KINETICS AND MECHANISM OF QUERCETIN OXIDATION

The kinetics of quercetin oxidation in air were determined spectrophotometrically in the pH region 4 to 7 in 50% alcohol solution at 50° C. The rate at constant pH, found to be first order with respect to quercetin, exhibited pH dependence, with the rate rising with decreasing hydrogen ion concentration. Decrease in oxygen concentration was found to decelerate the reaction. Experiments using diphenyl picrylhydrazyl indicated the presence of free radicals. The mechanism of quercetin oxidation could be fitted into the model consistent with initial ionization of quercetin to its anion and its subsequent reaction with oxygen in a fast step, followed by a unimolecular decomposition to the oxidized quercetin and hydroxyl ion via a one electron transfer mechanism. The primary step in the formation of chill haze in beer appears to be the oxidation of the phenolic entity.     

Phenethylthiazolylthiourea (PETT) compounds as a new class of HIV-1 reverse transcriptase inhibitors. 2. Synthesis and further structure-activity relationship studies of PETT analogs

Phenylethylthiazolylthiourea (PETT) derivatives have been identified as a new series of non-nucleoside inhibitors of HIV-1 RT. Structure-activity relationship studies of this class of compounds resulted in the identification of N-[2-(2-pyridyl)ethyl]-N'-[2-(5-bromopyridyl)]-thiourea hydrochloride (trovirdine; LY300046.HCl) as a highly potent anti-HIV-1 agent. Trovirdine is currently in phase one clinical trials for potential use in the treatment of AIDS. Extension of these structure-activity relationship studies to identify additional compounds in this series with improved properties is ongoing. A part of this work is described here. Replacement of the two aromatic moieties of the PETT compounds by various substituted or unsubstituted heteroaromatic rings was investigated. In addition, the effects of multiple substitution in the phenyl ring were also studied. The antiviral activities were determined on wild-type and constructed mutants of HIV-1 RT and on wild-type HIV-1 and mutant viruses derived thereof, Ile100 and Cys181, in cell culture assays. Some selected compounds were determined on double-mutant viruses, HIV-1 (Ile 100/Asn103) and HIV-1 (Ile100/Cys181). A number of highly potent analogs were synthesized. These compounds displayed IC50's against wild-type RT between 0.6 and 5 nM. In cell culture, these agents inhibited wild-type HIV-1 with ED50's between 1 and 5 nM in MT-4 cells. In addition, these derivatives inhibited mutant HIV-1 RT (Ile 100) with IC50's between 20 and 50 nM and mutant HIV-1 RT (Cys 181) with IC50's between 4 and 10 nM, and in cell culture they inhibited mutant HIV-1 (Ile100) with ED50's between 9 and 100 nM and mutant HIV-1 (Cys181) with ED50's between 3 and 20 nM.     

The real problem in the study of culture.

Comments on the discussion of the difficulties that have impeded the mainstreaming of culture, ethnicity, and race in American psychology by H. Betancourt and S. R. López (see record 1993-41028-001). Solutions of increased specificity or reliance on practitioners of mainstream psychology to modify patterns are rejected as incomplete because neither solution promises more attention to ethnicity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of incest on self and social functioning: A developmental psychopathology perspective.

The effects of child sexual abuse have become a leading concern of mental health service providers. Despite an explosion of studies, one major difficulty in this research is the lack of a developmentally sensitive model for conceptualizing short- and long-term effects and continuity and discontinuity of effects over time. This article proposes a model based in the perspective of developmental psychopathology. It is argued that incest has its unique negative effects in the domains of self- and social functioning, specifically in jeopardizing self-definition and integration, self-regulatory processes, and a sense of security and trust in relationships. Studies with clinical samples indicate that diagnostic conditions associated uniquely with a history of incest reflect serious self- and social impairments. A review of the developmental literature on self- and social development summarizes each major developmental transition from infancy to middle adulthood, and the implications for the negative effects of incest on development are discussed. Finally, implications for developmentally sensitive research are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Environmental toxins and behavioral development: A new role for psychological research.

Presents a new multiple-effects model that emphasizes subtle behavioral alteration as an early sign of toxicity and as evidence that a particular chemical agent may produce long-term impairment in susceptible individuals. The permeability of the placenta to a variety of chemical agents and the special sensitivity of the fetus to some of these agents draws attention to prenatal exposure and the need for prospective longitudinal studies of affective, social, and cognitive development in exposed individuals. The multiple-effects model provides a role for the psychologist in teratological diagnosis and research since the measurement of behavioral variation has developed primarily in psychology. Limitations inherent in both experimental animal research and correlational human studies of toxic effects make it necessary for these methodologies to be used in a complementary fashion. The implications of behavioral teratology for the study of human development and the design of protective social policies are discussed. (45 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Manganese‐Promoted Regioselective Ring‐Opening of 2,3‐Epoxy Acid Derivatives: A New Route to α‐Hydroxy Acid Derivatives

A simple and general methodology directed towards the synthesis 3‐aryl‐2‐hydroxy amides, or esters with total regioselectivity from the easily available 2,3‐epoxy amides or esters, promoted by active manganese is described. Utilizing enantiopure epoxy amides as starting materials, the corresponding 3‐aryl‐2‐hydroxy amides in enantiopure form are also available. Some synthetic applications of selected examples of 3‐aryl‐2‐hydroxy carboxylic acid derivatives are shown. A mechanism has been proposed to explain this novel reaction.     

Derivation of a Retinoid X Receptor Scaffold from Peroxisome Proliferator‐Activated Receptor γ Ligand 1‐Di(1H‐indol‐3‐yl)methyl‐4‐trifluoromethylbenzene

PPARγ agonist DIM‐Ph‐4‐CF ₃ , a template for RXRα agonist (E)‐3‐[5‐di(1‐methyl‐1H‐indol‐3‐yl)methyl‐2‐thienyl] acrylic acid: DIM‐Ph‐CF₃ is reported to inhibit cancer growth independent of PPARγ and to interact with NR4A1. As both receptors dimerize with RXR, and natural PPARγ ligands activate RXR, DIM‐Ph‐4‐CF₃ was investigated as an RXR ligand. It displaces 9‐cis‐retinoic acid from RXRα but does not activate RXRα. Structure‐based direct design led to an RXRα agonist.

     

Diabetes Mellitus and Cardiovascular Diseases: Nutraceutical Interventions Related to Caloric Restriction

Type 2 diabetes (T2DM) and cardiovascular disease (CVD) are closely associated and represent a key public health problem worldwide. An excess of adipose tissue, NAFLD, and gut dysbiosis establish a vicious circle that leads to chronic inflammation and oxidative stress. Caloric restriction (CR) is the most promising nutritional approach capable of improving cardiometabolic health. However, adherence to CR represents a barrier to patients and is the primary cause of therapeutic failure. To overcome this problem, many different nutraceutical strategies have been designed. Based on several data that have shown that CR action is mediated by AMPK/SIRT1 activation, several nutraceutical compounds capable of activating AMPK/SIRT1 signaling have been identified. In this review, we summarize recent data on the possible role of berberine, resveratrol, quercetin, and L-carnitine as CR-related nutrients. Additionally, we discuss the limitations related to the use of these nutrients in the management of T2DM and CVD.