Enhanced Antipsoriatic Activity of Mycophenolic Acid Against the TNF-α-Induced HaCaT Cell Proliferation by Conjugated Poloxamer Micelles.

Mycophenolic acid (MPA), an immunosuppressant drug, possesses antimicrobial, anticancer, and antipsoriatic activities. However, the use of MPA in therapeutic applications is limited to its poor oral bioavailability, low aqueous solubility, and undesired gastrointestinal side effects. Polymeric micelles are a drug delivery system that has been used to enhance the water solubility of pharmaceuticals.

Enhancement of Mycophenolate Mofetil Permeation for Topical Use by Eucalyptol and N-Methyl-2-pyrrolidone.

Mycophenolate mofetil (MMF) is a prodrug of mycophenolic acid (MPA) which can be metabolized by esterase. MMF has been approved by the United States Food and Drug Administration (USFDA) for treatment of psoriasis patient with skin symptoms. However, it remains unclear whether MMF is efficiently effective to treat skin symptoms developed from psoriasis.

Structural development of p-carborane-based potent non-secosteroidal vitamin D analogs.

Non-secosteroidal vitamin D receptor (VDR) ligands are promising candidates for many clinical applications. We recently developed novel non-secosteroidal VDR agonists based on p-carborane (an icosahedral carbon-containing boron cluster) as a hydrophobic core structure. Here, we report the design, synthesis and biological evaluation of carborane-based vitamin D analogs bearing various substituents at the diol moiety.

Design and synthesis of tetraol derivatives of 1,12-dicarba-closo-dodecaborane as non-secosteroidal vitamin D analogs.

Vitamin D receptor (VDR), a nuclear receptor for 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3, 1), is a promising target for multiple clinical applications. We recently developed non-secosteroidal VDR ligands based on a carbon-containing boron cluster, 1,12-dicarba-closo-dodecaborane (p-carborane), and examined the binding of one of them to VDR by means of crystallographic analysis. Here, we utilized that X-ray structure to design novel p-carborane-based tetraol-type vitamin D analogs, and we examined the biological activities of the synthesized compounds.

Synthesis and structure-activity relationship of p-carborane-based non-secosteroidal vitamin D analogs.

1α,25-Dihydroxyvitamin D3 [1α,25(OH)₂D₃: 1] is a specific modulator of nuclear vitamin D receptor (VDR), and novel vitamin D analogs are therapeutic candidates for multiple clinical applications. We recently developed non-secosteroidal VDR agonists bearing a p-carborane cage (a carbon-containing boron cluster) as a hydrophobic core structure. These carborane derivatives are structurally quite different from classical secosteroidal vitamin D analogs.

Conformational control of benzyl-o-carboranylbenzene derivatives and molecular encapsulation of acetone in the dynamically formed space of 1,3,5-tris(2-benzyl-o-carboran-1-yl)benzene.

A 1,3,5-substituted benzene platform has been widely used in the fields of supramolecular chemistry and molecular recognition. Here, we show that 1,3,5-tris(2-benzyl-o-carboran-1-yl)benzene 6 exhibits solvent-dependent conformation in the crystalline state. Recrystallization from dichloromethane-n-pentane gave the anti conformation 6-anti, while recrystallization from methanol-acetone gave the syn conformation 6-syn, in which the three benzyl-o-carboranyl moieties are located to one side of the central benzene ring.

Novel thyroid hormone receptor antagonists with an N-alkylated diphenylamine skeleton.

Thyroid hormones play important roles in growth, development and homeostasis, and disruption of their functions induces serious disease, so novel synthetic thyroid hormone analogues are candidates for clinical application. We designed and synthesized novel diphenylamine derivatives with a thiazolidinedione moiety as the terminal polar group as thyroid hormone receptor (TR) antagonists. Compounds bearing an appropriately sized N-alkyl group showed antagonistic activities towards both the hTRalpha1 and hTRbeta1 subtypes.

A novel melatonin derivative modulates sleep-wake cycle in rats.

The aim of this study was to evaluate, in comparison with melatonin (MLT), the effects of a novel 2-melatonin derivative, having a 2-trifluoromethyl group (MLTD) on the sleep-wake cycle in freely behaving rats. Doses of MLTD (100, 300 and 500 nmol/100 microl saline) or MLT (500 nmol/100 microl saline) replaced the i.c.