An Overview on Medicinal Chemistry of Synthetic and Natural Derivatives of Cannabidiol

Morales, Paula; Reggio, Patricia H.; Jagerovic, Nadine

doi:10.3389/fphar.2017.00422

Cited by 144 publications

(132 citation statements)

References 139 publications

(164 reference statements)

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“…It has been suggested that its action may be due to a weak affinity for CB1 and CB2 receptors ( Table 2) [114]. Similarly, other CBD derivatives, such as cannabidivarin (CBDV), which is a CBD analogue of C4 -propyl (2-[(1R, 6R)-3-methyl-6-prop-1-en-2)-ylcyclohex-2-en-1-yl]-5-propylbenzene-1,3-diol), 7-hydroxy-CBD (7-OH-CBD) and the hydroxylated CBD derivative of 7-carboxylic acid (7-COOH-CBD) have poor affinities for CB1 and CB2 ( Table 2) [2]. There is no published data examining their impact on the redox balance.…”

Section: Cb1/cb2 Receptorsmentioning

confidence: 99%

“…It has been shown that another CBD derivative, cannabigerol (CBG; (2-[(2E)-3,7-dimethylocta-2, 6-dienyl]-5-pentylbenzene-1,3-diol]), a naturally open analogue of cyclohexenyl CBD, activates TRPV1 as well as 5-HT 1A ( Table 2) and has antidepressant and anti-inflammatory effects in intestinal diseases [2,72,118]. CBG may also bind to PPARγ ( Table 2) and increase its transcriptional activity [92].…”

Section: -Ht 1a and Pparγ Receptorsmentioning

confidence: 99%

“…Given the limitations in the biological activity of CBD itself and its natural derivatives and the fact that the biological properties of CBD derivatives depend on their structure, synthetic derivatives are produced that have been designed so that their structure allows direct interaction with components of the redox system or indirectly with molecular targets interacting with these components, including the cannabinoid receptors ( Table 2). The derivatives with potential antioxidant and anti-inflammatory effects include, but are not limited to, (+)-CBD derivatives, dihydrocannabidiol and tetrahydrocannabidiol derivatives, and (+)-dihydro-7-hydroxy-CBD [2]. Promising synthetic derivatives that can modulate redox balance and/or inflammation are presented below.…”

Section: Effects Of Synthetic Derivatives Of Cbd On Receptorsmentioning

confidence: 99%

“…Cannabinoids are chemical derivatives of dibenzopyrene or monoterpenoid, and to date over four hundred have been identified. The most important of these are ∆ 9 -tetrahydrocannabinol (∆ 9 -THC), ∆ 8 -tetrahydrocannabinol (∆ 8 -THC), cannabinol (CBN), and cannabidiol (CBD), and they are members of a large group of biologically active compounds found in Cannabis sativa L. [2]. The medical use of cannabinoids, in particular phytocannabinoids, has been one of the most interesting approaches to pharmacotherapy in recent years.…”

Section: Introductionmentioning

confidence: 99%

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Antioxidative and Anti-Inflammatory Properties of Cannabidiol

2019

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Cannabidiol (CBD) is one of the main pharmacologically active phytocannabinoids of Cannabis sativa L. CBD is non-psychoactive but exerts a number of beneficial pharmacological effects, including anti-inflammatory and antioxidant properties. The chemistry and pharmacology of CBD, as well as various molecular targets, including cannabinoid receptors and other components of the endocannabinoid system with which it interacts, have been extensively studied. In addition, preclinical and clinical studies have contributed to our understanding of the therapeutic potential of CBD for many diseases, including diseases associated with oxidative stress. Here, we review the main biological effects of CBD, and its synthetic derivatives, focusing on the cellular, antioxidant, and anti-inflammatory properties of CBD.Antioxidants 2020, 9, 21 2 of 20 Moreover, this phytocannabinoid accelerated wound healing in a diabetic rat model by protecting the endothelial growth factor (VEGF) [11]. In addition, by preventing the formation of oxidative stress in the retina neurons of diabetic animals, CBD counteracted tyrosine nitration, which can lead to glutamate accumulation and neuronal cell death [12].This review summarizes the chemical and biological effects of CBD and its natural and synthetic derivatives. Particular attention was paid to the antioxidant and anti-inflammatory effects of CBD and its derivatives, bearing in mind the possibilities of using this phytocannabinoid to protect against oxidative stress and the consequences associated with oxidative modifications of proteins and lipids. Although CBD demonstrates safety and a good side effect profile in many clinical trials [4], all of the therapeutic options for CBD discussed in this review are limited in a concentration-dependent manner. Molecular Structure of CBDCBD is a terpenophenol compound containing twenty-one carbon atoms, with the formula C 21 H 30 O 2 and a molecular weight of 314.464 g/mol (Figure 1). The chemical structure of cannabidiol, 2-[1R-3-methyl-6R-(1-methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-1, 3-benzenediol, was determined in 1963 [13]. The current IUPAC preferred terminology is 2-[(1R,6R)-3-methyl-6-prop-1-en-2-ylcyclohex-2-en-1-yl]-5-pentylbenzene-1,3-diol. Naturally occurring CBD has a (−)-CBD structure [14]. The CBD molecule contains a cyclohexene ring (A), a phenolic ring (B) and a pentyl side chain. In addition, the terpenic ring (A) and the aromatic ring (B) are located in planes that are almost perpendicular to each other [15]. There are four known CBD side chain homologs, which are methyl, n-propyl, n-butyl, and n-pentyl [16]. All known CBD forms (Table 1) have absolute trans configuration in positions 1R and 6R [16].

