University of Cape Town, Department of Chemistry, Rondebosch 7701, South Africa.
University of Cape Town, Division of Pharmacology, Department of Medicine, Observatory 7925, South Africa.
Bioorg Med Chem Lett. 2021 Dec 15;54:128442. doi: 10.1016/j.bmcl.2021.128442. Epub 2021 Nov 8.
The FDA approved drug Dronabinol was identified in a previous study applying virtual screening using the haemozoin crystal as a target against malaria parasites. The active ingredient of dronabinol is synthetic tetrahydrocannabinol (THC), which is one of the major cannabinoids from Cannabis sativa. Traditional use of cannabis for malaria fever was reported in the world's oldest pharmacopoeia, dating to around 5000 years ago. In this research we report that THC inhibits β-haematin (synthetic haemozoin) and malaria parasite growth. Due the psychoactivity of THC, CBD, the other major naturally occurring cannabinoid that lacks the off-target psychoactive effects of THC, was also tested and inhibited β-haematin but showed only a mild antimalarial activity. To evaluate whether THC inhibit haemozoin formation, we performed a cellular haem fractionation assay that indicated that is not the likely mechanism of action. For the first time, the cannabinoid chemical structure is raised as a new chemical class to be further studied for malaria treatment, aiming to overcome the undesirable psychoactive effects of THC and optimize the antimalarial effects.
在之前的一项研究中,研究人员使用血晶作为疟疾寄生虫的靶点,通过虚拟筛选发现了美国食品和药物管理局批准的药物屈大麻酚。屈大麻酚的活性成分是合成的四氢大麻酚(THC),它是大麻中的主要大麻素之一。在世界上最古老的药典中就有关于大麻治疗疟疾发热的传统用法,该药典可追溯到大约 5000 年前。在这项研究中,我们报告说,THC 抑制β-血晶(合成疟原血红素)和疟原虫的生长。由于 THC 的精神活性,我们还测试了大麻素的另一种主要天然存在的大麻素 CBD,它缺乏 THC 的非靶向精神活性作用,它也抑制β-血晶,但只显示出轻微的抗疟活性。为了评估 THC 是否抑制疟原血红素的形成,我们进行了细胞血红素分级分离测定,表明这不是可能的作用机制。首次提出大麻素的化学结构作为一个新的化学类别,以进一步研究用于疟疾治疗,旨在克服 THC 的不良精神活性作用,并优化抗疟作用。