Molecular docking and in silico drug-likeness studies of Garcinia prainiana King bioactive compounds as pancreatic lipase inhibitors

Abstract

Garcinia prainiana King is an underutilized local fruit possessing high value in numerous therapeutic uses. Unlike other Garcinia species such as G. cambogia and G. atroviridis, the anti-obesity effect of G. prainiana has never been evaluated. Thus, in the present study, the inhibitory potential of bioactive compounds from G. prainiana towards pancreatic lipase, an enzyme involved in fat digestion that caused obesity was evaluated. A molecular docking study of eleven G. prainiana bioactive compounds against pancreatic lipase was performed followed by in silico drug-likeness prediction using the SwissADME tool. The docking study demonstrated that amentoflavone is the top compound showing the highest inhibition activity towards pancreatic lipase compared to other compounds. Two hydrogen bonds were formed between amentoflavone and two catalytic residues, Ser152 and His263 of pancreatic lipase. The formation of hydrophobic interactions with the lid residues, Ala260 and Ala259, may also contribute to the inhibitory effect of this compound. Other than amentoflavone, 4‴-methylamentoflavone and naringenin 7-o-β-D-glucuronide also exhibited high inhibition activities against pancreatic lipase by interacting with the catalytic and lid residues through hydrogen bonds. However, in the context of drug developability, naringenin 7-o-β-D-glucuronide was predicted to have a higher potential to be an oral drug candidate compared to amentoflavone and 4‴-methylamentoflavone. In conclusion, this study indicated the potential of G. prainiana compounds, particularly amentoflavone, 4‴- methylamentoflavone and naringenin 7-o-β-D-glucuronide as new pancreatic lipase inhibitors. However, naringenin 7-o-β-D-glucuronide has a higher drug-likeness potential that could serve as a drug candidate for the development of an anti-obesity agent.