{"title":"探索潜在的非甾体芳香化酶抑制剂治疗雌激素依赖性乳腺癌的应用。","authors":"Khushboo Pandey, Kiran Bharat Lokhande, Achintya Saha, Arvind Goja, K Venkateswara Swamy, Shuchi Nagar","doi":"10.2174/1573409919666230112170025","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Breast cancer is one of the most commonly diagnosed cancer types among women worldwide. Cytochrome P450 aromatase (CYP19A1) is an enzyme in vertebrates that selectively catalyzes the biosynthesis of estrogens from androgenic precursors. Researchers have increasingly focused on developing non-steroidal aromatase inhibitors (NSAIs) for their potential clinical use, avoiding steroidal side effects.</p><p><strong>Objectives: </strong>The objective of the present work is to search for potential lead compounds from the ZINC database through various in silico approaches.</p><p><strong>Methods: </strong>In the present study, compounds from the ZINC database were initially screened through receptor independent-based pharmacophore virtual screening. These screened molecules were subjected to several assessments, such as Lipinski rule of 5, SMART filtration, ADME prediction using SwissADME and lead optimization. Molecular docking was further applied to study the interaction of the filtered compounds with the active site of aromatase. Finally, the obtained hit compounds, consequently represented to be ideal lead candidates, were escalated to the MD simulations.</p><p><strong>Results: </strong>The results indicated that the lead compounds might be potential anti-aromatase drug candidate.</p><p><strong>Conclusion: </strong>The findings provided a valuable approach in developing novel anti-aromatase inhibitors for the treatment of ER+ breast cancer.</p>","PeriodicalId":10886,"journal":{"name":"Current computer-aided drug design","volume":"19 4","pages":"243-257"},"PeriodicalIF":1.5000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Exploring Potential Non-steroidal Aromatase Inhibitors for Therapeutic Application against Estrogen-dependent Breast Cancer.\",\"authors\":\"Khushboo Pandey, Kiran Bharat Lokhande, Achintya Saha, Arvind Goja, K Venkateswara Swamy, Shuchi Nagar\",\"doi\":\"10.2174/1573409919666230112170025\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Breast cancer is one of the most commonly diagnosed cancer types among women worldwide. Cytochrome P450 aromatase (CYP19A1) is an enzyme in vertebrates that selectively catalyzes the biosynthesis of estrogens from androgenic precursors. Researchers have increasingly focused on developing non-steroidal aromatase inhibitors (NSAIs) for their potential clinical use, avoiding steroidal side effects.</p><p><strong>Objectives: </strong>The objective of the present work is to search for potential lead compounds from the ZINC database through various in silico approaches.</p><p><strong>Methods: </strong>In the present study, compounds from the ZINC database were initially screened through receptor independent-based pharmacophore virtual screening. These screened molecules were subjected to several assessments, such as Lipinski rule of 5, SMART filtration, ADME prediction using SwissADME and lead optimization. Molecular docking was further applied to study the interaction of the filtered compounds with the active site of aromatase. Finally, the obtained hit compounds, consequently represented to be ideal lead candidates, were escalated to the MD simulations.</p><p><strong>Results: </strong>The results indicated that the lead compounds might be potential anti-aromatase drug candidate.</p><p><strong>Conclusion: </strong>The findings provided a valuable approach in developing novel anti-aromatase inhibitors for the treatment of ER+ breast cancer.</p>\",\"PeriodicalId\":10886,\"journal\":{\"name\":\"Current computer-aided drug design\",\"volume\":\"19 4\",\"pages\":\"243-257\"},\"PeriodicalIF\":1.5000,\"publicationDate\":\"2023-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current computer-aided drug design\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2174/1573409919666230112170025\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current computer-aided drug design","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/1573409919666230112170025","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Exploring Potential Non-steroidal Aromatase Inhibitors for Therapeutic Application against Estrogen-dependent Breast Cancer.
Background: Breast cancer is one of the most commonly diagnosed cancer types among women worldwide. Cytochrome P450 aromatase (CYP19A1) is an enzyme in vertebrates that selectively catalyzes the biosynthesis of estrogens from androgenic precursors. Researchers have increasingly focused on developing non-steroidal aromatase inhibitors (NSAIs) for their potential clinical use, avoiding steroidal side effects.
Objectives: The objective of the present work is to search for potential lead compounds from the ZINC database through various in silico approaches.
Methods: In the present study, compounds from the ZINC database were initially screened through receptor independent-based pharmacophore virtual screening. These screened molecules were subjected to several assessments, such as Lipinski rule of 5, SMART filtration, ADME prediction using SwissADME and lead optimization. Molecular docking was further applied to study the interaction of the filtered compounds with the active site of aromatase. Finally, the obtained hit compounds, consequently represented to be ideal lead candidates, were escalated to the MD simulations.
Results: The results indicated that the lead compounds might be potential anti-aromatase drug candidate.
Conclusion: The findings provided a valuable approach in developing novel anti-aromatase inhibitors for the treatment of ER+ breast cancer.
期刊介绍：
Aims & Scope
Current Computer-Aided Drug Design aims to publish all the latest developments in drug design based on computational techniques. The field of computer-aided drug design has had extensive impact in the area of drug design.
Current Computer-Aided Drug Design is an essential journal for all medicinal chemists who wish to be kept informed and up-to-date with all the latest and important developments in computer-aided methodologies and their applications in drug discovery. Each issue contains a series of timely, in-depth reviews, original research articles and letter articles written by leaders in the field, covering a range of computational techniques for drug design, screening, ADME studies, theoretical chemistry; computational chemistry; computer and molecular graphics; molecular modeling; protein engineering; drug design; expert systems; general structure-property relationships; molecular dynamics; chemical database development and usage etc., providing excellent rationales for drug development.
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