Naslov
Synthesis and evaluation of novel amide amino-β-lactam derivatives as cholesterol absorption inhibitors

Autori
Dražić, Tonko ; Sachdev, Vinay ; Leopold, Christina ; Patankar, Jay V. ; Malnar, Martina ; Hećimović, Silva ; Levak-Frank, Sanja ; Habuš, Ivan ; Kratky, Dagmar

Izvornik
Bioorganic & medicinal chemistry (0968-0896) 23 (2015), 10; 2353-2359

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
β-Lactam; Cholesterol absorption inhibitor; Hyperlipidemia; Cardiovascular heart disease

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA