Synthesis, inhibition of NO production and antiproliferative activities of some indole derivatives

Sinicropi, Maria Stefania; Caruso, Anna; Conforti, Filomena; Marrelli, Mariangela; Kashef, Hussein El; Lancelot, Jean‐Charles; Rault, Syl­vain; Statti, Giancarlo; Menichini, Francesco

doi:10.1080/14756360802693890

Cited by 40 publications

(36 citation statements)

References 27 publications

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“…It also helps dyslipidemia and reduces all atherogenic risk indexes, even if it does not modify body weight. BCP reduces oxidative stress, by decreasing the concentration of NO and malondialdehyde (MDA), a by-product of lipid peroxidation, and by increasing the level of the endogenous antioxidant glutathione [84]. The phytocannabinoid is able to suppress mediators involved both in inflammation and atherosclerosis, such as TNF-α and NF-κB.…”

Section: β-Caryophyllene and Inflammatory Diseasesmentioning

confidence: 99%

β-Caryophyllene: A Sesquiterpene with Countless Biological Properties

et al. 2019

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β-Caryophyllene (BCP), a natural bicyclic sesquiterpene, is a selective phytocannabinoid agonist of type 2 receptors (CB2-R). It isn’t psychogenic due to the absence of an affinity to cannabinoid receptor type 1 (CB1). Among the various biological activities, BCP exerts anti-inflammatory action via inhibiting the main inflammatory mediators, such as inducible nitric oxide synthase (iNOS), Interleukin 1 beta (IL-1β), Interleukin-6 (IL-6), tumor necrosis factor-alfa (TNF-α), nuclear factor kapp a-light-chain-enhancer of activated B cells (NF-κB), cyclooxygenase 1 (COX-1), cyclooxygenase 2 (COX-2). Peroxisome proliferator-activated receptors alpha (PPAR-α) effects are also mediated by the activation of PPAR-α and PPAR-γ receptors. In detail, many studies, in vitro and in vivo, suggest that the treatment with β-caryophyllene improves the phenotype of animals used to model various inflammatory pathologies, such as nervous system diseases (Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis, stroke), atherosclerosis, and tumours (colon, breast, pancreas, lymphoma, melanoma and glioma cancer). Furthermore, pre-clinical data have highlighted that BCP is potentially useful in Streptococcus infections, osteoporosis, steatohepatitis, and exerts anticonvulsant, analgesic, myorelaxing, sedative, and antidepressive effects. BCP is non-toxic in rodents, with a Lethal dose, 50% (LD50) greater than 5000 mg/kg. Nevertheless, it inhibits various cytochrome P450 isoforms (above all, CYP3A4), which metabolise xenobiotics, leading to adverse effects, due to drug levels over therapeutic window. All the reported data have highlighted that both pharmacological and toxicological aspects need to be further investigated with clinical trials.

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Section: β-Caryophyllene and Inflammatory Diseasesmentioning

confidence: 99%

β-Caryophyllene: A Sesquiterpene with Countless Biological Properties

et al. 2019

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“…Our results indicate that they were able to inhibit NO release by LPS-treated J774A.1 macrophages. NO is a pro-inflammatory mediator released by LPS-treated macrophages, and iNOS is the main isoform involved in NO release during inflammation [ 30 , 31 ]. Interestingly, compounds 4 and 5 also significantly inhibited iNOS expression in macrophages, indicating their inhibitory effect on both the iNOS activity and expression.…”