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Section: Cb1/cb2 Receptorsmentioning

confidence: 99%

Section: -Ht 1a and Pparγ Receptorsmentioning

confidence: 99%

Section: Effects Of Synthetic Derivatives Of Cbd On Receptorsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Antioxidative and Anti-Inflammatory Properties of Cannabidiol

2019

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“…Research involving CBD has burgeoned in recent years (Burstein, 2015;Zuardi, 2008). Concurrently, there has been a proliferation of synthetic CBD derivatives (for a list, see Morales, Reggio, & Jagerovic, 2017). The World Drug Report 2016 showed that the majority of substances reported for the first time between 2012 and 2014 were synthetic cannabinoids.…”

Section: ____________________________________________________________mentioning

confidence: 99%

Synthetic cannabinoids severely elevate amino transferase levels. Natural cannabidiol does not.

Cushing¹,

Joseph²

2018

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Abstract:Cannabidiol (CBD) is a promising and well-studied medicinal compound found in cannabis. While CBD has a favorable safety profile, the deleterious health effects of synthetic cannabinoids are well documented. The human body is not equipped with the tools needed to catabolize synthetic cannabinoids. Among the enzymes recruited to removing them from the body are Alanine Amino Transferase (ALT) and Aspartate Amino Transferase (AST). The present article is broken into one naturalistic medical observation, and two studies. Each of these is concerned with the ALT and AST levels of patients exposed to cannabinoids. The medical observation is of four patients who mistakenly consumed a dangerous synthetic cannabinoid, JWH-018. Their ALT and AST levels were recorded once. The first experimental study is of six patients that consumed a synthetic CBD derivative, H4-CBD. ALT and AST levels were recorded over 22 weeks. The second experimental study is of 184 patients that consumed natural CBD. ALT and AST levels were recorded over 6 months. Taken together, these studies demonstrate clear differences between consumption of natural CBD, and two synthetic derivatives on ALT and AST levels.

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New and Emerging Antiepileptic Drugs

Witkin

Golani

Smith

2021

Burger's Medicinal Chemistry and Drug Discovery

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This article provides the biologist, chemist, and clinician with an overview into currently existing epilepsy medicines, an appreciation of those currently in development, and a glimpse at future possibilities. The discovery and development of antiepileptic drugs with improved efficacy and side‐effect dimensions are urgently needed. We discuss various strategies for discovering new antiepileptic drugs. We then provide summary data on the mechanisms of action, efficacy, and tolerability of some of the newer third‐generation antiepileptic drugs – eslicarbazepine, brivaracetam, retigabine, lacosamide, and perampanel. Additional compounds that are currently in development for epilepsy are also reviewed. These include the novel α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptor antagonists CERC‐611 and JNJ‐55511118 that are first‐in‐class drugs blocking only those AMPA receptors associated with the auxiliary protein TAPP γ‐8. The GABA A (α2/3)‐selective compounds, KRM‐II‐81, MP‐III‐080, and PF‐06372865 hold additional promise and potential advantage over nonselective GABA A receptor modulators. The developmental status of another positive allosteric modulator of GABA A receptors, the neuroactive steroid ganaxolone, is also summarized. In addition, two mGlu2 receptor modulators, JNJ‐40411813 and LY2812223 are discussed. Finally, initial data on cannabidiol, anakinra, and padsevonil are reviewed. Literature data derived from studies on both human epileptic tissue and rodent seizure modeling were utilized to glean several compelling novel drug targets for consideration in future antiepileptic drug discovery programs. Thus, in the past decade, key advances have been made that are benefiting the epileptic patient community. The current compounds in development and new drug targets give additional promise of improved antiepileptic drugs.

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An Overview on Medicinal Chemistry of Synthetic and Natural Derivatives of Cannabidiol

Cited by 144 publications

References 139 publications

Antioxidative and Anti-Inflammatory Properties of Cannabidiol

Antioxidative and Anti-Inflammatory Properties of Cannabidiol

Synthetic cannabinoids severely elevate amino transferase levels. Natural cannabidiol does not.

New and Emerging Antiepileptic Drugs

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