Carbazole Is a Naturally Occurring Inhibitor of Angiogenesis and Inflammation Isolated from Antipsoriatic Coal Tar

Abstract

Coal tar is one of the oldest and an effective treatment for psoriasis. Coal tar has been directly applied to the skin, or used in combination with UV light as part of the Goeckerman treatment. The use of coal tar has caused long-term remissions in psoriasis, but has fallen out of favor because the treatment requires hospitalization and coal tar is poorly acceptable aesthetically to patients. Thus, determining the active antipsoriatic component of coal tar is of considerable therapeutic interest. We fractionated coal tar into its components, and tested them using the SVR angiogenesis inhibitor assay. Treatment of SVR endothelial cells with coal tar fractions resulted in the isolation of a single fraction with antiangiogenic activity. The active antiangiogenic compound in coal tar is carbazole. In addition to antiangiogenic activity, carbazole inhibited the production of inflammatory IL-15 by human mononuclear cells. IL-15 is elevated in psoriasis and is thought to contribute to psoriatic inflammation. Carbazole treatment also reduced activity of inducible nitric oxide synthase (iNOS), which is proinflammatory and elevated in psoriasis. The effect of carbazole on upstream pathways in human psoriasis was determined, and carbazole was shown to inhibit signal transducer and activator of transcription (stat)3-mediated transcription, which has been shown to be relevant in human psoriasis. IL-15, iNOS, and stat3 activation require the activation of the small GTPase rac for optimal activity. Carbazole was found to inhibit rac activation as a mechanism for its inhibition of downstream inflammatory and angiogenic pathways. Given its antiangiogenic and anti-inflammatory activities, carbazole is likely a major component of the antipsoriatic activity of coal tar. Carbazole and derivatives may be useful in the therapy of human psoriasis.

CC and CXC Chemokines Patterns in Psoriasis Determined by Protein Array Method Were Influenced by Goeckerman’s Therapy

“…The abnormal hyperproliferative capacity of epidermal cells is known to be diminished by this therapy (14,20). In contrast, little is known about the influence of Goeckerman's therapy of psoriasis on angiogenic activity which is abnormal in these patients (3,5). Our study addressed whether Goeckerman's therapy influences the serum level of proangiogenic chemokines ENA-78, GRO-alpha, IL-8, MCP-1 and RANTES in children with psoriasis.…”

Synthesis of novel carbazole chalcones as radical scavenger, antimicrobial and cancer chemopreventive agents

“…This 3-formyl-9-methylcarbazole (11) on Claisen-Schimdt condensation with various aromatic and heteroaromatic acetophenones in aqueous sodium hydroxide afforded titled compound (12a-o) in good to excellent yields (Table 3, Supplementary information). All the synthesised compounds were characterised by IR, 1 H NMR, 13 C NMR, CHN analysis and MS .…”

“…IR spectra (KBr disks) were recorded using a Perkin-Elmer 237 spectrophotometer. 1 H NMR (300 MHz) and 13 C NMR (100 MHz) spectra were recorded on a Bruker Avance spectrometer using DMSO-d 6 as solvent. Mass spectra were recorded on a Shimadzu LCMS-QP 1000 EX.…”

“…Therefore, tricyclic planar carbazole chromophore is predestined for intercalation into DNA. In addition to the DNA binding, carbazole derivatives present antiproliferative effect by other mechanisms, such as inhibition of angiogenesis 13 , inhibition of cyclin-dependent kinase 4 14 , inhibition of microtubulin 15 , inhibition of check point kinase 1 16 and inhibition of topoisomerase I and II 17,18 . Carvedilol 6, an antihypertensive drug, acts as a nonspecific β-adrenergic antagonist 19 .…”

Synthesis, antimicrobial activity and cytotoxicity of some new carbazole derivatives

“…It is known that natural origin carbazoles especially for those complex carbazoles fusing with a heterocyclic fragment show well-known pharmacological activities 15,16 . Accordingly, to the present, a large number of natural and synthetic carbazole derivatives have been reported to exhibit diverse biological activities such as antituberculosis 17 , antiproliferative 14 , antibacterial 18,19 , antiviral 20 , antifungal 21,22 , antitumour 23 , anti-inflammatory 24 , antioxidant 12 and antihistaminic activities 25 .…”