Wavepress is a signal processing software that has a simple and friendly interface that can be used by researchers, professors and students. The program uses the wavelet transform, which is a signal processing tool, being used to handle a signal in the time-scale space. In this way, the program can be used for signal processing capable of reducing, without losing important information, the amount of information. Thus, it is possible to obtain graphs and tables to explore the results in a comprehensive and satisfying way. In this work, the main features of Wavepress are explored with applications in computational chemistry, and drug design, all examples are illustrated with graphs and tables got with Wavepress. researchers students transform tool timescale time scale space way reducing information Thus work chemistry design

Keggin heteropolyacids (HPW) supported on niobia have been considered for both homogeneous and heterogeneous catalysis due to its special features, like the strong Brönsted acidity, low volatility, high activity and high selectivity for various reactions in comparison with mineral acids. Literature reports many different preparation methods for these catalysts through the addition of HPW solutions, in either water or acid, over niobia under stirring. However not much is known about the way how HPW interacts with the support, neither how the temperature influences this interaction. In order to contribute to expand the knowledge on this field we report here a new way of preparing HPW supported catalysts over niobia calcined at 500 and 600 ºC, followed by a theoretical study meant to check the influence of the temperature increase on the adsorption behavior of the catalysts over the support. Our proposed method showed to be an efficient alternative for impregnation of HPW over niobia, while the theoretical results suggest that pseudohexagonal and orthorhombic are the most likely crystalline forms for these catalysts.

N-Myristoylation protein is catalyzed by N-myristoyltransferase (NMT), an essential target in Leishmania donovani, the causative agent of kala-azar. Four-dimensional quantitative structure-activity relationship (4D-QSAR) analysis was applied to a series of 77 Leishmania donovani NMT inhibitors. Then, three new compounds were proposed using QSAR models. In addition, molecular docking was performed to predict the binding affinities and interaction modes among the proposed compounds and the NMT active site. In silico absorption, distribution, metabolism and excretion (ADME) evaluation was performed and potential inhibitors demonstrated satisfactory pharmacokinetic properties.

Alzheimer disease (AD) is a complex disease related to multiple pathogenic mechanisms. A strategy to develop effective drugs is based on the so-called multi-target directed ligands (MTDL) by using hybrid compounds. So, in the present study, we have designed and synthesized two hybrids, containing the indanone-piperidine moiety of donepezil, a drug approved for the treatment of AD, and the lipoic acid scaffold, an antioxidant compound endowed with neuroprotective effects. One hybrid was synthesized in four steps with 42% global yield, and the other hybrid in six steps with 19% global yield. The latter hybrid displayed moderate inhibitory activity against human acetylcholinesterase (hAChE) and greater activity against human butyrylcholinesterases (hBuChE). The selectivity for hBuChE was further rationalized by theoretical study. Importantly, the second hybrid showed a good antioxidant activity, exhibiting better ability in scavenging 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals than lipoic acid.

Endosulfan is an organochlorine insecticide, widely used in insect control. Unfortunately, it is also an acute neurotoxic compound to both insects and mammals, including humans, and has been responsible for many severe poisonings and several fatal cases. Endosulfan also imitates or enhances the effect of the female hormone estrogen, having the capability of causing reproductive and developmental damage in both, animals and humans, and its exposure has been linked to liver tissue injury. This persistent lipophilic compound is one of the most abundant organochlorine pesticides in the environment, capable of undergoing long range transport to remote locations such as the Arctic. It is practically water-insoluble, but readily adheres to clay particles and persists in soil and water for several years. Its indiscriminate and injudicious use in the control of insects on a wide range of agricultural products and in the extermination of house-hold pests, has considerably increased the hazard risk for human health. Also, this compound has a high fatality rate in humans when ingested accidentally, from food or water contaminated, or in suicidal cases. The aim of this article is to review and summarize chemical, biochemical, environmental, and toxicological data of endosulfan and draw attention to its toxicological potential risk to human health.

Alzheimer's disease (AD) is a progressive degenerative brain disease which causes mental and physical decline, gradually resulting in death. Currently, this disease represents one of the uppermost human issues, both from the medical and economic point of view. Interest in the discovery of a drug for AD is enormous. However, despite the long-term and worldwide effort for a more effective therapy, the only available treatment is a symptomatic use of acetylcholinesterase inhibitors (AChEIs) and memantine. New therapeutic approaches as well as those based on cholinergic or amyloid theory have not brought the desired benefits yet. Thus, the question is whether an effective drug for this progressive disease will ever be developed or whether people will have to rely only on prevention and minimize risk factors of AD.

No presente trabalho foi aplicada uma metodologia teórica desenvolvida em um trabalho anterior que utiliza os programas Molegro® e Spartan® para avaliar as constantes cinéticas de associação e reativação de oximas, em relação a resultados in vitro previamente reportados na literatura. Como observado antes, os resultados mostraram boa correlação entre as energias livres teóricas de ligação das oximas e os dados experimentais, corroborando a metodologia como adequada para a predição de parâmetros cinéticos e termodinâmicos, os quais podem ser úteis para o planejamento e seleção de novas e mais efetivas oximas.

