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吲哚衍生物作为抗 HIV 药物的治疗潜力:小型综述。

Therapeutic Potential of Indole Derivatives as Anti-HIV Agents: A Mini-review.

机构信息

School of Chemistry and Pharmaceutical Engineering, Huanghuai University, Zhumadian, 463000, China.

Department of Chemical and Petroleum Engineering, University of Calgary, T2N 1N4 Calgary, Alberta, Canada.

出版信息

Curr Top Med Chem. 2022;22(12):993-1008. doi: 10.2174/1568026621666211012111901.

Abstract

Acquired immunodeficiency syndrome (AIDS), caused by the human immunodeficiency virus (HIV), is one of the leading causes of human deaths. The advent of different anti-HIV drugs has turned AIDS/HIV from a deadly infection to chronic and manageable disease. However, the development of multidrug-resistant viruses, along with the severe side effects of anti-HIV agents, has compromised their efficacy and limited the treatment options. Indoles, the most common frameworks in the bioactive molecules, represent attractive scaffolds for designing and developing novel drugs. Indole derivatives are potent inhibitors of HIV enzymes such as reverse transcriptase, integrase, and protease. Furthermore, some indole-based agents, like delavirdine, have already been applied in clinics or are under clinical evaluations for the treatment of AIDS/HIV, revealing that indole moiety is a useful template for the development of anti-HIV agents. This review focuses on the recent advancement in indole derivatives, including indole alkaloids, hybrids, and dimers with anti-HIV potential, covering articles published between 2010 and 2020. The chemical structures, structure-activity relationship, and mechanisms of action are also discussed.

摘要

获得性免疫缺陷综合征(AIDS),又称艾滋病,由人类免疫缺陷病毒(HIV)引起,是导致人类死亡的主要原因之一。不同抗 HIV 药物的出现,已将 AIDS/HIV 从一种致命感染转变为慢性且可控制的疾病。然而,多药耐药病毒的出现以及抗 HIV 药物的严重副作用,降低了它们的疗效并限制了治疗选择。吲哚是生物活性分子中最常见的骨架之一,代表了设计和开发新型药物的有吸引力的支架。吲哚衍生物是 HIV 酶(如逆转录酶、整合酶和蛋白酶)的有效抑制剂。此外,一些基于吲哚的药物,如依法韦仑,已应用于临床或正在进行临床评估,用于治疗 AIDS/HIV,这表明吲哚部分是开发抗 HIV 药物的有用模板。本综述重点介绍了具有抗 HIV 潜力的吲哚衍生物,包括吲哚生物碱、杂合化合物和二聚体,涵盖了 2010 年至 2020 年期间发表的文章。还讨论了它们的化学结构、构效关系和作用机制。

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