Unlocking the potential of aromatase inhibitors: recent advances in drug design, synthesis, docking activity, and in vitro bioactivity evaluations

Niloufar Moharrer Navaei, Narvan Moharrer Navaei
{"title":"Unlocking the potential of aromatase inhibitors: recent advances in drug design, synthesis, docking activity, and in vitro bioactivity evaluations","authors":"Niloufar Moharrer Navaei, Narvan Moharrer Navaei","doi":"10.53063/synsint.2023.34183","DOIUrl":null,"url":null,"abstract":"Breast cancer, a global health concern claiming approximately 685,000 lives in 2020, necessitates continual advancements in therapeutic strategies. Estrogen and aromatase play pivotal roles in hormone-responsive breast cancer, with 80% of patients exhibiting estrogen receptor-positive tumors. Aromatase inhibitors (AIs), notably non-steroidal inhibitors like anastrozole and letrozole, have significantly improved outcomes, yet challenges persist, including side effects. This review focuses on recent developments in AIs, exploring xanthone derivatives, imidazole derivatives, and curcumin derivatives as potential inhibitors of aromatase. Molecular docking studies, employing Auto Dock and other tools, reveal the binding affinities and interactions of these compounds with the aromatase enzyme. Among xanthones, Erythrommone emerges as a potent inhibitor, holding promise for clinical trials. Imidazole derivatives, synthesized through the Debus-Radziszewski reaction, demonstrate anticancer potential, with compounds like 1a exhibiting superior efficacy against MCF7 cells. ADME-Tox analyses indicate promising drug-likeness but reveal potential mutagenic effects and environmental impacts. Curcumin derivatives, particularly 1,5-diaryl-1,4-pentadien-3-ones, present alternatives to address curcumin's bioavailability challenges. A study of 25 compounds (DKC) identifies DKC-10 as a potent inhibitor, outperforming established breast cancer drugs in terms of binding affinity and interactions with aromatase and ERα+ receptors. These findings underscore the importance of exploring diverse chemical structures in developing AIs, paving the way for more effective and well-tolerated therapeutics. The integration of computational techniques, such as molecular docking studies, accelerates drug discovery by predicting interactions at the molecular level. Overall, this comprehensive review provides valuable insights into the evolving landscape of aromatase inhibitors, offering a roadmap for future research and the development of advanced breast cancer therapeutics.","PeriodicalId":22113,"journal":{"name":"Synthesis and Sintering","volume":"124 3","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2023-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Synthesis and Sintering","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.53063/synsint.2023.34183","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

Abstract

Breast cancer, a global health concern claiming approximately 685,000 lives in 2020, necessitates continual advancements in therapeutic strategies. Estrogen and aromatase play pivotal roles in hormone-responsive breast cancer, with 80% of patients exhibiting estrogen receptor-positive tumors. Aromatase inhibitors (AIs), notably non-steroidal inhibitors like anastrozole and letrozole, have significantly improved outcomes, yet challenges persist, including side effects. This review focuses on recent developments in AIs, exploring xanthone derivatives, imidazole derivatives, and curcumin derivatives as potential inhibitors of aromatase. Molecular docking studies, employing Auto Dock and other tools, reveal the binding affinities and interactions of these compounds with the aromatase enzyme. Among xanthones, Erythrommone emerges as a potent inhibitor, holding promise for clinical trials. Imidazole derivatives, synthesized through the Debus-Radziszewski reaction, demonstrate anticancer potential, with compounds like 1a exhibiting superior efficacy against MCF7 cells. ADME-Tox analyses indicate promising drug-likeness but reveal potential mutagenic effects and environmental impacts. Curcumin derivatives, particularly 1,5-diaryl-1,4-pentadien-3-ones, present alternatives to address curcumin's bioavailability challenges. A study of 25 compounds (DKC) identifies DKC-10 as a potent inhibitor, outperforming established breast cancer drugs in terms of binding affinity and interactions with aromatase and ERα+ receptors. These findings underscore the importance of exploring diverse chemical structures in developing AIs, paving the way for more effective and well-tolerated therapeutics. The integration of computational techniques, such as molecular docking studies, accelerates drug discovery by predicting interactions at the molecular level. Overall, this comprehensive review provides valuable insights into the evolving landscape of aromatase inhibitors, offering a roadmap for future research and the development of advanced breast cancer therapeutics.
发掘芳香化酶抑制剂的潜力:药物设计、合成、对接活性和体外生物活性评估的最新进展
乳腺癌是一个全球健康问题,2020年约有68.5万人因此丧生,因此必须不断改进治疗策略。雌激素和芳香化酶在激素反应性乳腺癌中起关键作用,80%的患者表现为雌激素受体阳性肿瘤。芳香酶抑制剂(AIs),特别是非甾体抑制剂,如阿那曲唑和来曲唑,已经显著改善了结果,但挑战仍然存在,包括副作用。本文综述了AIs的最新进展,探索了山酮衍生物、咪唑衍生物和姜黄素衍生物作为芳香化酶的潜在抑制剂。利用Auto Dock等工具进行分子对接研究,揭示了这些化合物与芳香酶的结合亲和力和相互作用。在山酮类药物中,红胞酮是一种有效的抑制剂,有望用于临床试验。通过Debus-Radziszewski反应合成的咪唑衍生物显示出抗癌潜力,其中1a等化合物对MCF7细胞表现出优异的疗效。ADME-Tox分析显示有希望的药物相似,但揭示潜在的诱变效应和环境影响。姜黄素衍生物,特别是1,5-二芳基-1,4-戊二烯-3- 1,提供了解决姜黄素生物利用度挑战的替代方案。一项针对25种化合物(DKC)的研究发现,DKC-10是一种有效的抑制剂,在与芳香化酶和ERα+受体的结合亲和力和相互作用方面优于现有的乳腺癌药物。这些发现强调了探索不同化学结构在开发ai中的重要性,为更有效和耐受性良好的治疗铺平了道路。计算技术的整合,如分子对接研究,通过预测分子水平上的相互作用,加速了药物的发现。总的来说,这篇全面的综述为芳香化酶抑制剂的发展前景提供了有价值的见解,为未来的研究和晚期乳腺癌治疗的发展提供了路线图。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信