In this work we applied a theoretical methodology developed in a former work, using the Molegro® and Spartan® softwares, to evaluate the association and kinetic reactivation constants of oximes, facing in vitro data previously reported in the literature. As reported before, results showed a good agreement between the theoretical binding free energies of the oximes and experimental data, corroborating the methodology as suitable for the prediction of kinetic and thermodynamic parameters that might be helpful for the design and selection of new and more effective oximes.

As doenças causadas por protozoários afetam hoje em dia uma grande parcela da população mundial, provocando muitas mortes e exercendo grande influência na qualidade de vida e no desenvolvimento de muitos países. Essas doenças afetam principalmente países pobres e por isso, a pesquisa e o desenvolvimento de novos fármacos são negligenciados. De fato, a maioria das drogas usadas no tratamento dessas doenças data de décadas passadas e apresentam muitas limitações, incluindo o aparecimento da resistência às drogas. Este artigo tem como foco os mais recentes desenvolvimentos publicados no campo de patentes, entre 2001-2008, com especial atenção a promissores compostos atuando contra tripanossomíase, leishmaniose, malária, toxoplasmose, amebíase, giardíase, balantidíase e pneumocistose.

Protozoan infections are parasitic diseases that affect hundreds of millions of people worldwide, but have been largely neglected for drug development because they affect poor people in poor regions of the world. Most of the current drugs used to treat these diseases are decades old and have many limitations, including the emergence of drug resistance. This review will focus on the most recent developments, from 2001 to 2008, published in the field of patents and publications, paying particular attention to promising compounds acting against trypanosomiasis, leishmaniasis, malaria, toxoplasmosis, amebiasis, giardiasis, balantidiasis and pneumocystosis, their chemistry and biological evaluation, and to new chemical and pharmaceutical processes.

A Serina Hidroximetiltransferase de Plasmodium falciparum nunca foi vista como alvo para a quimioterapia antimalarial, possivelmente devido a sua grande similaridade seqüencial com a enzima humana. Esta similaridade sugere que este parasita pode ser incapaz de mutar esta enzima para desenvolver resistência à quimioterapia. Neste trabalho, diferenças observadas no comportamento dinâmico dos sítios ativos da estrutura cristalográfica da enzima humana e um modelo, por homologia, da enzima do parasita, ambos complexados com glicina, como N-glicina-[3-hidróxi-2-metil-5-fosfonooximetil-piridin-4-il-metano], e ácido 5-formil-6-hidrofólico, foram utilizadas para o planejamento de inibidores seletivos desta enzima como novos potenciais antimalariais. Estes potenciais inibidores são derivados do ácido 5-formil-6-hidrofólico com diferentes cargas e comprimentos de cauda. Simulações por dinâmica molecular e estimativas das energias de interação dos compostos nos sítios ativos de ambas as enzimas mostraram que os compostos com carga líquida negativa e caudas curtas ou caudas longas e anfóteras, seriam potencialmente mais seletivos em relação à enzima do parasita.

Plasmodium falciparum Serine Hydroxymethyltransferase has never been used as target for antimalarial chemotherapy, possibly because its great sequence similarity with the human enzyme. This similarity suggests implies that P. falciparum may not be able to mutate this enzyme to develop resistance for chemotherapy. In this work, we have used differences on the dynamic behavior of the active sites of the crystallographic structure of the human enzyme and a homology model of parasite's enzyme, both in complex with glycine, as N-glycine-[3-hydroxy-2-methyl-5-phosphonooxymethyl-pyridin-4-yl-methane] and 5-formyl-6-hydrofolic acid, to design prototypes for selective inhibitors of this enzyme as new potential antimalarials. Those potential inhibitors are 5-formyl-6-hydrofolic acid derivatives with different charges and tail lengths. Molecular dynamics simulations and interaction energy estimates of the compounds within the active sites of both enzymes showed that compounds with a negative net charge and either shorter tails or longer amphoteric tails, would be more selective towards pfSHMT.

O conceito FERMO foi empregado com sucesso ao princípio ácido-base de dureza e moleza de Pearson para quatro ligantes ambidentados. Usando um postulado intuitivo basedo em argumentos HOMO-LUMO para a dureza e moleza, as diferenças de energia FERMO-LUMO descrevem corretamente os sítios duros e moles para os sistemas estudados. Além disso, os orbitais de Kohn-Sham e Hartree-Fock levam às mesmas conclusões.

The FERMO concept was successfully applied to the Pearson's Hard and Soft acid-base principle for four ambidentate ligands. Using an intuitive statement based on the HOMO-LUMO approach to the hardness and softness, the FERMO-LUMO gaps correctly describe the soft and hard sites in the studied systems. Moreover, Kohn-Sham and Hartree-Fock MOs lead to same conclusions.