Synthesis and Monoamine Oxidase Inhibitory Activity of Halogenated Flavones.

Small molecule neurotransmitters containing amines are metabolized by monoamine oxidase (MAO) in the nervous system. Monoamine oxidase inhibitors are a valuable class of drugs prescribed for the management of neurological disorders, including depression. A series of halogenated flavonoids similar to the dietary flavonoid acacetin were designed as selective MAO-B inhibitors. MAO-A and -B inhibition of 36 halogenated flavones were tested. The halogens (fluorine and chlorine) were placed at positions 5 and 7 on ring A of the flavone scaffold. All compounds were selective MAO-B inhibitors with micro- and nanomolar IC50 values. Compounds 9f, 10a-c, 11a-c, 11g,h, and 11l displayed inhibitory activity toward MAO-B with IC50 values between 16 to 74 nM. We conclude that halogenated flavonoids are promising molecules in pursuit of developing new agents for neurological disorders.

Phthalate Metabolites, Hydroxy-Polycyclic Aromatic Hydrocarbons, and Bisphenol Analogues in Bovine Urine Collected from China, India, and the United States.

Human exposure to endocrine-disrupting chemicals (EDCs) has aroused considerable public concern over the last three decades. Nevertheless, little is known with regard to the exposure of EDCs in farm animals. In this study, concentrations of 22 phthalate metabolites (PhMs), 15 hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs), and 8 bisphenols (BPs) were determined in 183 bovine urine samples collected from China, India, and the United States. The median concentrations of urinary PhMs, OH-PAHs, and BPs in bovines, collectively, were 66, 4.6, and 16 ng/mL, respectively. Mono-n-butyl phthalate (mBP; median, 14 ng/mL) and ∑4DEHP (four secondary metabolites of di(2-ethylhexyl) phthalate; 13 ng/mL) were the dominant PhMs; hydroxy-fluorene (OH-Fluo; 1.2 ng/mL) and -phenanthrene (OH-Phen; 1 ng/mL) were the dominant OH-PAHs; and 4,4'-di-hydroxydiphenylmethane (BPF; 10 ng/mL) and 2,2-bis(4-hydroxyphenyl) propane (BPA; 6.7 ng/mL) were the dominant BPs. Bovine urine samples from India and China contained the highest concentrations of PhMs and OH-PAHs, whereas those from India and the United States contained the highest concentrations of BPs. PhM and OH-PAH concentrations were significantly higher in the urine of bulls than those of cows; no such difference was found for BPs. Our findings establish baseline exposure information about three classes of EDCs in domestic farm animals.

Evaluation of Angiogenesis Assays.

Angiogenesis assays allow for the evaluation of pro- or anti-angiogenic activity of endogenous or exogenous factors (stimulus or inhibitors) through investigation of their pro-or anti- proliferative, migratory, and tube formation effects on endothelial cells. To model the process of angiogenesis and the effects of biomolecules on that process, both in vitro and in vivo methods are currently used. In general, in vitro methods monitor specific stages in the angiogenesis process and are used for early evaluations, while in vivo methods more accurately simulate the living microenvironment to provide more pertinent information. We review here the current state of angiogenesis assays as well as their mechanisms, advantages, and limitations.