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The Density Functional Theory (DFT) method and the 6-31G** basis set were employed to calculate the molecular properties of artemisinin and 20 derivatives with different degrees of cytotoxicity against the human hepatocellular carcinoma HepG2 line. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) were employed to select the most important descriptors related to anticancer activity. The significant molecular descriptors related to the compounds with anticancer activity were the ALOGPS_log, Mor29m, IC5 and GAP energy. The Pearson correlation between activity and most important descriptors were used for the regression partial least squares (PLS) and principal component regression (PCR) models built. The regression PLS and PCR were very close, with variation between PLS and PCR of R(2) = ± 0.0106, R(2)(ajust) = ± 0.0125, s = ± 0.0234, F(4,11) = ± 12.7802, Q(2) = ± 0.0088, SEV = ± 0.0132, PRESS = ± 0.4808 and SPRESS = ± 0.0057. These models were used to predict the anticancer activity of eight new artemisinin compounds (test set) with unknown activity, and for these new compounds were predicted pharmacokinetic properties: human intestinal absorption (HIA), cellular permeability (PCaCO2), cell permeability Maden Darby Canine Kidney (PMDCK), skin permeability (P(Skin)), plasma protein binding (PPB) and penetration of the blood-brain barrier (C(Brain/Blood)), and toxicological: mutagenicity and carcinogenicity. The test set showed for two new artemisinin compounds satisfactory results for anticancer activity and pharmacokinetic and toxicological properties. Consequently, further studies need be done to evaluate the different proposals as well as their actions, toxicity, and potential use for treatment of cancers.

This work was carried out in collaboration between all authors. Authors MTP, NSRS and JCTC designed the study, wrote the protocol, involved in writing the first draft, participated in experiments and data collection. Authors CCL, FSB, CFS and JSC managed the literature search, analyses of the study and manuscript preparation. Author CBRS, FSB and JSC performed the statistical analysis and also aided in data interpretation and was actively involved in reading the manuscript. All authors read and approved the final manuscript.

The central importance of quantum chemistry is to obtain solutions of the Schrodinger equation for the accurate determination of the properties of atomic and molecular systems that occurred from the calculation of wave functions accurate for many diatomic and polyatomic molecules, us- ing Self Consistent Field method (SCF). The application of quantum chemical methods in the study and planning of bioactive compounds has become a common practice nowadays. From the point of view of planning it is important to note, when it comes to the use of molecular modeling, a collec- tive term that refers to methods and theoretical modeling and computational techniques to mimic the behavior of molecules, not intend to reach a bioactive molecule simply through the use of computer programs. The choice of method for energy minimization depends on factors related to the size of the molecule, parameters of availability, stored data and computational resources. Mo- lecular models generated by the computer are the result of mathematical equations that estimate the positions and properties of the electrons and nuclei, the calculations exploit experimentally, the characteristics of a structure, providing a new perspective on the molecule. In this work we show that studies of Highest Occupied Molecular Orbital Energy (HOMO), Low Unoccupied Mole- cular Orbital Energy (LUMO) and Map of molecular electrostatic potential (MEP) using Hatree- Fock method with different basis sets (HF/3-21G*, HF/3-21G**, HF/6-31G, HF/6-31G*, HF/ * Corresponding author.

Malaria is a parasitic disease which has as etiological agents protozoa of the genus Plasmodium prevalent in tropical countries. The appearance of Plasmodium strains resistant to artemisinin has become necessary the development of new drugs using computational tools to combat this epidemic. Diverse transporter proteins can act as antimalarials targets, thereby being the enzyme deoxyhypusine synthase a promising antimalarial target. The present study aimed to investigate 15 most active inhibitors of deoxyhypusine synthase target, deposited in databases Binding DB, in order to trace a pattern of physicochemical, pharmacokinetic and toxicological properties of the inhibitors for this enzyme and propose new inhibitors of deoxyhypusine synthase target. The physicochemical properties were obtained according to the Lipinski parameters to evaluate oral absorption. Based on the certain properties were proposed three new inhibitors (A, B and C). The ADME/Tox properties were calculated for new inhibitors compared with results of the selected compounds. The fifteen inhibitors for oral administration showed satisfactory results, because they have adapted to the Lipinski parameters. In relation to the penetration of the blood-brain barrier the inhibitors analyzed showed penetration values less than 1, and ranged from 0.0411815 to 0.481764, being that the compound 1 showed value of CBrain/CBlood = 0.135467. Compound B showed a higher strength in plasma protein binding in relation to the compound 1, having a variation be-tween them of ±1.489344. Therefore, the compound B would present a longer halflife compared with compound 1. The proposed compounds showed positive and satisfactory results, being able to reach less adverse effects related to the central nervous system depending of administered dose.

Made available in DSpace on 2018-11-26T17:44:45Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-01-01 Statement of problem. Bond strength (BS) values from in vitro studies are useful when dentists are selecting an adhesive system, but there is no ideal measuring method. Purpose. The purpose of this in vitro study was to investigate the influence of the evaluation method in the BS between dentin and composite resin. Material and methods. Molars with exposed superficial dentin (N=240) were divided into 3 groups according to the test: microtensile (mu TBS), microshear (mu SBS), and micropush-out (mu PBS). Each one was subdivided into 4 groups according to the adhesive system: total etch, 3- and 2-step; and self-etch, 2- and 1-step). For the mu PBS test, a conical cavity was prepared and restored with composite resin. An occlusal slice (1.5 mm in thickness) was obtained from each tooth. For the SBS test, a composite resin cylinder (1 mm in diameter) was built on the dentin surface of each tooth. For the mu TBS test, a 2-increment composite resin cylinder was built on the dentin surface, and beams with a sectional area of 0.5 mm(2) were obtained. Each subgroup was divided into 2 (n=10) as the specimens were tested after 7 days and 1 year of water storage. The specimens were submitted to load, and the failure recorded in units of megapascals. Original BS values from the mu TBS and mu SBS tests were normalized for the area from mu PBS specimens. Original and normalized results were submitted to a 3-way ANOVA (alpha=.05). The correlation among mechanical results, stress distribution, and failure pattern was investigated. Results. Significant differences (P.05). Within the 7 days of storage, the original BS values from mu TBS were significantly higher (P

The peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor that acts as a transcription factor, regulating glucose, lipid and inflammation signaling and it is exploited in type 2 diabetes treatment. However, the selective activation of this PPAR subtype has been linked to important adverse effects which can be mitigated through concomitant activation of PPARα and PPARδ. In this study, we proposed new PPARγ agonists using PharmaGist Server for pharmacophore prediction, the molecular docking was performed by GOLD (genetic optimization for ligand docking) v2.2, AutoDock 4.2 and AutoDock Vina 1.1 and QikProp v4.0 and Derek for absorption, distribution, metabolism, excretion and toxicity (ADMET) assessment. One molecule showed high predicted affinity to PPARγ and favorable pharmacokinetic and toxicity properties. It was then evaluated against PPARα and PPARδ and showed greater affinity to these receptors than the controls. Therefore this molecule is a promising drug lead for the development of derivatives and for the treatment of metabolic syndrome with the benefits of a PPAR pan activation.