Validation of the Antioxidant and Enzyme Inhibitory Potential of Selected Triterpenes Using In Vitro and In Silico Studies, and the Evaluation of Their ADMET Properties

• Published in: Molecules (Basel, Switzerland) Switzerland), 2021-10, Vol.26 (21), p.6331
• Main Authors: Mamadalieva, Nilufar Z, Youssef, Fadia S, Hussain, Hidayat, Zengin, Gokhan, Mollica, Adriano, Al Musayeib, Nawal M, Ashour, Mohamed L, Westermann, Bernhard, Wessjohann, Ludger A
• Format: Article
• Language: English
• Subjects: Acetylcholinesterase; Acids; Alzheimer's disease; Antioxidants; Antioxidants - chemistry; Antioxidants - pharmacokinetics; Antioxidants - pharmacology; Assaying; Chelating Agents - chemistry; Chelating Agents - pharmacology; Chelation; Cholinesterase Inhibitors; Cupric ions; Diabetes; enzyme inhibition; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacokinetics; Enzyme Inhibitors - pharmacology; Enzymes; Ethylenediaminetetraacetic acids; Ferrous ions; Free Radical Scavengers - chemistry; Free Radical Scavengers - pharmacokinetics; Free Radical Scavengers - pharmacology; Free radicals; Galantamine; Glucosidase; Humans; in vitro assays; inflammation; Kojic acid; Molecular Conformation; Molecular Docking Simulation; Molecular Dynamics Simulation; Molecular Structure; Oleanolic acid; Oxidative stress; Pharmacodynamics; Pharmacokinetics; Pharmacology; Phytochemicals; Protease Inhibitors; Scavenging; Structure-Activity Relationship; Sulfonic acid; Tissue Distribution; Triterpenes; Triterpenes - chemistry; Triterpenes - pharmacokinetics; Triterpenes - pharmacology; Tyrosinase; virtual screening; Xylopyranoside; α-Amylase; α-Glucosidase
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules26216331

The antioxidant and enzyme inhibitory potential of fifteen cycloartane-type triterpenes' potentials were investigated using different assays. In the phosphomolybdenum method, cycloalpioside D ( ) (4.05 mmol TEs/g) showed the highest activity. In 1,1-diphenyl-2-picrylhydrazyl (DPPH*) radical and 2,2'-azino-bis(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) cation radical scavenging assays, cycloorbicoside A-7-monoacetate ( ) (5.03 mg TE/g) and cycloorbicoside B ( ) (10.60 mg TE/g) displayed the highest activities, respectively. Oleanolic acid ( ) (51.45 mg TE/g) and 3- -β-d-xylopyranoside-(23 ,24 )-16β,23;16α,24-diepoxycycloart-25(26)-en-3β,7β-diol 7-monoacetate ( ) (13.25 mg TE/g) revealed the highest reducing power in cupric ion-reducing activity (CUPRAC) and ferric-reducing antioxidant power (FRAP) assays, respectively. In metal-chelating activity on ferrous ions, compound displayed the highest activity estimated by 41.00 mg EDTAE/g (EDTA equivalents/g). The tested triterpenes showed promising AChE and BChE inhibitory potential with 3- -β-d-xylopyranoside-(23 ,24 )-16β,23;16α,24-diepoxycycloart-25(26)-en-3β,7β-diol 2',3',4',7-tetraacetate ( ), exhibiting the highest inhibitory activity as estimated from 5.64 and 5.19 mg GALAE/g (galantamine equivalent/g), respectively. Compound displayed the most potent tyrosinase inhibitory activity (113.24 mg KAE/g (mg kojic acid equivalent/g)). Regarding α-amylase and α-glucosidase inhibition, 3- -β-d-xylopyranoside-(23 ,24 )-16β,23;16α,24-diepoxycycloart-25(26)-en-3β,7β-diol ( ) (0.55 mmol ACAE/g) and compound (25.18 mmol ACAE/g) exerted the highest activities, respectively. In silico studies focused on compounds , , and as inhibitors of tyrosinase revealed that compound displayed a good ranking score (-7.069 kcal/mole) and also that the ΔG free-binding energy was the highest among the three selected compounds. From the ADMET/TOPKAT prediction, it can be concluded that compounds and displayed the best pharmacokinetic and pharmacodynamic behavior, with considerable activity in most of the examined assays.