👤 Dima Sabbah

Hyperlipidemia is considered a major risk factor for the progress of atherosclerosis. Cholesteryl ester transfer protein (CETP) facilitates the relocation of cholesterol esters from HDL to LDL. CETP inhibition produces higher HDL and lower LDL levels. Synthesis of nine benzylamino benzamides 8a-8f and 9a-9c was performed. Pharmacophore mapping showed that this scaffold endorsed CETP inhibitors features and consequently elaborated the high CETP binding affinity. Show less

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. In this study, fourteen trifluoromethyl substituted benzene sulfonamides 6a-6g and 7a-7g were prepared. The synthesized molecules were characterized using 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. 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. Show less

There is an alarming spread of cases of lipid disorders in the world that occur due to harmful lifestyle habits, hereditary risk influences, or as a result of other illnesses or medicines. Cholesteryl Ester Transfer Protein (CETP) is a 476-residue lipophilic glycoprotein that helps in the transport of cholesteryl ester and phospholipids from the atheroprotective HDL to the proatherogenic LDL and VLDL. Inhibition of CETP leads to elevation of HDL cholesterol and reduction of LDL cholesterol and triglycerides; therefore, it is considered a good target for the treatment of hyperlipidemia and its comorbidities. In this research, synthesis, characterization, molecular modeling, and biological evaluation of eight 3,5-bis(trifluoromethyl)benzylamino benzamides 9a-d and 10a-d were carried out. The synthesized molecules were characterized using These compounds offered inhibitory effectiveness ranging from 42.2% to 100% at a concentration of 10 μM. Compounds bearing unsubstituted three aromatic rings (9a) or ortho-CF This work concludes that 3,5-bis(trifluoromethyl)benzylamino benzamides can serve as a promising CETP inhibitor lead compound. Show less

Cardiovascular disease is the most common cause for mortality and morbidity in the developed world; its risk is inversely related to the high-density lipoprotein (HDL) cholesterol levels. Therefore, there is a great interest in developing new cholesteryl ester transfer protein (CETP) inhibitors capable of raising HDL as a novel approach for the prevention of cardiovascular disease. Herein, the synthesis and characterization of ten benzyl benzamides 8a-j that aim at CETP inhibition was performed. The in vitro CETP inhibition bioassay revealed that benzamide 8j had the best activity, with a percent inhibition of 82.2% at 10 μM concentration and an IC Show less