Synthesis and antimicrobial studies of novel derivatives of 4-(4-formyl-3-phenyl-1H-pyrazol-1-yl)benzoic acid as potent anti-Acinetobacter baumannii agents.

Microbial resistance to antibiotics is a global concern. The World Health Organization (WHO) has identified antimicrobial resistance as one the three greatest threats for human beings in the 21st century. Without urgent and coordinated action, the world is moving toward a post-antibiotic era, in which normal infections or minor injuries may become fatal. In an effort to find new agents, we report the synthesis and antimicrobial activities of 40 novel 1,3-diphenyl pyrazole derivatives. These compounds have shown zones of growth inhibition up to 85mm against Acinetobacter baumannii. We tested the active compounds against this Gram-negative bacterium in minimum inhibitory concentration (MIC) tests and found activity with concentration as low as 4µg/mL.

A newly synthetic chromium complex--chromium(phenylalanine)3 improves insulin responsiveness and reduces whole body glucose tolerance.

Low-molecular-weight organic chromium complexes such as chromium picolinate are often used as dietary supplements to improve insulin sensitivity and to correct dyslipidemia. However, toxicity associated with such chromium compounds has compromised their therapeutic value. The aim of this study was to evaluate the impact of a newly synthesized complex of chromium with phenylalanine, Cr(pa)3 on insulin-signaling and glucose tolerance. Cr(pa)3 was synthesized by chelating chromium(III) with D-phenylalanine ligand in aqueous solution. In mouse 3T3-adipocytes, Cr(pa)3 augmented insulin-stimulated glucose-uptake as assessed by a radioactive-glucose uptake assay. At the molecular level, Cr(pa)3 enhanced insulin-stimulated phosphorylation of Akt in a time- and concentration-dependent manner without altering the phosphorylation of insulin receptor. Oral treatment with Cr(pa)3 (150 microg/kg/d, for six weeks) in ob/ob+/+ obese mice significantly alleviated glucose tolerance compared with untreated obese mice. Unlike chromium picolinate, Cr(pa)3 does not cleave DNA under physiological reducing conditions. Collectively, these data suggest that Cr(pa)3 may represent a novel, less-toxic chromium supplement with potential therapeutic value to improve insulin sensitivity and glycemic control in type II diabetes.

Electrochemical Detection of Single-Stranded DNA Using Polymer-Modified Electrodes.

Glassy carbon electrodes modified by reductive electropolymerization of a thin film of poly[Ru(vbpy)(3)(2+)] or poly[Ru(vbpy)(3)(2+)/vba] (vbpy = 4-vinyl-4'-methyl-2,2'-bipyridine and vba = p-vinylbenzoic acid) were prepared. The Ru(III/II) couples for the polymer films were reversible in nonaqueous solution but were irreversible in aqueous media. The films modified with poly[Ru(vbpy)(3)(2+)] catalyzed the oxidation of aqueous guanosine 5'-monophosphate (GMP) and poly[G], producing a current enhancement in the Ru(III/II) couple for the polymer film. The catalysis was due both to electrostatic condensation of GMP and poly[G] to the Ru-modified surface and to more facile electron transfer to the Ru(III) centers in the polymer compared to the bare electrode. The presence of GMP in solution decreased the extent of decomposition of Ru(III). When single-stranded DNA containing multiple guanines was attached to the electrode modified with the poly[Ru(vbpy)(3)(2+)/vba] copolymer, enhancement of 8-13 &mgr;A for the Ru(III/II) couple was observed with 8 pmol of attached DNA. This degree of enhancement corresponds to a current efficiency of 65% based on a one-electron oxidation of guanine.

Overcoming cisplatin resistance using gold(III) mimics: anticancer activity of novel gold(III) polypyridyl complexes.

Gold(III) compounds have been recognized as anticancer agents due to their structural and electronic similarities with currently employed platinum(II) species. An added benefit to gold(III) agents is the ability to overcome cisplatin resistance. This work identified four gold(III) compounds, [Au(Phen)Cl(2)]PF(6), [Au(DPQ)Cl(2)]PF(6), [Au(DPPZ)Cl(2)]PF(6), and [Au(DPQC)Cl(2)]PF(6), (Phen = 1,10-phenanthroline, DPQ = dipyrido[3,2-d:2',3'-f]quinoxaline, DPPZ = dipyrido[3,2-a:2',3'-c] phenazine, DPQC = dipyrido[3,2-d:2',3'-f] cyclohexyl quinoxaline) that exhibited anticancer activity in both cisplatin sensitive and cisplatin resistant ovarian cancer cells. Two of these compounds, [Au(DPQ)Cl(2)]PF(6) (AQ) and [Au(DPPZ)Cl(2)]PF(6) (AZ), displayed exceptional anticancer activity and were the focus of more intensive mechanistic study. At the molecular level, AQ and AZ formed DNA adducts, generated free radicals, and upregulated pro-apoptotic signaling molecules (p53, caspases, PARP, death effectors). Taken together, these two novel gold(III) polypyridyl complexes exhibit potent antitumor activity in cisplatin resistant cancer cells. These activities may be mediated, in part, by the activation of apoptotic signaling.