Affiliation:
1. Faculty of Pharmacy, Department of Pharmacy, Al-Zaytoonah University of Jordan, Amman, Jordan
Abstract
Background:
Cardiovascular disease is one of the leading causes of death. Atherosclerosis
causes arterial constriction or obstruction, resulting in acute cardiovascular illness. Cholesteryl ester
transfer protein (CETP) facilitates reverse cholesterol transport. It supports the transfer of cholesteryl
ester from HDL to LDL and VLDL. Inhibition of CETP by drugs limits cardiovascular disease by
decreasing LDL and increasing HDL.
Objectives:
In this study, fourteen trifluoromethyl substituted benzene sulfonamides 6a-6g and 7a-7g
were prepared.
Methods:
The synthesized molecules were characterized using 1H-NMR, 13C-NMR, IR and HR-MS.
They were in vitro tested to estimate their CETP inhibitory activity.
Results:
In vitro biological evaluation showed that compounds 7d-7f had the highest inhibitory activity
with 100% inhibition, while the inhibition observed by compounds 6a-6g, 7a-7c and 7g ranged
from 2%-72% at 10 μM concentration. It was found that the addition of a fourth aromatic ring
significantly improved the activity, which may be due to the hydrophobic nature of CETP. Also, the
presence of ortho-chloro, meta-chloro and para-methyl substituents results in high inhibitory activity.
Conclusion:
The induced fit docking studies revealed that hydrophobic interaction guided ligand/
CETP binding interaction in addition to H-bond formation with Q199, R201, and H232. Furthermore,
pharmacophore mapping demonstrated that this series satisfies the functionalities of the current
CETP inhibitors.
Publisher
Bentham Science Publishers Ltd.
Cited by
5 articles.
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