19 research outputs found
A Quantitative Structure-Activity Relationships (QSAR) Study of Piperine Based Derivatives with Leishmanicidal Activity
Leishmaniasis is a parasitic disease which represents a serious public health problem in developing countries. It is considered a neglected tropical disease, for which there is little initiative in the search for therapeutic alternatives by pharmaceutical industry. Natural products remain a great source of inspiration for obtaining bioactive molecules. In 2010, Singh and co-workers published the synthesis and in vitro biological activity of piperoyl-aminoacid conjugates, as well as of piperine, against cellular cultures of Leishmania donovani. The piperine is an alkaloid isolated from Piper nigrum that has many activities described in the literature. In this work, we present a Quantitative Structure-Activity Study of piperine derivatives tested by Singh and co-workers, aiming to highlight important molecular features for leishmanicidal activity, obtaining a mathematical model to predict the activity of new analogs. Compounds were submitted to a geometry optimization computational procedure at semiempirical level of quantum theory. Molecular descriptors for the set of compounds were calculated by E-Dragon online plataform, followed by a variable selection procedure using Ordered Predictors Selection algorithm. Validation parameters obtained showed that a good QSAR model, based on multiple linear regression, was obtained (R2 = 0.85; Q2 = 0.69), and the following conclusions regarding the structure-activity relationship were elucidated: Compounds with electronegative atoms on different substituent groups of analogs, absence of unsaturation on lateral chain, presence of ester instead of carboxyl, and large volumes (due the presence of additional aromatic rings) trends to increase the activity against promastigote forms of leishmania.
DOI: http://dx.doi.org/10.17807/orbital.v9i1.89
Reverse and Forward Engineering of Local Voltage Control in Distribution Networks
The increasing penetration of renewable and distributed energy resources in
distribution networks calls for real-time and distributed voltage control. In
this paper we investigate local Volt/VAR control with a general class of
control functions, and show that the power system dynamics with non-incremental
local voltage control can be seen as distributed algorithm for solving a
well-defined optimization problem (reverse engineering). The reverse
engineering further reveals a fundamental limitation of the non-incremental
voltage control: the convergence condition is restrictive and prevents better
voltage regulation at equilibrium. This motivates us to design two incremental
local voltage control schemes based on the subgradient and pseudo-gradient
algorithms respectively for solving the same optimization problem (forward
engineering). The new control schemes decouple the dynamical property from the
equilibrium property, and have much less restrictive convergence conditions.
This work presents another step towards developing a new foundation -- network
dynamics as optimization algorithms -- for distributed realtime control and
optimization of future power networks
Quantitative Structure-Activity Relationship (QSAR) Studies of Morita-Baylis- Hillman Adducts bioactive against Leishmania amazonensis.
The Morita-Baylis-Hillman Adducts (MBHA) is a class of molecules studied
by our research group on synthetic, theoretical and bioactivity aspects. In this work,
we present Quantitative Structure-Activity Relationship (QSAR) models involving 32
aromatic MBHA. Initially, the most stable conformations of thirty-two MBHA were
investigated by theoretical methods, which were used to construct models. For this
study, were obtained potential energy curves using AM1 semi-empirical method,
considering rotational degrees of freedom (sigma bonds). From these curves, the
less energy conformation to each molecule was selected and optimized at B3LYP/6-
31+G(d) level, considering solvent effects through Polarizable Continuum Model
(PCM). Proton Nuclear Magnetic Ressonance data are in agreement with the
conformational study. Intramolecular Hydrogen Bonds (IHB) are presents in the most
