0000000000141412
AUTHOR
Maria Amigó
Synthesis and evaluation of diverse thio avarol derivatives as potential UVB photoprotective candidates.
Semisynthesis of 13 new thio avarol derivatives (4-16) and in vitro evaluation on the photodamage response induced by UVB irradiation are described. Their ability to inhibit NF-kappaB activation and TNF-alpha generation in HaCaT cells as well as their antioxidant capacity in human neutrophils has also been studied. Among them we have identified two monophenyl thio avarol derivatives (4-5) lacking cytotoxicity which can be considered promising UVB photoprotective agents through the potent inhibition of NF-kappaB activation with a mild antioxidant pharmacological profile.
Synthesis of potentially anti-inflammatory IPL576,092-contignasterol and IPL576,092-manoalide hybrids
The synthesis of two potentially anti-inflammatory steroidal hybrid compounds has been accomplished through a 16- and 17-step sequence, respectively, starting from commercially available androst-5-en-3β-ol-17-one. The synthetic strategies are based both on stereoselective side chains elaboration and high yielding functional group transformations.
Antipsoriatic effects of avarol-3′-thiosalicylate are mediated by inhibition of TNF-αgeneration and NF-κB activation in mouse skin
Background and purpose: Avarol is a marine sesquiterpenoid hydroquinone with anti-inflammatory and antipsoriatic properties. The aim of this study was to evaluate the in vitro and in vivo pharmacological behaviour of the derivative avarol-3′-thiosalicylate (TA) on some inflammatory parameters related to the pathogenesis of psoriasis. Experimental approach: Human neutrophils and monocytes as well as the human keratinocyte cell line HaCaT were used to study the effect of TA on oxidative stress, the arachidonic acid pathway, tumour necrosis factor-α (TNF-α) release and nuclear factor-κB (NF-κB) activation. All these parameters were also determined in vivo using the zymosan induced mouse air po…
Identification of avarol derivatives as potential antipsoriatic drugs using an in vitro model for keratinocyte growth and differentiation.
Contains fulltext : 49512schalkwijk.pdf (Publisher’s version ) (Closed access) Avarol, a marine sesquiterpenoid hydroquinone, and 14 avarol derivatives have shown interesting anti-inflammatory properties in previous studies. In this study, avarol and derivatives were evaluated in high-throughput keratinocyte culture models using cytokeratin 10 and SKALP/Elafin expression as markers for respectively normal and psoriatic differentiation. Avarol and five of its derivatives (5, 10, 13, 14 and 15) were selected for further study. Only 10, 13, 14 and 15 were able to inhibit keratinocyte cell growth. Changes in expression levels of 22 genes were assessed by quantitative real time PCR (qPCR). From …
Potential Antipsoriatic Avarol Derivatives as Antioxidants and Inhibitors of PGE2 Generation and Proliferation in the HaCaT Cell Line
The synthesis and structure-activity relationships for a series of 14 new avarol derivatives as antioxidants and inhibitors of cell proliferation and PGE(2) generation in human keratinocytes are described. Compound 6 (thiosalicylic derivative) was the most potent inhibitor of superoxide generation in human neutrophils and also potently inhibited PGE(2) generation in the human keratinocyte HaCaT cell line. Compound 7(3'-methylaminoavarone) presented the best antiproliferative profile, by the inhibition of (3)H-thymidine incorporation in HaCaT cells, with potency similar to the reference compound anthralin. None of the avarol derivatives showed any sign of cytotoxicity measured as LDH release…
Avarol inhibits TNF-a generation and NF-kB activation in human cells and in animal models
Avarol is a marine sesquiterpenoid hydroquinone with interesting pharmacological properties including anti-inflammatory and antipsoriatic effects. In the present study we evaluated the pharmacological effect of avarol on some inflammatory parameters related to the pathogenesis of psoriasis. Avarol inhibited tumor necrosis factor-alpha (TNF-alpha) generation in stimulated human monocytes (IC(50) 1 microM) and TNF-alpha-induced activation of nuclear factor-kappaB (NF-kappaB)-DNA binding in keratinocytes. In the mouse air pouch model, administration of avarol produced a dose-dependent reduction of TNF-alpha generation (ED(50) 9.2 nmol/pouch) as well as of interleukin (IL)-1beta, prostaglandin …