Albérico B. F. da Silva

Infrared Spectroscopy of Anionic, Cationic, and Zwitterionic Surfactants

This paper describes the ordering degree of anionic, cationic, and zwitterionic surfactants with the increase of their packing density on Ge substrate by using Fourier transform infrared-attenuated total reflection (FTIR-ATR) spectroscopy. This work shows new insights on the conformational order of sodium dodecyl sulfate (SDS), N-hexadecyl-N-N-dimethyl-3-ammonio-1-propane-sulfonate (HPS), hexadecyl-trimethylammonium bromide (CTAB), and dodecyl trimethylammonium bromide (DTAB). DFT and semiempirical calculations are also performed in order to evaluate the effect of headgroup hydration and counterion. The CH2 asymmetric and symmetric stretching bands for the SDS molecule show a shift of 1.7 and 0.9 cm−1 to higher frequencies as the packing density increases, while it is observed a shift of 2.6 and 2.7 cm−1 for the HPS molecule, respectively. The DTAB molecule shows a shift of 4.5 cm−1 to lower frequencies for both CH2 asymmetric and symmetric stretching bands as the packing density increases, indicating the decrease of gauche conformations and the increase of all-trans conformations over the aliphatic chain.

Novel insights for dihydroorotate dehydrogenase class 1A inhibitors discovery.

The enzyme dihydroorotate dehydrogenase (DHODH) has been suggested as a promising target for the design of trypanocidal agents. We report here the discovery of novel inhibitors of Trypanosoma cruzi DHODH identified by a combination of virtual screening and ITC methods. Monitoring of the enzymatic reaction in the presence of selected ligands together with structural information obtained from X-ray crystallography analysis have allowed the identification and validation of a novel site of interaction (S2 site). This has provided important structural insights for the rational design of T. cruzi and Leishmania major DHODH inhibitors. The most potent compound (1) in the investigated series inhibits TcDHODH enzyme with Kiapp value of 19.28 μM and possesses a ligand efficiency of 0.54 kcal mol(-1) per non-H atom. The compounds described in this work are promising hits for further development.

Non-peptidic Cruzain Inhibitors with Trypanocidal Activity Discovered by Virtual Screening and In Vitro Assay

A multi-step cascade strategy using integrated ligand- and target-based virtual screening methods was developed to select a small number of compounds from the ZINC database to be evaluated for trypanocidal activity. Winnowing the database to 23 selected compounds, 12 non-covalent binding cruzain inhibitors with affinity values (K i) in the low micromolar range (3–60 µM) acting through a competitive inhibition mechanism were identified. This mechanism has been confirmed by determining the binding mode of the cruzain inhibitor Nequimed176 through X-ray crystallographic studies. Cruzain, a validated therapeutic target for new chemotherapy for Chagas disease, also shares high similarity with the mammalian homolog cathepsin L. Because increased activity of cathepsin L is related to invasive properties and has been linked to metastatic cancer cells, cruzain inhibitors from the same library were assayed against it. Affinity values were in a similar range (4–80 µM), yielding poor selectivity towards cruzain but raising the possibility of investigating such inhibitors for their effect on cell proliferation. In order to select the most promising enzyme inhibitors retaining trypanocidal activity for structure-activity relationship (SAR) studies, the most potent cruzain inhibitors were assayed against T. cruzi-infected cells. Two compounds were found to have trypanocidal activity. Using compound Nequimed42 as precursor, an SAR was established in which the 2-acetamidothiophene-3-carboxamide group was identified as essential for enzyme and parasite inhibition activities. The IC50 value for compound Nequimed42 acting against the trypomastigote form of the Tulahuen lacZ strain was found to be 10.6±0.1 µM, tenfold lower than that obtained for benznidazole, which was taken as positive control. In addition, by employing the strategy of molecular simplification, a smaller compound derived from Nequimed42 with a ligand efficiency (LE) of 0.33 kcal mol−1 atom−1 (compound Nequimed176) is highlighted as a novel non-peptidic, non-covalent cruzain inhibitor as a trypanocidal agent candidate for optimization.

The nuclear electric quadrupole moment of antimony from the molecular method

Relativistic Dirac-Coulomb (DC) Hartree-Fock calculations are employed to obtain the analytic electric field gradient (EFG) on the antimony nucleus in the SbN, SbP, SbF, and SbCl molecules. The electronic correlation contribution to the EFGs is included with the DC-CCSD(T) and DC-CCSD-T approaches, also in the four-component framework, using a finite-difference method. The total EFG results, along with the experimental nuclear quadrupole coupling constants from microwave spectroscopy, allow to derive the nuclear quadrupole moments of (121)Sb and (123)Sb, respectively, as -543(11) and -692(14) mb.