of the studied compounds, according to structural characterization and QTAIM
calculations. Curiously, compounds that showed hydrogen bonds involving the nitro
and hydroxyl groups have the best values of biological activity (IC50). An explanation
is based on redox mechanism of action of nitrocompounds. NBO (Natural Bond
Orbital) charges and LUKO (Lowest Unoccupied Kohn-Sham Orbitals) analysis at the
ortho-nitro group are in agreement with these analyses. Considering quantum
calculations and structural observations, four descriptors were selected a priori and
submitted to a QSAR study using PLS (Partial Least Squares) and MLR (Multiple
Linear Regression) modeling. A second QSAR approach was made from the another
set of descriptors obtained through the online platform E-DRAGON, which were
submitted to a variable selection method. The quality parameters obtained for models
indicate that both are robust and predictive.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESOs Adutos de Morita-Baylis-Hillman (AMBH) compreendem uma classe de
moléculas investigadas por nosso grupo de pesquisas nos aspectos sintéticos,
teóricos e de bioatividade. Neste trabalho, apresentamos modelos de Relação
Quantitativa entre a Estrutura Química e a Atividade Leishmanicida (QSAR)
envolvendo 32 AMBH aromáticos. Deste modo, inicialmente foram investigadas as
conformações mais estáveis de cada composto através de métodos teóricos, as
quais foram utilizadas na construção dos modelos. Foram obtidas curvas de energia
potencial utilizando o método semi-empírico AM1, considerando graus de liberdade
rotacionais (ligações sigma). A partir destas curvas, a conformação de menor
energia para cada molécula foi selecionada e otimizada ao nível B3LYP/6-31+G(d),
considerando os efeitos do solvente aquoso usando PCM ( Polarizable Continuum
Model ). Dados espectroscópicos de Ressonância Magnética Nuclear de prótons
corroboraram o estudo conformacional. Ligações de Hidrogênio Intramoleculares
(LHI) se mostraram presentes na maioria das moléculas estudadas, conforme
caracterização estrutural e cálculos QTAIM ( Quantum Theory Atoms in Molecules ).
Curiosamente, os compostos que apresentaram Ligações de Hidrogênio envolvendo
o grupo nitro (NO2) e a hidroxila (OH) possuem melhores valores de atividade
biológica (menor IC50). Uma explicação está baseada no mecanismo de ação redox
de nitrocompostos. Observação das cargas NBO ( Natural Bond Orbitals ) e análise
dos orbitais de fronteira LUKO ( Lowest Unoccupied Kohn-Sham Orbitals ) ao nível
do grupo orto-nitro estão de acordo com estas análises. Considerando os cálculos
quânticos, bem como observações estruturais, quatro descritores foram
selecionados a priori e submetidos a um estudo QSAR ( Quantitative Structure-
Activity Relationships ) utilizando modelagem PLS ( Partial Least Squares ) e MLR
( Multiple Linear Regression ). Uma segunda abordagem QSAR foi realizada a partir
de outro conjunto de descritores obtidos através da plataforma online E-DRAGON,
os quais foram submetidos ao método de seleção de variáveis OPS ( Ordered
Predictor Selection ). Os parâmetros de qualidade obtidos para os modelos indicam
que ambos são robustos e preditivos
Complexation with β-cyclodextrin enhances apoptosis-mediated cytotoxic effect of harman in chemoresistant BRAF-mutated melanoma cells
International audienc
Bis-nor-diterpene from Cnidoscolus quercifolius (Euphorbiaceae) induces tubulin depolymerization-mediated apoptosis in BRAF-mutated melanoma cells
International audienc
Effect of LASSBio-1586 (10, 20 and 40 mg/kg, p.o.) and indomethacin (20 mg/kg, p.o.) on cotton pellet-induced granuloma.
<p>Values are expressed as the mean ± S.E.M. (n = 6, per group), where <i>a</i> indicates <i>p</i><0.05, significantly different from the control group, according to ANOVA, followed by Tukey’s test.</p
Results of the docking procedures for LASSBio-1586.
<p><b>(A)</b> Conformations obtained from the most populous and stable cluster in the binding site of COX-2; <b>(B)</b> most stable docked conformation for LASSBio-1586 (Binding Energy = −7.84 Kcal/mol); <b>(C)</b> native conformation of meloxicam (magenta) and most stable conformation for LASSBio-1586 (cyan).</p