Precious Ayorinde Akinnusi, Samuel Olawale Olubode, Ayomide Oluwadarasimi Adebesin, Adebowale Abiodun Alade, Victor Chinedu Nwoke, Sidiqat Adamson Shodehinde
{"title":"新型潜在的糜蛋白酶、脾脏酪氨酸激酶和前列腺素D2受体三效抑制剂治疗哮喘的最佳分子结合数据和药代动力学特征。","authors":"Precious Ayorinde Akinnusi, Samuel Olawale Olubode, Ayomide Oluwadarasimi Adebesin, Adebowale Abiodun Alade, Victor Chinedu Nwoke, Sidiqat Adamson Shodehinde","doi":"10.1186/s43141-023-00577-8","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Asthma is a chronic and complex pulmonary condition that affects the airways. A total of 250,000 asthma-related deaths are recorded annually and several proteins including chymase, spleen tyrosine kinase, and prostaglandin D2 receptor have been implicated in the pathophysiology of asthma. Different anti-inflammatory drugs have been developed for the treatment of asthma, particularly corticosteroids, but the associated adverse reactions cannot be overlooked. It is therefore of interest to identify and develop small molecule inhibitors of the integral proteins associated with asthma that have very little or no side effects. Herein, a molecular modeling approach was employed to screen the bioactive compounds in Chromolaena odorata and identify compounds with high binding affinity to the protein targets.</p><p><strong>Results: </strong>Five compounds were identified after rigorous and precise molecular screening namely (-)-epicatechin, chlorogenic acid, ombuine, quercetagetin, and quercetin 3-O-rutinoside. These compounds generally showed impressive binding to all the targets understudy. However, chlorogenic acid, quercetagetin, and quercetin 3-O-rutinoside showed better prospects in terms of triple-action inhibition. Further pulmonary and oral pharmacokinetics showed positive results for all the reported compounds. The generated pharmacophore model showed hydrogen bond donor, hydrogen bond acceptor, and aromatic rings as basic structural features required for triple action inhibition.</p><p><strong>Conclusion: </strong>These findings suggest that these compounds could be explored as triple-action inhibitors of the protein targets. They are, therefore, recommended for further analysis.</p>","PeriodicalId":74026,"journal":{"name":"Journal, genetic engineering & biotechnology","volume":"21 1","pages":"113"},"PeriodicalIF":3.6000,"publicationDate":"2023-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10638233/pdf/","citationCount":"0","resultStr":"{\"title\":\"Optimal molecular binding data and pharmacokinetic profiles of novel potential triple-action inhibitors of chymase, spleen tyrosine kinase, and prostaglandin D2 receptor in the treatment of asthma.\",\"authors\":\"Precious Ayorinde Akinnusi, Samuel Olawale Olubode, Ayomide Oluwadarasimi Adebesin, Adebowale Abiodun Alade, Victor Chinedu Nwoke, Sidiqat Adamson Shodehinde\",\"doi\":\"10.1186/s43141-023-00577-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Asthma is a chronic and complex pulmonary condition that affects the airways. A total of 250,000 asthma-related deaths are recorded annually and several proteins including chymase, spleen tyrosine kinase, and prostaglandin D2 receptor have been implicated in the pathophysiology of asthma. Different anti-inflammatory drugs have been developed for the treatment of asthma, particularly corticosteroids, but the associated adverse reactions cannot be overlooked. It is therefore of interest to identify and develop small molecule inhibitors of the integral proteins associated with asthma that have very little or no side effects. Herein, a molecular modeling approach was employed to screen the bioactive compounds in Chromolaena odorata and identify compounds with high binding affinity to the protein targets.</p><p><strong>Results: </strong>Five compounds were identified after rigorous and precise molecular screening namely (-)-epicatechin, chlorogenic acid, ombuine, quercetagetin, and quercetin 3-O-rutinoside. These compounds generally showed impressive binding to all the targets understudy. However, chlorogenic acid, quercetagetin, and quercetin 3-O-rutinoside showed better prospects in terms of triple-action inhibition. Further pulmonary and oral pharmacokinetics showed positive results for all the reported compounds. The generated pharmacophore model showed hydrogen bond donor, hydrogen bond acceptor, and aromatic rings as basic structural features required for triple action inhibition.</p><p><strong>Conclusion: </strong>These findings suggest that these compounds could be explored as triple-action inhibitors of the protein targets. They are, therefore, recommended for further analysis.</p>\",\"PeriodicalId\":74026,\"journal\":{\"name\":\"Journal, genetic engineering & biotechnology\",\"volume\":\"21 1\",\"pages\":\"113\"},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2023-11-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10638233/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal, genetic engineering & biotechnology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1186/s43141-023-00577-8\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal, genetic engineering & biotechnology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1186/s43141-023-00577-8","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
Optimal molecular binding data and pharmacokinetic profiles of novel potential triple-action inhibitors of chymase, spleen tyrosine kinase, and prostaglandin D2 receptor in the treatment of asthma.
Background: Asthma is a chronic and complex pulmonary condition that affects the airways. A total of 250,000 asthma-related deaths are recorded annually and several proteins including chymase, spleen tyrosine kinase, and prostaglandin D2 receptor have been implicated in the pathophysiology of asthma. Different anti-inflammatory drugs have been developed for the treatment of asthma, particularly corticosteroids, but the associated adverse reactions cannot be overlooked. It is therefore of interest to identify and develop small molecule inhibitors of the integral proteins associated with asthma that have very little or no side effects. Herein, a molecular modeling approach was employed to screen the bioactive compounds in Chromolaena odorata and identify compounds with high binding affinity to the protein targets.
Results: Five compounds were identified after rigorous and precise molecular screening namely (-)-epicatechin, chlorogenic acid, ombuine, quercetagetin, and quercetin 3-O-rutinoside. These compounds generally showed impressive binding to all the targets understudy. However, chlorogenic acid, quercetagetin, and quercetin 3-O-rutinoside showed better prospects in terms of triple-action inhibition. Further pulmonary and oral pharmacokinetics showed positive results for all the reported compounds. The generated pharmacophore model showed hydrogen bond donor, hydrogen bond acceptor, and aromatic rings as basic structural features required for triple action inhibition.
Conclusion: These findings suggest that these compounds could be explored as triple-action inhibitors of the protein targets. They are, therefore, recommended for further analysis.