In silico docking studies and in vitro xanthine oxidase inhibitory activity of commercially available terpenoids

Abstract

<p><strong>Objective</strong> Xanthine oxidase is a highly versatile enzyme that is widely distributed among different species. The hydroxylation of purines is catalysed by xanthine oxidase and especially the conversion of xanthine to uric acid. Xanthine oxidase inhibitors are much useful, since they possess lesser side effects compared to uricosuric and anti-inflammatory agents.<strong> </strong>The present study deals with <em>in silico </em>and<em> in vitro</em> xanthine oxidase inhibitory analysis of commercially available terpenoids (bisabolol, β-caryophyllene, limonene, and α- terpinene). <strong>Methods</strong> Molecular docking studies were performed using AutoDock 4.2 and <em>in vitro</em> xanthine oxidase inhibitory activity was carried out using xanthine as the substrate. In addition, enzyme kinetics was performed using Lineweaver Burkplot analysis. Allopurinol, a known xanthine oxidase inhibitor was used as the standard. <strong>Results</strong> The results revealed that bisabolol exhibited a lowest binding energy value of about -7.33 kcal/mol. All other compounds showed binding energy values ranging between -7.33 to -5.87 kcal/mol which was less than the standard (-4.78 kcal/mol). In the xanthine oxidase assay, IC₅₀ value of bisabolol was found to be 34.70 µg/ml, whereas that of allopurinol was 8.48 µg/ml. All the remaining compounds exhibited IC₅₀ values ranging between 34.70 to 68.45 µg/ml. In the enzyme kinetic studies, bisabolol, β-caryophyllene showed non competitive and Limonene, α- terpinene and allopurinol showed competitive type of enzyme inhibition. <strong>Conclusion</strong> It can be concluded that terpenoids could be a promising remedy for the treatment of gout and related inflammatory disorders. Further <em>in vivo</em> studies are required to develop potential compounds with lesser side effects.</p

Anti‐acetylcholinesterase, antidiabetic, anti‐inflammatory, antityrosinase and antixanthine oxidase activities of Moroccan propolis

“…Xanthine oxidase activity was determined by measuring the formation of uric acid from xanthine. Xanthine oxidase inhibiting activity was conveniently measured with a modified assay according to Umamaheswari et al (2013). The assay mixture consisted of 100 lL of the sample, 350 lL of phosphate buffer (pH 7.5, 50 mM) and 45 lL of xanthine oxidase enzyme solution (0.4 units mL À1 in phosphate buffer, pH 7.5), which was prepared immediately before use.…”

Involvement of xanthine oxidase inhibition with the antioxidant property of nanoencapsulated Melaleuca alternifolia essential oil in fish experimentally infected with Pseudomonas aeruginosa

“…In the present study, we demonstrated for the first time that nanoparticles of TTO were able to prevent the upregulation of seric XO activity, similar to previous studies with essential oils, such as Boswellia dalzielii (Kohoude et al., ), Lavandula pubescens (Al‐Badani et al., ) and Salvia nemorosa (Bahadori et al., ). Although there are no prior data regarding the effect of TTO on XO activity, an in vitro study demonstrated that several terpenoids, including α‐terpinene (third principal compound of TTO), presented an inhibitory influence on XO activity with an IC 50 of 68.45 μg/ml (Umamaheswari et al., ). Notably, the capacity of TTO nanoparticles to prevent the increase in seric uric acid and ROS levels may be considered a consequence of enhanced seric XO activity.…”

Synthesis, Biological Evaluation and Docking Studies of Aurone Derivatives on Xanthine Oxidase Enzyme

“…Hasil kajian tersebut mendapati kumpulan hidroksil pada C-5 dan C-7 memainkan peranan penting dalam perencatan XO (Yan et al 2013). Selain itu, epikalokatekin (IC 50 = 36 μM), akakatekin (IC 50 = 27 μM), naringenin (IC 50 = 22 μM), mirisetin (IC 50 = 26 μM), daidzein (IC 50 = 23 μM) dan glisitin (IC 50 = 12 μM) turut menghalang pembentukan asid urik daripada enzim XO (Umamaheswari et al 2013). Khususnya, kedua-dua sebatian apigenin (IC 50 = 3.25 μM) dan protoapigenon 1'-o-propargil eter (IC 50 = 3.61 μM) adalah lebih aktif berbanding dengan allopurinol yang mempunyai nilai IC 50 8.72 μM (Hunyadi et al 2013).…”

“…Hasil analisis Lineweaver-Burk plot akan menentukan cara perencatan enzim oleh sebatian yang diuji. Halaju awal untuk pemeriksaan fotometri dinyatakan sebagai kadar keserapan pada 295 nm setiap 10 saat dalam asai selama 10 minit (Umamaheswari et al 2013;Chu et al 2014). Kajian kinetik ke atas sebatian 5f dan 5d mendapati mod perencatan kedua-dua sebatian ini ialah jenis campuran.…”