Pancreatic lipase inhibition by papaverine: investigation by simulated molecular docking and subsequent in vitro evaluation

ABSTRACT

In order to develop safe and effective lipid lowering drug that affecting the absorption of dietary lipids. the pancreatic lipase inhibitory effect of papaverine alkaloid was probed. The investigation included molecular docking to fit papaverine into the binding site of pancreatic lipase employing optimal set of parameters succeeded in retrieving the closest model to the cocrystallized pose. Docking simulation suggested four binding modes for papaverine. The highest ranking binding mode have potential hydrophobic interactions with the key aniino acids Phe-215, Ala-178, Pro-180 and Ala-259 and potential aromatic stacking between isoquinoline ring and Phe-77 and Tyr-114. Moreover, papaverine forms strong hydrogen bonds with the key amino acid Ser-152 in the catalytic triad. Experimentally, papaverine illustrated substantial in vitro inhibitory effect against PL with IC[50] = 36.2 microg/ml [106.6 microM]