Anti-hyperlipidemic potential of natural product based labdane-pyrroles via inhibition of cholesterol and triglycerides synthesis

Hyperlipidemia is the clinical condition where blood has an increased level of lipids, such as cholesterol and triglycerides. Therefore controlling hyperlipidemia is considered to be a protective strategy to treat many associated diseases. Thus, a novel natural product derived pyrrole, and pyrazole-(E)-Labda-8(17),12-diene15,16-dial conjugates with cholesterol and triglycerides synthesis inhibition potential was designed through scaffold hopping approach and synthesized via one-pot selective cycloaddition. Amongst the tested hybrids, 3i exhibited excellent activity against triglyceride and cholesterol synthesis with the percentage inhibition of 71.73 +/- 0.78 and 68.61 +/- 1.19, which is comparable to the positive controls fenofibrate and atorvastatin, respectively. Compounds 3j and 3k also exhibited the considerable potential of promising leads. The HMG CoA reductase inhibitory activity of the compounds was consistent with that of inhibitory activity of cholesterol synthesis. Compound 3i showed the highest inhibitory potential (78.61 +/- 2.80) percentage of suppression, which was comparable to that of the positive control pravastatin (78.05 +/- 5.4). Favourably, none of the compounds showed cytotoxicity (HepG2) in the concentration ranging from 0.5 to 100 mu M.

Automated summary

In this study, a novel natural product derivative with potential for inhibiting cholesterol and triglyceride synthesis was designed and synthesized. The compound exhibited comparable activity to positive controls in suppressing triglyceride and cholesterol synthesis, with high inhibitory potential and no cytotoxicity. Thus, these compounds show promise as potential leads for treating hyperlipidemia.