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用于治疗心血管疾病的活性杂合分子开发的最新进展。

Recent advances in the development of active hybrid molecules in the treatment of cardiovascular diseases.

作者信息

Singh Harbinder, Agrawal Devendra K

机构信息

Department of Translational Research, Western University of Health Sciences, Pomona, CA, USA.

Department of Translational Research, Western University of Health Sciences, Pomona, CA, USA.

出版信息

Bioorg Med Chem. 2022 May 15;62:116706. doi: 10.1016/j.bmc.2022.116706. Epub 2022 Mar 11.

DOI:10.1016/j.bmc.2022.116706
PMID:35364524
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9018605/
Abstract

Multifactorial nature of the underlying pathophysiology of chronic disorders hinders in the effective treatment and management of many complex diseases. The conventional targeted therapies have limited applications due to highly complicated disease etiology. Cardiovascular diseases (CVDs) are the group of disorders of the heart and blood vessels. Currently, there is limited knowledge on the underlying cellular and molecular mechanisms of many of the CVDs due to their complex pathophysiology and co-morbidities. Their management with conventional medications results in failure due to adverse drug reactions and clinical specificity of solo-targeting drug therapy. Therefore, it is critical to introduce an alternative strategy to treat multi-factorial diseases. In the past few years, discovery and use of multi-targeted drug therapy with hybrid molecules have shown promising results with minimal side effects, and thus considered a most effective approach. In this review article, prominent hybrid molecules combining with different active moieties are reported to synergistically and simultaneously block different pathways involved in CVDs. Here, we provide a critical evaluation and discussion on their pharmacology with mechanistic insights and the structure activity relationship. The timely information provided in this article reveals the recent trends of molecular hybridization to the scientific community interested in CVDs and help them in designing the next generation of multi-targeting drug therapeutics.

摘要

慢性疾病潜在病理生理学的多因素性质阻碍了许多复杂疾病的有效治疗和管理。由于疾病病因高度复杂,传统的靶向治疗应用有限。心血管疾病(CVD)是心脏和血管的一组病症。目前,由于其复杂的病理生理学和合并症,对于许多心血管疾病的潜在细胞和分子机制了解有限。使用传统药物对其进行管理会因药物不良反应和单靶点药物治疗的临床特异性而导致失败。因此,引入替代策略来治疗多因素疾病至关重要。在过去几年中,使用杂合分子的多靶点药物治疗的发现和应用已显示出有前景的结果,且副作用最小,因此被认为是一种最有效的方法。在这篇综述文章中,据报道与不同活性部分结合的突出杂合分子可协同并同时阻断心血管疾病中涉及的不同途径。在此,我们对它们的药理学进行批判性评估和讨论,并给出作用机制见解和构效关系。本文提供的及时信息向对心血管疾病感兴趣的科学界揭示了分子杂交的最新趋势,并帮助他们设计下一代多靶点药物疗法。