injury was only observed for 2-cyclohexenone-derived ET-CORMs and was not mediated by the ET-CORM decomposition product 2-cyclohexenone itself. Structural requirements for protection by these ET-CORMs were different for HUVEC and PTEC. Protection was affected by the nature of the ester functionality in both cell lines. VCAM-1 expression was inhibited by both 2-cyclohexenone- and 1,3-cyclohexanedione-derived ET-CORMs. 2-Cyclohexenone, but not 1,3-cyclohexanedione, also inhibited VCAM-1 expression. We demonstrate that structural alterations of ET-CORMs significantly affect their biological activity. Our data also indicate that different ET-CORMs behave differently in various cell types (epithelial vs endothelial). These findings warrant further studies not only to elucidate the structure-activity relation of ET-CORMs in mechanistic terms but also to assess if structural optimization will yield ET-CORMs with restricted cell specificity. (C) 2013 Elsevier Inc. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ISCHEMIA-REPERFUSION INJURY; CARBON-MONOXIDE; ISCHEMIA/REPERFUSION INJURY; INTIMAL HYPERPLASIA; ENDOTHELIAL-CELLS; CATALYTIC IRON; PRESERVATION; TRANSPLANTATION; GRAFTS; RAT; Endothelial cells; Adhesion molecules; Inflammation; Carbon monoxide |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Chemistry and Pharmacy > Institut für Organische Chemie > Arbeitskreis Dr. Sabine Amslinger |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 24 Mar 2020 10:12 |
| Last Modified: | 06 Apr 2020 05:31 |
| URI: | https://pred.uni-regensburg.de/id/eprint/15564 |
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