Affiliation:
1. Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman, Jordan
2. Department of Pharmacy, Faculty of Pharmacy, Aqaba University of Technology, Aqaba, Jordan
Abstract
Abstract:
Cardiovascular disease is one of the primary causes of death. Atherosclerosis
produces artery constriction or obstruction, which can lead to a heart attack or stroke. Cholesteryl
Ester Transfer Protein (CETP) is a protein that aids in reverse cholesterol transport.
It promotes cholesteryl ester transfer from HDL to LDL and VLDL. So, inhibition of CETP
by drugs limits cardiovascular disease by decreasing LDL and increasing HDL cholesterol.
In this study, ten ortho-fluoro substituted benzenesulfonamides 6a-6j were prepared, and
their structure was fully determined using 1H NMR, 13C NMR, HR-MS, and IR. In vitro
biological evaluation showed that compound 6d has the highest inhibitory activity with
100% inhibition, while compounds 6a-6c and 6e-6j had activities ranged from 29% - 83%
at 10 μM concentration. Interestingly, para-substituted derivatives (6d, 6g, and 6j) were
observed to have greater CETP inhibitory activities than their ortho- and meta- analogues irrespective to the
nature of substituent, i.e., CH3, Cl, or NO2. Ligandfit docking experiment revealed the difference in the binding
mode among the synthesized compounds, which is reflected in their CETP inhibitory activity.
Funder
Deanship of Scientific Research and Innovation at Al-Zaytoonah University of Jordan
Publisher
Bentham Science Publishers Ltd.