Design, synthesis and biological evaluation of novel bergapten derivatives as potent lipid lowering agents
The aim of this study was to synthesize novel amide derivatives of bergapten and evaluate their lipid-lowering and triglyceride-lowering activities in mice. Amide derivatives of bergapten were synthesized by using lactone ring opening strategy in DMSO using NaOH as base followed by alkylation in presence of methyl iodide. The compounds were subjected to preliminary in vivo screening. Fenofibrate (30 mg/kg/day) was used as positive controls in this assay. The lipid lowering activity was evaluated using in vivo Triton model and Triton WR-1339 was used as positive control. Most of the synthesized analogs displayed remarkable plasma triglyceride-lowering activity. Compound 5 showed the best activity with (41%) triglyceride lowering activity. This compound also exhibited the most potent lipid lowering activity displaying 33%, 32% and 29% lowering in total cholesterol, phospholipids, and triglycerides, respectively. The other derivatives showed almost comparable activity with that of the parent molecule.
Anwar-ul-Hassan G. Novel developments from natural products in cardiovascular research. Phytother Res. 1998; 12: S66-69.
Deeg R, Ziegehorn J. Kinetic enzymatic method for automated determination of serum total cholesterol. J Clin Chem. 1983; 29: 1798.
Evans M, Rees A. The myotoxicity of statins. Curr Opin Lipidol. 2002; 13: 415-20.
La Rosa JC, He J, Vupputuri S. Effect of statins on risk of coronary disease: A meta-analysis of randomized controlled trials. J Am Med Assoc. 1999; 282: 2340-46.
Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, Abraham J, Adair T, Aggarwal R, Ahn SY et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: A systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012; 380: 2095-128.
Memon RA, Gilani AH. An update on hyperlipidemia and its management. J Pak Med Assoc. 1995; 45: 275-82.
Reddy KA, Lohray BB, Bhushan V, Reddy AS, Rao Mamidi NV, Reddy PP, Saibaba V, Reddy NJ, Suryaprakash A, Misra P, Vikramadithyan RK, Rajagopalan R. Novel antidiabetic and ypolipidemic agents. 5-Hydroxyl versus benzyloxy containing chroman derivatives. Med Chem. 1999; 42: 3265-78.
Witztum ZL. The oxidation hypothesis of atherosclerosis. Lancet 1994; 344:793-95.
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