合成基于大麻二酚的化合物作为 ACE2 抑制剂，具有治疗 COVID-19 的潜在应用。

Synthesis of cannabidiol-based compounds as ACE2 inhibitors with potential application in the treatment of COVID-19.

机构信息

Universidade Federal de Minas Gerais, Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Belo Horizonte, Brazil.

Universidade Federal de Minas Gerais, Departamento de Microbiologia, Instituto de Ciências Biológicas, Belo Horizonte, Brazil.

出版信息

Eur J Med Chem. 2023 Nov 15;260:115760. doi: 10.1016/j.ejmech.2023.115760. Epub 2023 Aug 28.

DOI:10.1016/j.ejmech.2023.115760

PMID:37657273

Abstract

Cannabis is a general name for plants of the genus Cannabis. Used as fiber, medicine, drug, for religious, therapeutic, and hedonistic purposes along the millenia, it is mostly known for its psychoactive properties. One of its major constituents, cannabidiol (CBD), a non-psychoactive substance, among many other biological activities, has shown potential as an anti-SARS-CoV-2 drug. In this work, three derivatives and an analogue of CBD were synthesized, and cell viability and antiviral activities were evaluated. None of the compounds showed cytotoxicity up to a maximum concentration of 100 μM and, in contrast, displayed a significant antiviral activity, superior to remdesivir and nafamostat mesylate, with IC values ranging from 9.4 to 1.9 μM. In order to search for a possible molecular target, the inhibitory activity of the compounds against ACE2 was investigated, with expressive results (IC ranging from 3.96 μM to 0.01 μM).

摘要

大麻是大麻属植物的统称。千百年来，大麻被广泛应用于纤维、药物、毒品以及宗教、治疗和享乐目的，其致幻特性最为人熟知。大麻的主要成分之一，大麻二酚（CBD），除了具有多种生物活性外，还具有作为抗 SARS-CoV-2 药物的潜力。在这项工作中，合成了 CBD 的三个衍生物和一个类似物，并评估了它们的细胞活力和抗病毒活性。这些化合物在最高浓度 100μM 以下均无细胞毒性，相反，表现出显著的抗病毒活性，优于瑞德西韦和那法莫司汀，IC 值范围为 9.4 至 1.9μM。为了寻找可能的分子靶标，还研究了化合物对 ACE2 的抑制活性，结果具有明显的抑制作用（IC 值范围为 3.96μM 至 0.01μM）。