Aspectos terapêuticos de compostos da planta Cannabis sativa

Several cannabinoid compounds present therapeutic properties, but also have psychotropic effects, limiting their use as medicine. Nowadays, many important discoveries on the compounds extracted from the plant Cannabis sativa (cannabinoids) have contributed to understand the therapeutic properties of these compounds. The main discoveries in the last years on the cannabinoid compounds were: the cannabinoid receptors CB1 and CB2, the endogenous cannabinoids and the possible mechanisms of action involved in the interaction between cannabinoid compounds and the biological receptors. So, from the therapeutical aspects presented in this work, we intended to show the evolution of the Cannabis sativa research and the possible medicinal use of cannabinoid compounds.

Propriedades químico-quânticas empregadas em estudos das relações estrutura-atividade

In this work we show that structure-activity relationship studies are of great importance in modern chemistry and biochemistry. In order to obtain a significant correlation, it is crucial that appropriate descriptors be employed. Thus, quantum chemical calculations are an attractive source of new molecular descriptors which can, in principle, express all the electronic and geometric properties of molecules and their interactions with the biological receptor.

The basic antioxidant structure for flavonoid derivatives.

AbstractAn antioxidant structure–activity study is carried out in this work with ten flavonoid compounds using quantum chemistry calculations with the functional of density theory method. According to the geometry obtained by using the B3LYP/6-31G(d) method, the HOMO, ionization potential, stabilization energies, and spin density distribution showed that the flavonol is the more antioxidant nucleus. The spin density contribution is determinant for the stability of the free radical. The number of resonance structures is related to the π-type electron system. 3-hydroxyflavone is the basic antioxidant structure for the simplified flavonoids studied here. The electron abstraction is more favored in the molecules where ether group and 3-hydroxyl are present, nonetheless 2,3-double bond and carbonyl moiety are facultative. FigureThe basic antioxidant structure for flavonoid derivatives

A Structure-Activity Relationship (SAR) Study of Neolignan Compounds with Anti-schistosomiasis Activity

A set of eighteen neolignan derivative compounds with anti-schistosomiasis activity was studied by using the quantum mechanical semi-empirical method PM3 and other theoretical methods in order to calculate selected molecular properties (variables or descriptors) to be correlated to their biological activities. Exploratory data analysis (principal component analysis, PCA, and hierarchical cluster analysis, HCA), discriminant analysis (DA) and the Kth nearest neighbor (KNN) method were employed for obtaining possible relationships between the calculated descriptors and the biological activities studied and predicting the anti-schistosomiasis activity of new compounds from a test set. The molecular descriptors responsible for the separation between active and inactive compounds were: hydration energy (HE), molecular refractivity (MR) and charge on the C19 carbon atom (Q19). These descriptors give information on the kind of interaction that can occur between the compounds and their respective biological receptor. The prediction study was done with a new set of ten derivative compounds by using the PCA, HCA, DA and KNN methods and only five of them were predicted as active against schistosomiasis.

Estudo eletroquímico e químico-quântico da oxidação do antidepressivo tricíclico amitriptilina

This work presents the electrochemical and quantum chemical studies of the oxidation of the tricyclic antidepressant amitriptyline (AM) employing a carbon-polyurethane composite electrode (GPU) in a 0.1 mol L-1 BR buffer. The electrochemical results showed that the oxidation of AM occurs irreversibly at potentials close to 830 mV with the loss of one electron and one proton and is controlled by reagent and product adsorption. According to the PM3 results, the atom C16 is the region of highest probability for the oxidation of AM since it has the largest charge variation.

An accurate relativistic universal Gaussian basis set for hydrogen through Nobelium without variational prolapse and to be used with both uniform sphere and Gaussian nucleus models.

An accurate relativistic universal Gaussian basis set (RUGBS) from H through No without variational prolapse has been developed by employing the Generator Coordinate Dirac–Fock (GCDF) method. The behavior of our RUGBS was tested with two nuclear models: (1) the finite nucleus of uniform proton‐charge distribution, and (2) the finite nucleus with a Gaussian proton‐charge distribution. The largest error between our Dirac–Fock–Coulomb total energy values and those calculated numerically is 8.8 mHartree for the No atom.