{"title":"Novel hybrid compounds containing 1,2,3-triazole and naphthalene subunits as xanthine oxidase inhibitors","authors":"Ayse Tan, Samir Abbas Ali Noma","doi":"10.1007/s13738-024-03061-3","DOIUrl":null,"url":null,"abstract":"<div><p>In the present study, some hybrid compounds containing 1,2,3-triazole and naphthalene subunits <b>16</b>(<b>a</b>–<b>g</b>) and <b>17</b>(<b>a</b>–<b>f</b>) were synthesized and characterized by <sup>1</sup>H, <sup>13</sup>C-NMR, FT-IR, and HR-MS analyses. The in vitro inhibitor activities on the xanthine oxidase (XO) enzyme of all the target compounds were investigated and compared with allopurinol, which is one of the most common gout drugs and inhibits the XO. The activity results show that all the target compounds have potential XO inhibitor activities. The compounds showed IC<sub>50</sub> values in the range of 0.825–2.254 μM on the XO. IC<sub>50</sub> value of allopurinol on the XO was determined to be 1.475 μM. <b>16e</b> and <b>17e</b> compounds among them exhibited the best inhibitions compared to other compounds and allopurinol. Additionally, molecular docking studies were carried out on the 3D crystallographic structure of the XO to investigate possible interactions with the active site of the XO of all compounds. According to the docking results, all the target compounds showed that the best binding energies vary in the between − 9.71 kcal.mol<sup>−1</sup> and − 11.43 kcal.mol<sup>−1</sup>. Finally, in silico ADME and toxicity properties of the compounds were investigated using the Swiss ADME, ProTox-II, and Osiris Property Explorer websites and it has been predicted that the target compounds have low toxicity profiles. Consequently, the compounds can be considered new promising inhibitors for the XO.</p></div>","PeriodicalId":676,"journal":{"name":"Journal of the Iranian Chemical Society","volume":null,"pages":null},"PeriodicalIF":2.2000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the Iranian Chemical Society","FirstCategoryId":"92","ListUrlMain":"https://link.springer.com/article/10.1007/s13738-024-03061-3","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
In the present study, some hybrid compounds containing 1,2,3-triazole and naphthalene subunits 16(a–g) and 17(a–f) were synthesized and characterized by 1H, 13C-NMR, FT-IR, and HR-MS analyses. The in vitro inhibitor activities on the xanthine oxidase (XO) enzyme of all the target compounds were investigated and compared with allopurinol, which is one of the most common gout drugs and inhibits the XO. The activity results show that all the target compounds have potential XO inhibitor activities. The compounds showed IC50 values in the range of 0.825–2.254 μM on the XO. IC50 value of allopurinol on the XO was determined to be 1.475 μM. 16e and 17e compounds among them exhibited the best inhibitions compared to other compounds and allopurinol. Additionally, molecular docking studies were carried out on the 3D crystallographic structure of the XO to investigate possible interactions with the active site of the XO of all compounds. According to the docking results, all the target compounds showed that the best binding energies vary in the between − 9.71 kcal.mol−1 and − 11.43 kcal.mol−1. Finally, in silico ADME and toxicity properties of the compounds were investigated using the Swiss ADME, ProTox-II, and Osiris Property Explorer websites and it has been predicted that the target compounds have low toxicity profiles. Consequently, the compounds can be considered new promising inhibitors for the XO.
期刊介绍:
JICS is an international journal covering general fields of chemistry. JICS welcomes high quality original papers in English dealing with experimental, theoretical and applied research related to all branches of chemistry. These include the fields of analytical, inorganic, organic and physical chemistry as well as the chemical biology area. Review articles discussing specific areas of chemistry of current chemical or biological importance are also published. JICS ensures visibility of your research results to a worldwide audience in science. You are kindly invited to submit your manuscript to the Editor-in-Chief or Regional Editor. All contributions in the form of original papers or short communications will be peer reviewed and published free of charge after acceptance.