Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Dražić, T; Sachdev, V; Leopold, C; Patankar, JV; Malnar, M; Hećimović, S; Levak-Frank, S; Habuš, I; Kratky, D.
Synthesis and evaluation of novel amide amino-β-lactam derivatives as cholesterol absorption inhibitors.
Bioorg Med Chem. 2015; 23(10):2353-2359
Doi: 10.1016/j.bmc.2015.03.067
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- Führende Autor*innen der Med Uni Graz
- Kratky Dagmar
- Co-Autor*innen der Med Uni Graz
- Leopold Christina
- Levak Sanja
- Sachdev Vinay
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- Abstract:
- The β-lactam cholesterol absorption inhibitor ezetimibe is so far the only representative of this class of compounds on the market today. The goal of this work was to synthesize new amide ezetimibe analogs from trans-3-amino-(3R,4R)-β-lactam and to test their cytotoxicity and activity as cholesterol absorption inhibitors. We synthesized six new amide ezetimibe analogs. All new compounds exhibited low toxicity in MDCKIIwt, hNPC1L1/MDCKII and HepG2 cell lines and showed significant inhibition of cholesterol uptake in hNPC1L1/MDCKII cells. In addition, we determined the activity of the three compounds to inhibit cholesterol absorption in vivo. Our results demonstrate that these compounds considerably reduce cholesterol concentrations in liver and small intestine of mice. Thus, our newly synthesized amide ezetimibe analogs are cholesterol absorption inhibitors in vitro and in vivo. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Anticholesteremic Agents - chemical synthesis
- Anticholesteremic Agents - pharmacology
- Azetidines - chemical synthesis
- Azetidines - pharmacology
- Biological Transport - drug effects
- Cell Survival - drug effects
- Cholesterol - metabolism
- Cholesterol - pharmacokinetics
- Dogs -
- Ezetimibe - analogs & derivatives
- Ezetimibe - chemical synthesis
- Ezetimibe - pharmacology
- Hep G2 Cells -
- Humans -
- Intestinal Absorption - drug effects
- Intestine, Small - drug effects
- Intestine, Small - metabolism
- Liver - drug effects
- Liver - metabolism
- Madin Darby Canine Kidney Cells -
- Mice -
- Structure-Activity Relationship -
- Tritium -
- beta-Lactams - chemical synthesis
- beta-Lactams - pharmacology
- Find related publications in this database (Keywords)
- beta-Lactam
- Cholesterol absorption inhibitor
- Hyperlipidemia
- Cardiovascular heart disease