In Silico Study, Physicochemical, and In Vitro Lipase Inhibitory Activity of α,β-Amyrenone Inclusion Complexes with Cyclodextrins

Abstract

α,β-amyrenone (ABAME) is a triterpene derivative with many biological activities; however, its potential pharmacological use is hindered by its low solubility in water. In this context, the present work aimed to develop inclusion complexes (ICs) of ABAME with γ- and β-cyclodextrins (CD), which were systematically characterized through molecular modeling studies as well as FTIR, XRD, DSC, TGA, and SEM analyses. In vitro analyses of lipase activity were performed to evaluate possible anti-obesity properties. Molecular modeling studies indicated that the CD:ABAME ICs prepared at a 2:1 molar ratio would be more stable to the complexation process than those prepared at a 1:1 molar ratio. The physicochemical characterization showed strong evidence that corroborates with the in silico results, and the formation of ICs with CD was capable of inducing changes in ABAME physicochemical properties. ICs was shown to be a stronger inhibitor of lipase activity than Orlistat and to potentiate the inhibitory effects of ABAME on porcine pancreatic enzymes. In conclusion, a new pharmaceutical preparation with potentially improved physicochemical characteristics and inhibitory activity toward lipases was developed in this study, which could prove to be a promising ingredient for future formulations.

Phytochemical characterization of Thevetia peruviana (lucky nut) bark extracts by GC-MS analysis, along with evaluation of its biological activities, and molecular docking study

“…Among all the tentative compounds α-amyrone shows significant binding affinity scores (Kcal/mol) against all the three enzymes lipoxygenase (−16.1), α-glucosidase (-13.3) and tyrosinase (−8.1). α-amyrone is a pentacyclic triterpenoid of medicinal importance including anti hyperglycemic, anti-inflammatory (significant anti-inflammatory effect on paw edema and ear edema) [ 115 , 116 ]. When the α-glucosidase inhibitory activity of former compound was compared to the standard acarbose, the findings showed inhibition rate of (96.59 % ± 0.52) at a concentration of 1.6 μg/mL, whereas the standard (acarbose) showed an inhibition rate of 51.5 % at the concentration of 60 μg/mL (Ferreira, 2017), it has also reported in literature that α-amyrone has significant antidiabetic potential in terms of α-glucosidase inhibition [ 97 ]).…”

Increase in the Antioxidant and Anti-Inflammatory Activity of Euterpe oleracea Martius Oil Complexed in β-Cyclodextrin and Hydroxypropyl-β-Cyclodextrin

“…In general, vegetable oils are hardly used by the pharmaceutical industry due to their low solubility and hydrolytic rancidity. However, cyclodextrins have emerged as an alternative capable of solving such problems due to their ability to form inclusion complexes [ 17 , 18 , 19 ]. These complexes allow: (a) increasing biological solubility, activity, and oxidative stability, (b) reducing photosensitivity and thermosensitivity, (c) masking undesirable organoleptic characteristics, (d) reducing the volatility and toxicity of some drugs, and (e) protecting the host molecule from gastrointestinal degradation [ 20 , 21 , 22 ].…”

Formulating Bioactive Terpenes

“…Amyrin triterpenes from Burseraceae breu and caryophyllene sesquiterpenes from copaiba oils ( Copaifera sp.) are resources from Amazonian biodiversity still yet to be fully developed [ 1 , 2 , 3 , 4 ].…”