Synthesis and anti-influenza activities of novel baicalein analogs.

A series of novel flavones derivatives were synthesized based on modification of the active ingredients of a traditional Chinese medicine Scutellaria baicalensis GEORGI and screened for anti-influenza activity. The synthetic baicalein (flavone) analogs, especially with the B-rings substituted with bromine atoms, were much more potent than oseltamivir or ribavirin against H1N1 Tamiflu-resistant (H1N1 TR) virus and usually with more favorable selectivity. The most promising were 5b, 5c, 6b and 6c, all displaying an 50% effective concentration (EC50) at around 4.

In-vitro and in-vivo anti-cancer activity of a novel gemcitabine-cardiolipin conjugate.

Our objectives were to study the biological activity of a novel gemcitabine-cardiolipin conjugate (NEO6002) and compare that with gemcitabine. Cytotoxicity in vitro was determined against several gemcitabine-sensitive parental and gemcitabine-resistant cancer cell lines using the sulforhodamine B assay. The in vivo toxicity was examined by changes in body weight and hematologic indices of conventional mice.

Synthesis of cationic cardiolipin analogues.

An approach was developed to synthesize a new class of cationic cardiolipin analogues containing two quaternary ammonium groups with tetra alkyl groups retaining "glycerol" moiety, the central core of the molecule. Cationic cardiolipin analogues were modified via introduction of either two or four oxyethylene groups to enhance the solubility in polar solvents. These newly synthesized cationic cardiolipin analogues can be applied to a broad range of drug delivery systems such as transfection reagents.

Synthesis of baicalein derivatives as potential anti-aggregatory and anti-inflammatory agents.

The direct acylation of trimethoxyphenol (1) with substituted cinnamoyl chlorides followed by Fries rearrangement and cyclization afforded a practical route for the synthesis of novel baicalein derivatives 4 functionalized on the B-ring in good overall yields. In the methylthiazoletetrazolium bromide (MTT) assay, none of the synthetic polyhydroxyflavonoids were cytotoxic at concentrations up to 200 microM on lipopolysaccharide (LPS)-activated murine RAW 264.7 macrophages over 24 h, while in the same cells they significantly inhibited NO production.

Novel cationic cardiolipin analogue-based liposome for efficient DNA and small interfering RNA delivery in vitro and in vivo.

Cationic liposomes have been successfully used as an alternative approach to viral systems to deliver nucleic acids. However, high toxicity and inconsistent transfection efficiency have been associated with the currently available liposomes. Therefore, a novel cationic liposome was developed based on a synthetic cationic cardiolipin analogue (CCLA) to test the DNA transfection efficiency.

Enhanced therapeutic efficacy of a novel liposome-based formulation of SN-38 against human tumor models in SCID mice.

SN-38 is an active metabolite of CPT-11. The poor solubility of SN-38 in any pharmaceutically acceptable solvent and pH-dependent activity has limited its clinical use. Our objective was to evaluate an easy-to-use liposome-based formulation of SN-38 (LE-SN38) and compare the antitumor activity with its pro-drug CPT-11 against cancer cell lines and human xenograft tumor models.

Novel synthesis of flavonoids of Scutellaria baicalensis Georgi.

A concise and efficient total synthesis of the flavonoids baicalein, oroxylin A and wogonin was described. Intramolecular oxidative cyclization followed by demethylation of chalcone 1, readily prepared from trimethoxyphenol, afforded, depending upon the controlled conditions, baicalein or oroxylin A in excellent yields. Demethylation of 1 yielded 3, which, by oxidation with I(2)/dimethyl sulfoxide (DMSO), was readily converted to oroxylin A and wogonin after column chromatography.

Estrogen regulates a tissue-specific calpain in the anterior pituitary.

A PCR-based cDNA subtraction hybridization was performed to identify the genes stimulated by estrogen in the pituitary. A novel tissue-specific calpain (nCL-2'), previously shown to be expressed mainly in the stomach, was markedly induced in the pituitary after estrogen treatment. The 5'-flanking region of the calpain nCL-2' gene was analyzed to assess the molecular mechanism of estrogen regulation.