Mitchell Cancer Institute, University of South Alabama, 1660 SpringHill Ave., Mobile, AL 36604, USA.
College of Pharmacy and Health Sciences, Western New England University, 1215 Wilbraham Road, Springfield, MA 01119, USA.
Molecules. 2022 Mar 31;27(7):2294. doi: 10.3390/molecules27072294.
Cancer is the most devastating disease and second leading cause of death around the world. Despite scientific advancements in the diagnosis and treatment of cancer which can include targeted therapy, chemotherapy, endocrine therapy, immunotherapy, radiotherapy and surgery in some cases, cancer cells appear to outsmart and evade almost any method of treatment by developing drug resistance. Quinazolines are the most versatile, ubiquitous and privileged nitrogen bearing heterocyclic compounds with a wide array of biological and pharmacological applications. Most of the anti-cancer agents featuring quinazoline pharmacophore have shown promising therapeutic activity. Therefore, extensive research is underway to explore the potential of these privileged scaffolds. In this context, a molecular hybridization approach to develop hybrid drugs has become a popular tool in the field of drug discovery, especially after witnessing the successful results during the past decade. Histone deacetylases (HDACs) have emerged as an important anti-cancer target in the recent years given its role in cellular growth, gene regulation, and metabolism. Dual inhibitors, especially based on HDAC in particular, have become the center stage of current cancer drug development. Given the growing significance of dual HDAC inhibitors, in this review, we intend to compile the development of quinazoline based HDAC dual inhibitors as anti-cancer agents.
癌症是全球最具破坏性的疾病和第二大致死原因。尽管在癌症的诊断和治疗方面取得了科学进展，包括靶向治疗、化疗、内分泌治疗、免疫治疗、放疗和手术等，但癌症细胞似乎通过产生耐药性而变得更加聪明，能够逃避几乎任何治疗方法。喹唑啉类化合物是用途最广泛、无处不在且具有特权的含氮杂环化合物，具有广泛的生物学和药理学应用。大多数具有喹唑啉药效团的抗癌药物都显示出有希望的治疗活性。因此，正在进行广泛的研究以探索这些特权支架的潜力。在这种情况下，开发杂种药物的分子杂交方法已成为药物发现领域的一种流行工具，尤其是在过去十年见证了成功的结果之后。组蛋白去乙酰化酶 (HDAC) 在细胞生长、基因调控和代谢中发挥作用，近年来已成为一个重要的抗癌靶点。双抑制剂，特别是基于 HDAC 的双抑制剂，已成为当前癌症药物开发的中心舞台。鉴于双重 HDAC 抑制剂的重要性日益增加，在这篇综述中，我们旨在编译基于喹唑啉的 HDAC 双重抑制剂作为抗癌药物的开发情况。