Section: Resultsmentioning

confidence: 99%

Anti-Inflammatory, Antioxidant and Crystallographic Studies of N-Palmitoyl-ethanol Amine (PEA) Derivatives

et al. 2017

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N-Palmitoyl-ethanolamine (PEA) is an anti-inflammatory component of egg yolk that is usually employed for the prevention of respiratory apparatus virus infection and then frequently used for its efficient anti-inflammatory and analgesic effects in experimental models of visceral, neuropathic, and inflammatory diseases. Nevertheless, data of its use in animal or human therapy are still scarce and further studies are needed. Herein, we report the biological evaluation of a small library of N-palmitoyl-ethanolamine analogues or derivatives, characterized by a protected acid function (either as palmitoyl amides or hexadecyl esters), useful to decrease their hydrolysis rate in vitro and prolong their biological activity. Two of these compounds—namely phenyl-carbamic acid hexadecyl ester (4) and 2-methyl-pentadecanoic acid (4-nitro-phenyl)-amide (5)—have shown good anti-inflammatory and antioxidant properties, without affecting the viability of J774A.1 macrophages. Finally, crystals suitable for X-ray analysis of compound 4 have been obtained, and its solved crystal structure is here reported. Our outcomes may be helpful for a rational drug design based on new PEA analogues/derivatives with improved biological properties.

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“…Cells were then grown in phenol‐red‐free medium supplemented with 1 % dextran‐coated charcoal (DCC)‐treated FBS. Cells were treated with increasing concentrations (1, 5, 10, 25, 50, 100, and 500 μ m ) of each compound for 72 h. Untreated cells were supplemented with DMSO (final concentration 0.1 %) and used as a control . Cell viability was assessed using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide reagent (MTT), according to the manufacturer's protocol (Sigma–Aldrich, Milan, Italy), as previously described .…”

Section: Methodsmentioning

confidence: 99%

“…Cells were treated with increasing concentrations (1, 5, 10, 25, 50, 100, and 500 mm)o fe ach compound for 72 h. Untreated cells were supplemented with DMSO (final concentration 0.1 %) and used as ac ontrol. [45] Cell viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reagent (MTT), according to the manufacturer's protocol (Sigma-Aldrich, Milan, Italy), as previously described. [46] For each sample, mean absorbance, measured at 570 nm, was expressed as ap ercentage of the control and plotted versus drug concentration to determine the IC 50 values (i.e., drug concentrations able to decrease cell viability by 50 %w ith respect to control) for each cell line, using GraphPad Prism 5s oftware (GraphPad Inc.,S an Diego, CA, USA).…”

Section: Biologymentioning

confidence: 99%

Old Drug Scaffold, New Activity: Thalidomide‐Correlated Compounds Exert Different Effects on Breast Cancer Cell Growth and Progression

et al. 2017

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Thalidomide was first used for relief of morning sickness in pregnant women and then withdrawn from the market because of its dramatic effects on normal fetal development. Over the last decades, it has been used successfully for the treatment of several pathologies, including cancer. Many analogues with improved activity have been synthesized and tested. Herein we report some effects on the growth and progression of MCF-7 and MDA-MB-231 breast cancer cells by a small series of thalidomide-correlated compounds, which are very effective at inducing cancer cell death by triggering TNFα-mediated apoptosis. The most active compounds are able to drastically reduce the migration of breast cancer cells by regulation of the two major proteins involved in epithelial-mesenchymal transition (EMT): vimentin and E-cadherin. Moreover, these compounds diminish the intracellular biosynthesis of vascular endothelial growth factor (VEGF), which is primarily involved in the promotion of angiogenesis, sustaining tumor progression. The multiple features of these compounds that act on various key points of the tumorigenesis process make them good candidates for preclinical studies.

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Synthesis, inhibition of NO production and antiproliferative activities of some indole derivatives

Cited by 40 publications

References 27 publications

β-Caryophyllene: A Sesquiterpene with Countless Biological Properties

β-Caryophyllene: A Sesquiterpene with Countless Biological Properties

Anti-Inflammatory, Antioxidant and Crystallographic Studies of N-Palmitoyl-ethanol Amine (PEA) Derivatives

Old Drug Scaffold, New Activity: Thalidomide‐Correlated Compounds Exert Different Effects on Breast Cancer Cell Growth and Progression

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