Synthetic Strategies for Rare Cannabinoids Derived from Cannabis sativa.

Efficient syntheses of eight key cannabinoids were established and optimized. Predominant cannabinoids such as cannabigerol (CBG-C5) and cannabidiol (CBD-C5) were prepared from olivetol via regioselective condensation. Further treatments of CBD led to Δ9-tetrahydrocannabinol (THC-C5), Δ8-iso-tetrahydrocannabinol (iso-THC-C5), and cannabinol (CBN-C5). Alternatively, a [3 + 3] annulation between olivetol and citral yielded the minor cannabinoid cannabichromene (CBC-C5), which was converted into two very rare polycycles, cannabicyclol (CBL-C5) and cannabicitran (CBT-C5), in a one-pot reaction. Finally, all eight syntheses were extended by utilizing resorcinol and two phenolic analogues, achieving a cannabinoid group with more than 30 compounds through a facile synthesis strategy.

Activity of THC, CBD, and CBN on Human ACE2 and SARS-CoV1/2 Main Protease to Understand Antiviral Defense Mechanism.

THC, CBD, and CBN were reported as promising candidates against SARS-CoV2 infection, but the mechanism of action of these three cannabinoids is not understood. This study aims to determine the mechanism of action of THC, CBD, and CBN by selecting two essential targets that directly affect the coronavirus infections as viral main proteases and human angiotensin-converting enzyme2. Tested THC and CBD presented a dual-action action against both selected targets. Only CBD acted as a potent viral main protease inhibitor at the IC50 value of 1.86 ± 0.04 µM and exhibited only moderate activity against human angiotensin-converting enzyme2 at the IC50 value of 14.65 ± 0.47 µM. THC acted as a moderate inhibitor against both viral main protease and human angiotensin-converting enzymes2 at the IC50 value of 16.23 ± 1.71 µM and 11.47 ± 3.60 µM, respectively. Here, we discuss cannabinoid-associated antiviral activity mechanisms based on in silico docking studies and in vitro receptor binding studies.

Cannabinoids as New Drug Candidates for the Treatment of Glaucoma.

Glaucoma is a blinding eye disease that affects about 70 million patients globally today. The cannabinoid receptors and the endocannabinoid system have found attention for new drug concepts. This review will analyze the potential of cannabinoids, primarily tetrahydrocannabinol, THCVS, and cannabinol, as drug candidates and the role of CB1/CB2 receptors with regard to the pathophysiology of glaucoma. The mode of action of cannabinoids as innovative drug candidates and recent formulations for topical delivery will be discussed. Cannabinoid receptors with associated TRPV channels will be evaluated for their potential as drug targets. Especially the role of the endocannabinoid system (fatty acid amide hydrolase, monoacylglycerol lipase) impacting the prostaglandin network (cyclooxygenase, PGE, PGF) and neuroprotection by inhibition of nitric oxide radical formation is in the focus of this review. Delivery systems, including recent clinical trials, will be analyzed to evaluate the potential for innovative future ophthalmological drugs.

Miniaturized free-flow electrophoresis: production, optimization, and application using 3D printing technology.

The increasing resolution of three-dimensional (3D) printing offers simplified access to, and development of, microfluidic devices with complex 3D structures. Therefore, this technology is increasingly used for rapid prototyping in laboratories and industry. Microfluidic free flow electrophoresis (µFFE) is a versatile tool to separate and concentrate different samples (such as DNA, proteins, and cells) to different outlets in a time range measured in mere tens of seconds and offers great potential for use in downstream processing, for example. However, the production of µFFE devices is usually rather elaborate. Many designs are based on chemical pretreatment or manual alignment for the setup. Especially for the separation chamber of a µFFE device, this is a crucial step which should be automatized. We have developed a smart 3D design of a µFFE to pave the way for a simpler production. This study presents (1) a robust and reproducible way to build up critical parts of a µFFE device based on high-resolution MultiJet 3D printing; (2) a simplified insertion of commercial polycarbonate membranes to segregate separation and electrode chambers; and (3) integrated, 3D-printed wells that enable a defined sample fractionation (chip-to-world interface). In proof of concept experiments both a mixture of fluorescence dyes and a mixture of amino acids were successfully separated in our 3D-printed µFFE device.