title: Synthesis and activity of the salicylic acid ester of bakuchiol in psoriasis-surrogate keratinocytes and skin substitutes.
abstract: BACKGROUND
  Topical retinoids are effective in retarding skin ageing and restoring homeostasis in skin conditions such as psoriasis. However their adverse effects (AEs), which include irritation (retinoid dermatitis), photosensitivity and teratogenicity, limit their use and patient compliance. Development of retinoid analogues with minimal AEs would allow a broader and more compliant use.
  
  
  OBJECTIVE
  To synthesise a novel molecule, bakuchiol salicylate (bakusylan), with a modulatory gene expression profile similar to retinoids, using as reference three prescription retinoids: tretinoin, tazarotene and adapalene.
  
  
  METHODS
  We hypothesized that because bakuchiol salicylate has a structure entirely different from existing retinoids, there would be at least a partial uncoupling of AEs from the skin-normalizing activity of this retinoid. This hypothesis was tested at the transcriptional level in psoriatic cytokine-treated cultures of keratinocytes and organotypic skin substitutes, using DNA microarrays and custom PCR arrays.
  
  
  RESULTS
  Evaluation of the gene expression profile of bakuchiol salicylate revealed elimination of several components of the retinoid-like proinflammatory response and teratogenic signature, without a substantial loss of normalizing potential. A possible mechanism of action, consisting of keratinocyte desensitization to psoriatic cytokine signalling through inhibition of the signal transducer and regulator of transcription (STAT)1/3/interferon inflammatory signal transduction axis was also identified.
  
  
  CONCLUSIONS
  Bipartite materials obtained by merging two skin-active entities with specific, complementary bioactivities, such as bakuchiol and salicylic acid, may yield a new class of functional retinoids.
authors.affiliation: Sunny BioDiscovery, Inc., Santa Paula, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Ma
authors.affiliation: Department of Organic Chemistry, Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Gobis
authors.affiliation: University of Ohio, Athens, OH, USA.
authors.forename: W R
authors.initials: WR
authors.lastname: Swindell
authors.affiliation: Sytheon, Boonton, NJ, USA.
authors.forename: R
authors.initials: R
authors.lastname: Chaudhuri
authors.affiliation: Sunny BioDiscovery, Inc., Santa Paula, CA, USA.|Polish Academy of Sciences, Institute of Oceanology, Sopot, Poland.
authors.forename: R
authors.initials: R
authors.lastname: Bojanowski
authors.affiliation: Sunny BioDiscovery, Inc., Santa Paula, CA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Bojanowski
mesh_terms: D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010636:Phenols / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D016133:Polymerase Chain Reaction / Q000379:methods; D011565:Psoriasis / Q000188:drug therapy* / Q000235:genetics; D012176:Retinoids / Q000009:adverse effects; D012459:Salicylates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D017768:Skin, Artificial
chemical_list: D016207:Cytokines; D010636:Phenols; D012176:Retinoids; D012459:Salicylates; C012765:bakuchiol