Indian Journal of Chemistry Vol. 58B, May 2019, pp. 587-593 Synthesis, molecular docking and evaluation of hypolipidemic activities of novel benzophenonecarboxamide derivatives Manal Al-Najdawi a , Bilal Al-Jaidi* b ,Qosay Al-Balas c , Haifa'aOdetallah b , Tariq Al-Qirim d , GhassanShattat e & Yusuf Al-Hiari f a Department of Pharmaceutical Sciences, Faculty of Pharmacy, Isra University, Amman, Jordan b Department of Pharmaceutical Sciences, Faculty of Pharmacy, Philadelphia University, Amman 19392, Jordan c Department of Medicinal Chemistry and Pharmacognosy, Jordan University of Science and Technology, Irbid 22110, Jordan d Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman 11733, Jordan e King Saud bin Abdulaziz University for Health Sciences, Riyadh 21589, Saudi Arabia f Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Jordan, Amman 11942, Jordan E-mail: bjaidi@philadelphia.edu.jo; bilaljeaidi77@gmail.com Received 2 April 2018; accepted (revised) 13 March 2019 Fibrates are well known hypolipidemic agents and act by activating Peroxisome Proliferator-Activated Receptors (PPAR); this family of receptors is the main regulator for fatty acid metabolism. In the present study, a total of six novel benzophenonecarboxamide derivatives (3-6, 9 and 10) have been synthesized and evaluated for their hypolipidemic activity. Interestingly, compounds 4 and 6 show promising hypolipidemic activity and lower the level of TG by 71% and LDL-C by 26% and 29% respectively. Further, molecular docking studies have been carried out to gain insight into the binding interactions of all the newly synthesized compounds inside the PPARα receptor and the results are in consonance with the biological activity. The encouraging in vivohypolipidemic activity of compounds 4 and 6 by lowering LDL-C levels as well as enhancing HDL-C indicates that these compounds can serve as promising lead compounds for further investigations for the development of novel hypolipidemic agents. Keywords: Fibrates, PPARα, in vivo, hypolipidemic, benzophenone, molecular docking Hyperlipidemia and atherosclerosis are the main underlying cause for the development of cardiovascular diseases which is recently being considered as the main leading cause of death worldwide 1 . Peroxisome proliferator-activated receptors (PPAR-α, β, δ and γ) are members of the ligand-activated nuclear receptor super family, considered as the key transcriptional regulators in fatty acids (FA) metabolism 2 . PPARs are important targets for drugs used in the treatment of atherosclerosis, dyslipidaemia, obesity, type-II diabetes, and other diseases caused by abnormal regulation of glucose and lipid metabolism. PPARs have recently drawn increased attention as a drug discovery target by regulating glucose and lipid metabolism 2 . PPAR-α primarily regulates fatty acid oxidation in addition to their role as regulators for many target genes such as apolipoprotein AI (Apo AI) 3 , apolipoprotein CIII (Apo CIII) 4 , apolipoprotein AV (Apo AV) 5 , phospholipid transfer protein (PLTP) 6 and scavenger receptor class B, type I (SR-BI) in liver 7 that are intimately involved in lipoprotein metabolism. A class of lipid-lowering drugs such as fenofibrate and gimfebrozil, specifically activate PPAR-α and decrease Triglyceride (TG) production by enhancing fatty acid oxidation in the liver and facilitates TG removal by stimulating lipoprotein lipase (LPL) production and suppressing Apo CIII production. PPAR-α activation also increases the levels of high density lipoprotein-cholesterol (HDL-C) by stimulating the production of Apo AI and AII 8 . The Figure 1 represents most commonly used Fibrates as well- known class of PPAR-α agonists currently used in practice. Fibrates lower HDL-cholesterol and TG levels by the activation of PPAR-α 5,9 . Long standing studies on these drugs have contributed to accumulation of considerable experimental data about their biological activity, stimulating an immense interest in the design of new agents toward the activation of PPAR-α for the treatment of dyslipidaemia. Earlier, we have reported a series of anthraquinone- 2-carboxamide derivatives as agonists PPAR-α receptor 10 . The encouraging in vivo hypolipidemic