Potent antimicrobial activity of 3-(4,5-diaryl-1H-imidazol-2-yl)-1H-indole derivatives against methicillin-resistant Staphylococcus aureus.

A new series of antimicrobial derivatives [3-(4,5-diaryl-1H-imidazol-2-yl)-1H-indole)] have been synthesized with potent activity against strains of Staphylococcus aureus, including methicillin-resistant strains (MRSA). Compound 17 [3-(4,5-bis(4-fluorophenyl)-1H-imidazol-2-yl)-5-bromo-1H-indole], the most active derivative was shown to inhibit the growth of all Gram-positive strains tested, including vancomycin resistant Enterococcus faecalis and Enterococcus faecium with no activity against Gram-negative bacteria.

A novel small molecule with potent anticancer activity inhibits cell growth by modulating intracellular labile zinc homeostasis.

ML-133 is a novel small molecule with potent antiproliferative activity, as shown in cancer cell lines and in a human colon tumor xenograft model. ML-133 reduces the concentration of intracellular labile zinc in HT-29 colon cancer cells, leading to induction of the Krüppel-like factor 4 transcription factor. Krüppel-like factor 4 displaces the positive regulator SP1 from the cyclin D1 promoter, thereby negatively regulating the expression of cyclin D1 and promoting the G(1)-S phase arrest of cell proliferation.

Liposome formulation of a novel hydrophobic aryl-imidazole compound for anti-cancer therapy.

Purpose: A cholesterol-free liposome formulation formed from mixtures of egg phosphatidylcholine (ePC) and poly (ethylene glycol) conjugated distearoylphosphatidylethanolamine (DSPE-PEG 2000) was optimized and evaluated for delivery of a novel anti-cancer agent ML220 (2-(5-bromo-1H-indol-3-yl)-1H-phenanthro [9,10-d] imidazole).

Results And Discussion: ML220 is highly lipophilic with a water solubility of 0.14 mug/ml and calculated log P of 5.

Adhesion and virulence properties of epidemic Canadian methicillin-resistant Staphylococcus aureus strain 1: identification of novel adhesion functions associated with plasmin-sensitive surface protein.

Epidemic Canadian methicillin-resistant Staphylococcus aureus strain 1 (CMRSA-1) comprises related subtypes that differ in phenotype and prevalence, with subtypes 1A, 1B, and 1D representing 1%, 71%, and 18%, respectively, of total CMRSA-1 isolates. The predominant CMRSA-1B subtype possesses a variant of the staphylococcal cassette chromosome mec, harboring pls, which encodes plasmin-sensitive surface protein (Pls). CMRSA-1B cells that express Pls exhibited poor adhesion to keratinocyte extracellular matrix.

Deoxyguanosine blocks allograft rejection of thymic epithelium but not lymphocyte infiltration and recognition.

Embryonic thymic lobes cultured in vitro in the presence of deoxyguanosine (dGuo) are accepted in fully mismatched recipients. The proposed explanation for this finding was the depletion of hematopoietic cells induced by the treatment associated with poor immunogenicity of thymic epithelium. We have recently demonstrated that embryonic tissues obtained at stages prior to hematopoietic colonization are nevertheless rejectable.