Jassas Rabab S, Naeem Nafeesa, Sadiq Amina, Mehmood Rabia, Alenazi Noof A, Al-Rooqi Munirah M, Mughal Ehsan Ullah, Alsantali Reem I, Ahmed Saleh A
Department of Chemistry, Jamoum University College, Umm Al-Qura University Makkah 21955 Saudi Arabia.
Department of Chemistry, University of Gujrat Gujrat 50700 Pakistan
RSC Adv. 2023 Jun 1;13(24):16413-16452. doi: 10.1039/d3ra01888a. eCollection 2023 May 30.
Heterocycles are a class of compounds that have been found to be potent inhibitors of alkaline phosphatase (AP), an enzyme that plays a critical role in various physiological processes such as bone metabolism, cell growth and differentiation, and has been linked to several diseases such as cancer and osteoporosis. AP is a widely distributed enzyme, and its inhibition has been considered as a therapeutic strategy for the treatment of these diseases. Heterocyclic compounds have been found to inhibit AP by binding to the active site of the enzyme, thereby inhibiting its activity. Heterocyclic compounds such as imidazoles, pyrazoles, and pyridines have been found to be potent AP inhibitors and have been studied as potential therapeutics for the treatment of cancer, osteoporosis, and other diseases. However, the development of more potent and selective inhibitors that can be used as therapeutics for the treatment of various diseases is an ongoing area of research. Additionally, the study of the mechanism of action of heterocyclic AP inhibitors is an ongoing area of research, which could lead to the identification of new targets and new therapeutic strategies. The enzyme known as AP has various physiological functions and is present in multiple tissues and organs throughout the body. This article presents an overview of the different types of AP isoforms, their distribution, and physiological roles. It also discusses the structure and mechanism of AP, including the hydrolysis of phosphate groups. Furthermore, the importance of AP as a clinical marker for liver disease, bone disorders, and cancer is emphasized, as well as its use in the diagnosis of rare inherited disorders such as hypophosphatasia. The potential therapeutic applications of AP inhibitors for different diseases are also explored. The objective of this literature review is to examine the function of alkaline phosphatase in various physiological conditions and diseases, as well as analyze the structure-activity relationships of recently reported inhibitors. The present review summarizes the structure-activity relationship (SAR) of various heterocyclic compounds as AP inhibitors. The SAR studies of these compounds have revealed that the presence of a heterocyclic ring, particularly a pyridine, pyrimidine, or pyrazole ring, in the molecule is essential for inhibitory activity. Additionally, the substitution pattern and stereochemistry of the heterocyclic ring also play a crucial role in determining the potency of the inhibitor.
杂环化合物是一类已被发现的强效碱性磷酸酶(AP)抑制剂。碱性磷酸酶是一种在多种生理过程中发挥关键作用的酶,如骨代谢、细胞生长和分化,并且与多种疾病如癌症和骨质疏松症有关。AP是一种广泛分布的酶,对其抑制作用已被视为治疗这些疾病的一种治疗策略。已发现杂环化合物通过与该酶的活性位点结合来抑制AP,从而抑制其活性。已发现咪唑、吡唑和吡啶等杂环化合物是强效的AP抑制剂,并已作为治疗癌症、骨质疏松症和其他疾病的潜在疗法进行研究。然而,开发更有效、更具选择性的可用于治疗各种疾病的抑制剂仍是一个正在进行的研究领域。此外,对杂环AP抑制剂作用机制的研究也是一个正在进行的研究领域,这可能会导致新靶点和新治疗策略的发现。被称为AP的这种酶具有多种生理功能,存在于全身多个组织和器官中。本文概述了不同类型的AP同工型、它们的分布和生理作用。还讨论了AP的结构和机制,包括磷酸基团的水解。此外,强调了AP作为肝病、骨疾病和癌症临床标志物的重要性,以及其在诊断罕见遗传性疾病如低磷酸酯酶症中的应用。还探讨了AP抑制剂对不同疾病的潜在治疗应用。这篇文献综述的目的是研究碱性磷酸酶在各种生理状况和疾病中的功能,以及分析最近报道的抑制剂的构效关系。本综述总结了各种杂环化合物作为AP抑制剂的构效关系(SAR)。这些化合物的SAR研究表明,分子中杂环的存在,特别是吡啶、嘧啶或吡唑环,对抑制活性至关重要。此外,杂环的取代模式和立体化学在决定抑制剂的效力方面也起着关键作用。