Hierarchical Virtual Screening of Potential New Antibiotics from Polyoxygenated Dibenzofurans against Strains.

is a microorganism with high morbidity and mortality due to antibiotic-resistant strains, making the search for new therapeutic options urgent. In this context, computational drug design can facilitate the drug discovery process, optimizing time and resources. In this work, computational methods involving ligand- and structure-based virtual screening were employed to identify potential antibacterial agents against the MRSA and VRSA strains.

Identification of New Rofecoxib-Based Cyclooxygenase-2 Inhibitors: A Bioinformatics Approach.

The cyclooxygenase-2 receptor is a therapeutic target for planning potential drugs with anti-inflammatory activity. The selective cyclooxygenase-2 (COX-2) inhibitor rofecoxib was selected as a pivot molecule to perform virtual ligand-based screening from six commercial databases. We performed the search for similarly shaped Rapid Overlay of Chemical Structures (ROCS) and electrostatic (EON) compounds.

The 3-phenylcoumarin derivative 6,7-dihydroxy-3-[3',4'-methylenedioxyphenyl]-coumarin downmodulates the FcγR- and CR-mediated oxidative metabolism and elastase release in human neutrophils: Possible mechanisms underlying inhibition of the formation and release of neutrophil extracellular traps.

In this study, we report the ability of a set of eight 3-phenylcoumarin derivatives bearing 6,7- or 5,7-dihydroxyl groups, free or acetylated, bound to the benzopyrone moiety, to modulate the effector functions of human neutrophils. In general, (i) 6,7-disubstituted compounds (5, 6, 19, 20) downmodulated the Fcγ receptor-mediated neutrophil oxidative metabolism more strongly than 5,7-disubstituted compounds (21, 22, 23, 24), and (ii) hydroxylated compounds (5, 19, 21, 23) downmodulated this neutrophil function more effectively than their acetylated counterparts (6, 20, 22, 24, respectively). Compounds 5 (6,7-dihydroxy-3-[3',4'-methylenedioxyphenyl]-coumarin) and 19 (6,7-dihydroxy-3-[3',4'-dihydroxyphenyl]-coumarin) effectively downmodulated the neutrophil oxidative metabolism elicited via Fcγ and/or complement receptors.

Lapachol, a compound targeting pyrimidine metabolism, ameliorates experimental autoimmune arthritis.

Background: The inhibition of pyrimidine biosynthesis by blocking the dihydroorotate dehydrogenase (DHODH) activity, the prime target of leflunomide (LEF), has been proven to be an effective strategy for rheumatoid arthritis (RA) treatment. However, a considerable proportion of RA patients are refractory to LEF. Here, we investigated lapachol (LAP), a natural naphthoquinone, as a potential DHODH inhibitor and addressed its immunosuppressive properties.

Molecular modeling and statistical analysis in the design of derivatives of human dipeptidyl peptidase IV.

Human dipeptidyl peptidase IV (hDDP-IV) has a considerable importance in inactivation of glucagon-like peptide-1, which is related to type 2 diabetes. One approach for the treatment is the development of small hDDP-IV inhibitors. In order to design better inhibitors, we analyzed 5-(aminomethyl)-6-(2,4-dichlrophenyl)-2-(3,5-dimethoxyphenyl)pyrimidin-4-amine and a set of 24 molecules found in the BindingDB web database for model designing.

Oral Administration of Peptide-Based Drugs: Beyond Lipinski's Rule.

The use of peptides in therapy presents several limitations, from physicochemical characteristics to inadequate pharmacokinetic profiles for oral absorption. As peptides are gaining importance in the therapeutic arsenal, there is an increasing need to rationalize the main characteristics of this compound class in the market. Therefore, we performed an extensive analysis of all known peptide drugs and clinical candidates based on their peptide features, physicochemical and structural properties, and correlated these with their administration route and therapeutic classes.

Semisynthesis of new aphidicolin derivatives with high activity against Trypanosoma cruzi.

Chagas disease continues to be a difficult disease to eradicate, largely because of the widespread populations it affects as well as the highly toxic effects of current therapies. Thus, the exploration of innovative scaffolds, ideally with distinct mechanisms of action, is urgently needed. The natural product aphidicolin and its effects on cell cycle division have been widely studied; it is a potent inhibitor of parasitic cells.

[Pap smears among pregnant women in Southern Brazil: a representative cross-sectional survey].

Purpose: To determine the prevalence and risk factors associated with failure of voluntary screening for cervical cancer during the gestational period in Rio Grande, Rio Grande do Sul State, Southern Brazil.

Methods: Previously trained interviewers applied a standardized questionnaire in the maternity to all mothers from this municipality who had delivered from January 1st to December 31st 2010 to obtain information about the demographic characteristics of the pregnant women, family socioeconomic status, and prenatal care received. The χ² test was used to compare proportions and Poisson regression with robust adjustment of variance was used in the multivariate analysis.

[Prenatal care in public and private health services: a population-based survey in Rio Grande, Rio Grande do Sul State, Brazil].

This study aimed to evaluate public and private prenatal care for women in Rio Grande, Rio Grande do Sul State, Brazil. Women who gave birth at the two local maternity hospitals from January 1 to December 31, 2010, answered a standardized questionnaire. The interview sites in the public sector were primary health care units with and without the Family Health Strategy (FHS) and outpatient clinics; the private sector included clinics operated by health plans and private physicians' offices.

[Characteristics of women victims of sexual violence and their compliance with outpatient follow-up: time trends at a referral center in Campinas, São Paulo State, Brazil].

Sexual violence is a crime against individual integrity and sexual freedom. It affects women of all socioeconomic levels, and the perpetrator does not choose the victim's color or age. It is a source of high financial cost and a serious public health problem in Brazil.