New cannabidiol (CBD) derivatives: Synthesis, anti-inflammatory activity, and molecular docking

Zi, Cheng-Ting; Xie, Yin-Rong; Niu, Yun; Liu, Zhenhao; Yang, Liu; Xi, Yongkai; Li, Zhenjie; Zhang, Fengmei; Xiang, Zemin; Sheng, Jun

doi:10.1016/j.phytol.2022.08.004

Cited by 6 publications

(4 citation statements)

References 34 publications

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“…The phenolic hydroxyl groups of CBD play a critical role in bioactivities 25 and cytotoxicity. 26 In Scheme 1, phenolic derivatives 1a−5a and 1b−5b were synthesized by different halogenated alkanes in the presence of K 2 CO 3 . Microglia are CNS immunocompetent cells.…”

Section: ■ Introductionmentioning

confidence: 99%

Cannabidiol Analogue CIAC001 for the Treatment of Morphine-Induced Addiction by Targeting PKM2

et al. 2023

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Opioid addiction is a chronically relapsing disorder that causes critical public health problems. Currently, there is a lack of effective drug treatment. Herein, one cannabidiol derivative, CIAC001, was discovered as an effective agent for treating morphine-induced addiction. In vitro, CIAC001 exhibited significantly improved anti-neuroinflammatory activity with lower toxicity. In vivo, CIAC001 ameliorated the morphine-induced withdrawal reaction, behavioral sensitization, and conditional position preference by inhibiting morphine-induced microglia activation and neuroinflammation. Target fishing for CIAC001 by activity-based protein profiling led to the identification of pyruvate kinase M2 (PKM2) as the target protein. CIAC001 bound to the protein−protein interface of the PKM2 dimer and promoted the tetramerization of PKM2. Moreover, CIAC001 exhibited an anti-neuroinflammatory effect by reversing the decrease of the PKM2 tetramer and inhibiting the nuclear translocation of PKM2. In summary, this study identified CIAC001 as a lead compound in targeting PKM2 to treat morphine-induced addiction.

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Section: ■ Introductionmentioning

confidence: 99%

Cannabidiol Analogue CIAC001 for the Treatment of Morphine-Induced Addiction by Targeting PKM2

et al. 2023

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“…Especially, several works have shown that CBD has a low affinity for classic targets, such as cannabinoid receptor type 1, 2 (CB1, CB2), despite acting as an antagonist/inverse agonist in them [17][18][19][20], so they identify potential targets, such as non-endocannabinoid G protein-coupled receptor 3, 55, 6 (GPR3, GPR55, GPR6), transient receptor potential vanilloid type 1 (TRPV1), and peroxisome proliferatoractivated receptors (PPARs), and indicate the pharmacological role of CBD on targets in vitro, and in vivo [13,[21][22][23][24]. The second approach was generating CBD analogs that increase affinities on targets, have a wide range of anti-inflammatory activities, and optimize their properties [25][26][27]. CBD analogs were generated experimentally, and most of their biological properties and activities are indicated in vitro.…”

Section: Introductionmentioning

confidence: 99%

An In Silico Study for Expanding the Utility of Cannabidiol in Alzheimer’s Disease Therapeutic Development

Choi,

Lee,

Kim

2023

IJMS

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Cannabidiol (CBD), a major non-psychoactive component of the cannabis plant, has shown therapeutic potential in Alzheimer’s disease (AD). In this study, we identified potential CBD targets associated with AD using a drug-target binding affinity prediction model and generated CBD analogs using a genetic algorithm combined with a molecular docking system. As a result, we identified six targets associated with AD: Endothelial NOS (ENOS), Myeloperoxidase (MPO), Apolipoprotein E (APOE), Amyloid-beta precursor protein (APP), Disintegrin and metalloproteinase domain-containing protein 10 (ADAM10), and Presenilin-1 (PSEN1). Furthermore, we generated CBD analogs for each target that optimize for all desired drug-likeness properties and physicochemical property filters, resulting in improved pIC50 values and docking scores compared to CBD. Molecular dynamics (MD) simulations were applied to analyze each target’s CBD and highest-scoring CBD analogs. The MD simulations revealed that the complexes of ENOS, MPO, and ADAM10 with CBD exhibited high conformational stability, and the APP and PSEN1 complexes with CBD analogs demonstrated even higher conformational stability and lower interaction energy compared to APP and PSEN1 complexes with CBD. These findings demonstrated the capable binding of the six identified targets with CBD and the enhanced binding stability achieved with the developed CBD analogs for each target.

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“…http://dx.doi.org/10.20402/ajbc.2023.0068 2002; Mechoulam et al, 2007;Burstein, 2015;Sangiovanni et al, 2019;Zi et al, 2022). 대마로부터 CBD를 포함하여 칸나비노 이드를 추출하는 방법 중 이산화탄소를 이용한 초임계유체 추출방법 (supercritical fluid extraction, SFE)은 기존의 유기용매 기반 추출 방법에 비해 선택적 추출, 짧은 시간, 낮은 운영 비용 및 환경 친화적 인 강점이 있어 점점 더 많은 관심을 받고 있다 (Qamar et al, 2021).…”

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Anti-inflammatory Evaluation of Cannabidiol from Cannabis sativa L. Obtained Using Supercritical Fluid Extraction and Cannabidiol Extract-based Cream

Kim,

et al. 2024

Asian J Beauty Cosmetol

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Purpose: This study evaluated the anti-inflammatory properties of a cannabidiol (CBD) extract obtained by supercritical fluid extraction (SFE) from Cannabis sativa L. and a cream containing the extract. Methods: The CBD extract was quantitatively analyzed using high-performance liquid chromatography. We used a lipopolysaccharide (LPS)-induced RAW 264.7 cell model of inflammation to determine the anti-inflammatory effect of the CBD extract by measuring nitric oxide (NO) production. We evaluated the anti-inflammatory properties of a cream containing the CBD extract by measuring interleukin-1 alpha (IL-1α) levels induced by sodium dodecyl sulfate (SDS) in KeraSkinTM, a human skin model. The cytotoxicity of the CBD and CBD-containing cream was assessed by MTT assay in each model. Results: The average purity of the CBD extracted and refined by SFE was 99.40%. The CBD extract and CBD cream showed concentration-dependent inhibition of inflammation. At 4 μg/mL, NO production in the RAW 264.7 cell model was significantly decreased by 64.98% compared with the negative control. IL-1α production induced by SDS in the KeraSkinTM model decreased by 54.17% in the group treated with cream containing 0.4% CBD compared with the negative control and 22.09% compared with the positive control groups. Conclusion: The medicinal use of CBD is attracting interest in Korea. Our study confirmed its exceptional anti-inflammatory properties and effectiveness in a cream product. Should additional research confirm its safety and efficacy, CBD is expected to replace existing anti-inflammatory ingredients.

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New cannabidiol (CBD) derivatives: Synthesis, anti-inflammatory activity, and molecular docking

Cited by 6 publications

References 34 publications

Cannabidiol Analogue CIAC001 for the Treatment of Morphine-Induced Addiction by Targeting PKM2

Cannabidiol Analogue CIAC001 for the Treatment of Morphine-Induced Addiction by Targeting PKM2

An In Silico Study for Expanding the Utility of Cannabidiol in Alzheimer’s Disease Therapeutic Development

Anti-inflammatory Evaluation of Cannabidiol from Cannabis sativa L. Obtained Using Supercritical Fluid Extraction and Cannabidiol Extract-based Cream

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