To better understand the biological properties of cupuassu seed residue resulting from fruit industrial processing, its antioxidant activity was determined by both the 2,2‐diphenyl‐1‐picrylhydrazyl and 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) assays. Molecular modeling was used to correlate the antiradical power of eleven known cupuassu phenolic compounds with their structures. The extract antioxidant activity by both methods was very high compared with those of similar residues. The properties of the highest occupied and lowest unoccupied molecular orbitals indicate that the most energetically stable compounds possess the highest antioxidant activity. This was confirmed through the molecular electrostatic potential map by the nucleophilic surfaces on the oxygen atoms of carbonyl and hydroxyl groups.
Plasmepsin (PM) II is one of four enzymes in the food vacuole of Plasmodium falciparum. It has become an attractive target for combating malaria through research regarding its importance in the P. falciparum metabolism and life cycle, making it the target of choice for structure-based drug design. This paper reports the results of hybrid quantum mechanics / molecular mechanics (QM/MM) molecular dynamics (MD) simulations employed to study the details of the interactions established between PM II and N-(3-{(2-benzo[1, 3]dioxol-5-yl-ethyl)[3-(1-methyl-3-oxo-1,3-dihydro-isoindol-2-yl) propionyl]-amino}-1-benzyl-2-(hydroxyl-propyl)-4-benzyloxy-3,5dimethoxy-benzamide (EH58), a well-known potent inhibitor for this enzyme. Electrostatic binding free energy and energy terms decomposition have been computed for PM II complexed with the EH58 inhibitor. The results reveal that there is a strong interaction between Asp34, Val78, Ser79, Tyr192 and Asp214 residues and the EH58 inhibitor. In addition, we have computed the potential of the mean force (PMF) profile in order to assign the protonation state of the two catalytic aspartates in PM II-EH58 complex. The results indicate that the protonation of Asp214 favors a stable active site structure, which is consistent with our electrostatic binding free energy calculation and with previous published works.
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Drug delivery systems are constantly evolving and developing, as well as the search for promising and effective formulations for drug delivery. Computational simulation methods enable the development of complex systems, such as nanostructured lipid carriers (NLC), the understanding of interaction and dynamics between drug molecule and its transporter. In this work, aimed to simulate a NLC containing cupuassu fat triacylglycerols, carnauba wax and caprylic/capric acid triacylglycerol, stabilized with Tween 80 and Pluronic and ketoconazole enantiomer as drug was simulated. Initially, lipid mixtures were studied by Differential Scanning Calorimetry and X-ray diffraction. Subsequently, computational studies were carried out, among which Molecular Docking of ketoconazole to the lipid mixture and Molecular Dynamics of NLC system containing ketoconazole. From the results obtained it was possible to observe the main binding affinities of the drug and provide a better NLC formulation. It was also possible to propose a three-dimensional NLC model that was stable after molecular dynamics and ideal for future experimental studies.
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