{"title":"唑类衍生物:癌症治疗的前沿药物","authors":"Anuradha Mehra, Prof. Amit Mittal, Rekha Sangwan","doi":"10.1002/slct.202403294","DOIUrl":null,"url":null,"abstract":"<p>Monocyclic 5-membered heterocycles including imidazoles, thiazoles, oxazoles, and their related compounds have gained significant attention in medicinal chemistry because of their potent anticancerous activity. These small heterocyclic molecules possess versatile properties, including biological activity, absorption, distribution, metabolism, excretion, and chemical diversity that give them immense potential as anticancer agents. It is also a fact that inherent characteristic of azoles to combine with many biological molecules through hydrogen bond, stacking, and hydrophobic interaction makes them effective against almost all cancer types. In the present paper the author discusses the way which is connected with chemical structure of monocyclic azoles and their anticancer activity namely the ability of these compounds to intercalate with DNA, to inhibit some enzymes and to interfere cellular signaling pathways. Interestingly, several azole derivatives have been seen to be effective in preclinical efficacy studies as well as in clinical trials and are considered to be potent in overcoming the problem of resistance and side effects of the common anticancer agents. As the synthetic chemistry progresses, the structural system of the azoles has diversified and development in the pharmacology has become more specific. This has helped in enhancing the formation of new molecules in the azole class with improved selectivity and efficacy. Furthermore, the comprehensive review explains how computational chemistry and structure-activity relationship (SAR) approaches are applied to the design of future-generation azole compounds. In light of these facts, this article is designed to give a broad overview of the current state of monocyclic azole-based anticancer agents in an attempt to further assert its therapeutic promise and spur further attempts at infusing the said agents into the cancer therapeutics fray. 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These small heterocyclic molecules possess versatile properties, including biological activity, absorption, distribution, metabolism, excretion, and chemical diversity that give them immense potential as anticancer agents. It is also a fact that inherent characteristic of azoles to combine with many biological molecules through hydrogen bond, stacking, and hydrophobic interaction makes them effective against almost all cancer types. In the present paper the author discusses the way which is connected with chemical structure of monocyclic azoles and their anticancer activity namely the ability of these compounds to intercalate with DNA, to inhibit some enzymes and to interfere cellular signaling pathways. Interestingly, several azole derivatives have been seen to be effective in preclinical efficacy studies as well as in clinical trials and are considered to be potent in overcoming the problem of resistance and side effects of the common anticancer agents. As the synthetic chemistry progresses, the structural system of the azoles has diversified and development in the pharmacology has become more specific. This has helped in enhancing the formation of new molecules in the azole class with improved selectivity and efficacy. Furthermore, the comprehensive review explains how computational chemistry and structure-activity relationship (SAR) approaches are applied to the design of future-generation azole compounds. In light of these facts, this article is designed to give a broad overview of the current state of monocyclic azole-based anticancer agents in an attempt to further assert its therapeutic promise and spur further attempts at infusing the said agents into the cancer therapeutics fray. 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引用次数: 0
摘要
单环五元杂环(包括咪唑、噻唑、噁唑及其相关化合物)因其强大的抗癌活性而在药物化学领域备受关注。这些小杂环分子具有多种特性,包括生物活性、吸收、分布、新陈代谢、排泄和化学多样性,这些特性赋予了它们作为抗癌剂的巨大潜力。此外,唑类化合物通过氢键、堆积和疏水作用与多种生物分子结合的固有特性,使其几乎能有效对抗所有癌症类型。在本文中,作者讨论了单环唑类化合物的化学结构与其抗癌活性之间的关系,即这些化合物能够与 DNA 相互结合、抑制某些酶以及干扰细胞信号传导途径。有趣的是,有几种唑衍生物在临床前药效研究和临床试验中都很有效,被认为能有效克服常见抗癌药物的抗药性和副作用问题。随着合成化学的发展,唑类化合物的结构体系已经多样化,药理学的发展也变得更加具体。这有助于形成具有更好选择性和药效的唑类新分子。此外,这篇综述还解释了如何将计算化学和结构-活性关系(SAR)方法应用于设计下一代唑类化合物。鉴于这些事实,本文旨在概述单环唑类抗癌药的现状,以进一步证实其治疗前景,并推动将上述药物注入癌症治疗领域的进一步尝试。本研究中的发现可能有助于开发出截然不同的治疗方法,从而改进癌症的靶向治疗。
Azole Derivatives: Cutting-Edge Agents in Cancer Therapy
Monocyclic 5-membered heterocycles including imidazoles, thiazoles, oxazoles, and their related compounds have gained significant attention in medicinal chemistry because of their potent anticancerous activity. These small heterocyclic molecules possess versatile properties, including biological activity, absorption, distribution, metabolism, excretion, and chemical diversity that give them immense potential as anticancer agents. It is also a fact that inherent characteristic of azoles to combine with many biological molecules through hydrogen bond, stacking, and hydrophobic interaction makes them effective against almost all cancer types. In the present paper the author discusses the way which is connected with chemical structure of monocyclic azoles and their anticancer activity namely the ability of these compounds to intercalate with DNA, to inhibit some enzymes and to interfere cellular signaling pathways. Interestingly, several azole derivatives have been seen to be effective in preclinical efficacy studies as well as in clinical trials and are considered to be potent in overcoming the problem of resistance and side effects of the common anticancer agents. As the synthetic chemistry progresses, the structural system of the azoles has diversified and development in the pharmacology has become more specific. This has helped in enhancing the formation of new molecules in the azole class with improved selectivity and efficacy. Furthermore, the comprehensive review explains how computational chemistry and structure-activity relationship (SAR) approaches are applied to the design of future-generation azole compounds. In light of these facts, this article is designed to give a broad overview of the current state of monocyclic azole-based anticancer agents in an attempt to further assert its therapeutic promise and spur further attempts at infusing the said agents into the cancer therapeutics fray. The discoveries made in this study may allow the development the radical different therapeutic approaches, which could lead to improved and targeted treatment of cancer.
期刊介绍:
ChemistrySelect is the latest journal from ChemPubSoc Europe and Wiley-VCH. It offers researchers a quality society-owned journal in which to publish their work in all areas of chemistry. Manuscripts are evaluated by active researchers to ensure they add meaningfully to the scientific literature, and those accepted are processed quickly to ensure rapid online publication.