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.
Copyright (c) 2015 Jian-Hong Lu, Zhen Shen, Shu-Xin Zhang, Jin-Yu Zhang
This work is licensed under a Creative Commons Attribution 4.0 International License.Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).