Different origins of green-light photoluminescence emission in structurally ordered and disordered powders of calcium molybdate.

A strong greenish-light photoluminescence (PL) emission was measured at room temperature for disordered and ordered powders of CaMoO4 prepared by the polymeric precursor method. The structural evolution from disordered to ordered powders was accompanied by XRD, Raman spectroscopy, and TEM imagery. High-level quantum mechanical calculations in the density functional framework were used to interpret the formation of the structural defects of disorder powders in terms of band diagram and density of states. Complex cluster vacancies [MoO3 x V(O(z))] and [CaO7 x V(O(z))] (where V(O(z)) = V(O(X)), V(O(*)), V(O(**))) were suggested to be responsible to the appearance of new states shallow and deeply inserted in the band gap. These defects give rise to the PL in disordered powders. The natural PL emission of ordered CaMoO4 was attributed to an intrinsic slight distortion of the [MoO4] tetrahedral in the short range.

Pharmacokinetic and pharmacodynamic predictions of novel potential HIV-1 integrase inhibitors.

Virtual screening docking-based approach has been employed in order to select novel HIV-1 integrase (IN) potential inhibitors in large databases. Toxicity, metabolism and drug-like properties have been analyzed for the most promising compounds, using computational chemistry techniques. Results were compared and discussed with that obtained for a known HIV-1 (IN) inhibitor reported in the literature.

Virtual screening, molecular interaction field, molecular dynamics, docking, density functional, and ADMET properties of novel AChE inhibitors in Alzheimer's disease.

Alzheimer's disease (AD) affects approximately 10% of the world's population with 65 years of age, being the most common form of dementia in adults and is characterized by senile plaquets and cholinergic deficits. Many drugs currently used for the treatment of the AD are based on the improvement of cholinergic neurotransmission achieved by Acetylcholinesterase (AChE) inhibition, the enzyme responsible for acetylcholine hydrolysis. We have focused in this work on the usage of computer-aided molecular design by virtual screening, molecular dynamics with implicit and explicit water solvation, density functional, molecular interaction field studies, docking procedures, ADMET predictions in order to propose novel potential AChE inhibitor for the treatment of Alzheimer's disease.

ADMET properties, database screening, molecular dynamics, density functional, and docking studies of novel potential anti-cancer compounds.

Database screening was performed in a large database (hundreds of thousands of molecules which we optimized at the AM1 level) yielding a set of potential bioactive ligands. One new ligand was selected among the top solutions and optimized at the B3LYP/6-31G* level, yielding also NBO (Natural Bond Order) charges. A flexible docking program was used to investigate the interactions between the receptor and the new ligand. The stability as well as the main protein-ligand contacts of our proposed novel ligand as well as the crystallographic RAR ligand was investigated by molecular dynamics. The ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) properties as well as the parameters of the Rule of Five were investigated. The result of this work is compared with a crystallographic ligand of RAR. Our novel proposed anti-cancer ligand indicates hydrophobic interactions and strong polar interactions with the receptor.

Homology modeling and molecular interaction field studies of alpha-glucosidases as a guide to structure-based design of novel proposed anti-HIV inhibitors.

For AIDS therapy, there are currently a number of compounds available for multiple targets already approved by the FDA and in clinic, e.g. protease inhibitors, reverse transcriptase inhibitors (NRTI, NNRTI), fusion inhibitors, CCR4, CCR5 among others. Some pharmaceuticals act against the virus before the entrance of HIV into the host cells. One of these targets is the glucosidase protein. This novel fusion target has been recently explored because the synthesis of viral glycoproteins depends on the activity of enzymes, such as glucosidase and transferase, for the elaboration of the polysaccharides. In this work we have built an homology model of Saccharomyces cerevisiae glucosidase and superimposed all relevant glucosidase-like enzymes in complex with carbohydrates, and calculated as well molecular interaction fields in our S. cerevisiae active site model. Our results suggest that there are two saccharide binding sites which are the most important for the binding of inhibitors with this family of enzymes which supports the possibility of inhibitors containing only two sugar units. Based on these results, we have proposed a novel pseudo-dissacharide which is a potential pharmaceutical for AIDS treatment.

Molecular dynamics, database screening, density functional and docking studies of novel RAR ligands in cancer chemotherapy.

Due to the major challenge which cancer treatment and cure still imposes after many decades to the international scientific community, there is actually considerable interest in new ligands with increased bioactivity. We have focused on the retinoid acid receptor, which is considered an interesting target for drug design. In this work, we have carried out density functional geometry optimizations and different docking procedures. We have performed screening in a large database (hundreds of thousands of molecules which we optimized at the AM1 level) yielding a set of potential bioactive ligands. Two new ligands were selected and optimized at B3LYP/6-31G* level. A flexible docking program was used to investigate the interactions between the receptor and the new ligands. Molecular dynamics were performed in order to investigate the stability of the two ligands as well as the crystallographic RAR ligand inside the RAR active site. We also investigated the stability of all the main protein-ligand contacts. The parameters of the Rule of Five were investigated. The result of this work is compared with a crystallographic ligand of RAR. One of our theoretically bioactive new ligands indicates stronger and more polar and hydrophobic interactions with the receptor.

Computer-aided molecular design of novel glucosidase inhibitors for AIDS treatment.

Since the onset of the AIDS epidemic, some 20 million people have died and the estimate is that today close to 40 million are living with type 1 human immunodeficiency virus (HIV)/AIDS. About 14 thousands people are infected worldwide daily with this disease. Still, only a few pharmaceuticals are available for AIDS chemotheraphy. Some pharmaceuticals act against the virus before the entrance of the HIV into the host cells. One of these targets is the glucosidase protein. This class of enzymes has been recently explored because the synthesis of viral glycoproteins depends on the activity of enzymes, such as glucosidase and transferase, for the elaboration of the polysaccharides. In this work we study several glucosidase inhibitors. The DFT method is used to compute atomic charges and the ligand/receptor interaction was simulated with docking software. Analysis of the interactions of the proposed pharmaceutical, a pseudodisaccharide, with the Thermotoga maritima 4-alpha-glucanotransferase in complex with modified acarbose, the scores from docking as well as the graphical superposition of all the ligands, suggest that our molecular designed pseudo-disaccharide may be a potent glucosidase inhibitor.