Molecular Docking of Lipase Inhibitory Activities, Pharmacokinetics and Toxicity Prediction of Chemical Constituents from Curcuma aeruginosa Roxb Rhizome

Abstract

The prevalence of obesity continues to increase, and
this become risk factor for various diseases.
Currently, the use of appetite-reducing drugs for
obese sufferers still has uncomfortable side effects.
Curcuma aeruginosa Roxb rhizomes are thought to
have secondary metabolites having potential as
alternatives for anti-obesity. This research aimed to
determine the phytochemical components of the
Curcuma aeruginosa Roxb rhizome fractions
analyzed by GC-MS. Analysis on molecular
docking of lipase inhibitory activities,
pharmacokinetics, and toxicity prediction of those
chemical constituents were also studied. The ethanol
extract of Curcuma aeruginosa Roxb rhizomes was
separated to produce n-hexane (HF), ethyl acetate
(EAF), ethanol (EF), and the insoluble fractions
(IF). The GC-MS results showed that there were 34
compounds from the three fractions. Based on
molecular docking results, compound Labd-14-ene,
8,13-epoxy- (1); (5R,8R,9S,10R)-2-Formyl- 3hydroxy-

5-isopropenyl- 8-8-methyl (3a10)
octahydronaphtho [1,2-b] furan-9-ol (2); and 9α-D15α-Androstan-11-one

(3), the test ligand, have the
lowest binding affinities (-9.13 kcal/mol; -9.30
kcal/mol; and -9.30 kcal/mol). Respectively, better
than orlistat (-6.55 kcal/mol). Thus, the three
compounds have the potential to be developed as
anti-obesity by inhibiting the pancreatic lipase
enzyme protein. All the three compounds were
identified from EAF. The pkCMS results showed
that the three compounds were predicted to have
good pharmacokinetic profiles without any
significant toxicity effects, except for compound (2)
which showed positive in AMES toxicity and
compound (3) which showed positive in skin
sensitisation test.
KEYWORDS: Curcuma aeruginosa Roxb,
molecular docking, lipase inhibitor,
pharmacocinetics, toxicity