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
oleh: Nilufar Z. Mamadalieva, Fadia S. Youssef, Hidayat Hussain, Gokhan Zengin, Adriano Mollica, Nawal M. Al Musayeib, Mohamed L. Ashour, Bernhard Westermann, Ludger A. Wessjohann
| Format: | Article |
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| Diterbitkan: | MDPI AG 2021-10-01 |
Deskripsi
The antioxidant and enzyme inhibitory potential of fifteen cycloartane-type triterpenes’ potentials were investigated using different assays. In the phosphomolybdenum method, cycloalpioside D (<b>6</b>) (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 (<b>2</b>) (5.03 mg TE/g) and cycloorbicoside B (<b>10</b>) (10.60 mg TE/g) displayed the highest activities, respectively. Oleanolic acid (<b>14</b>) (51.45 mg TE/g) and 3-<i>O</i>-β-<span style="font-variant: small-caps;">d</span>-xylopyranoside-(23<i>R</i>,24<i>S</i>)-16β,23;16α,24-diepoxycycloart-25(26)-en-3β,7β-diol 7-monoacetate (<b>4</b>) (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 <b>2</b> 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-<i>O</i>-β-<span style="font-variant: small-caps;">d</span>-xylopyranoside-(23<i>R</i>,24<i>S</i>)-16β,23;16α,24-diepoxycycloart-25(26)-en-3β,7β-diol 2′,3′,4′,7-tetraacetate (<b>3</b>), exhibiting the highest inhibitory activity as estimated from 5.64 and 5.19 mg GALAE/g (galantamine equivalent/g), respectively. Compound <b>2</b> 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-<i>O</i>-β-<span style="font-variant: small-caps;">d</span>-xylopyranoside-(23<i>R</i>,24<i>S</i>)-16β,23;16α,24-diepoxycycloart-25(26)-en-3β,7β-diol (<b>5</b>) (0.55 mmol ACAE/g) and compound <b>3</b> (25.18 mmol ACAE/g) exerted the highest activities, respectively. In silico studies focused on compounds <b>2</b>, <b>6</b>, and <b>7</b> as inhibitors of tyrosinase revealed that compound <b>2</b> 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 <b>4</b> and <b>5</b> displayed the best pharmacokinetic and pharmacodynamic behavior, with considerable activity in most of the examined assays.