| Letters
in Drug Design & Discovery
ISSN: 1570-1808
Letters in Drug Design &
Discovery
Volume 7, Number 10, December 2010
Contents
Graphical
Abstracts i-v
3´,4´-Dihydrospiro[piperidine-4,2´-(1´H)quinoline]
Derivatives as New Antioxidant Agents with Acetylcholinesterase
Inhibitory Property Pp. 710-715
V.V. Kouznetsov, L.Y.V. Méndez and A.M.
Acevedo
[Abstract] [Purchase
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Schiff Bases of Isatin: Inhibitory Potential
Towards Acetylcholinesterase and Butyrylcholinesterase
Pp. 716-720
K.M. Khan, U.R. Mughal, N. Ambreen, N.H. Rama, F. Naz,
S. Perveen and M.I. Choudhary
[Abstract] [Purchase
Article]
Synthesis and Cytotoxic Activity of 4-Aryl-4H-chromeno[4,3-d]
[1,2,3] selenadiazoles Pp. 721-725
H. Yin, Y. Huang and G. Song
[Abstract]
[Purchase
Article]
Anticancer Activity of Ocimum basilicum
and the Effect of Ursolic Acid on the Cytoskeleton of MCF-7
Human Breast Cancer Cells Pp. 726-736
K.A. Qamar, A. Dar, B.S. Siddiqui, N. Kabir,
H. Aslam, S. Ahmed, S. Erum, S. Habib and S. Begum
[Abstract] [Purchase
Article]
Synthesis and In Vitro Antimicrobial
Evaluation of 4-alkyl/aryl-1-(3-phenoxypropionyl)-thiosemicarbazides
Pp. 737-742
M. Wujec, Ag. Siwek, E. Kusmierz and J. Stefanska
[Abstract] [Purchase
Article]
Editor’s Choice
Synthesis and Antiproliferative Evaluation of Spirothiadiazolopyridazine
Derivatives Pp. 743-746
H. Sekkak, S. Mojahidi, E.M. Rakib, S. Abouricha,
A. Kerbal, C. Aiello and M. Viale
[Abstract] [Purchase
Article]
Design, Synthesis and Biological Evaluation
of Lipophilic Analogs of Anethol Trithione Pp. 747-753
X.-C. Li, W. Fan, L. Hai, S. Qian, Q.-Q. Xiao and
M. Guan
[Abstract] [Purchase
Article]
Evaluation of Substituted Benzaldehydes Against
Mycobacterium tuberculosis Pp. 754-758
M. de L. Ferreira, A.L.P. Candéa, M. das G.M. de
O. Henriques, M.C.S. Lourenço, C.R. Kaiser and
M.V.N. de Souza
[Abstract] [Purchase
Article]
Reduction in Burst Release from Poly(D,L-Lactide-Co-Glycolide)
Microparticles by Solvent Treatment Pp. 759-764
A.R. Ahmed, M. Ciper and R. Bodmeier
[Abstract] [Purchase
Article]
Mini-Review
Articles
“Renaissance” of the Yeast Two-Hybrid
System - Enhanced for Automation and High-Throughput to Support
Proteome-Wide Research Pp. 765-789
R. Rid, H. Hintner, J.W. Bauer and K.
Önder
[Abstract] [Purchase
Article]
Abstracts
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3´,4´-Dihydrospiro[piperidine-4,2´-(1´H)quinoline]
Derivatives as New Antioxidant Agents with Acetylcholinesterase
Inhibitory Property
V.V. Kouznetsov, L.Y.V. Méndez and A.M.
Acevedo
In vitro radical-cation scavenging capacity
and anti-AChE activities of 19 piperidine derivatives, including
dihydrospiro[piperidine-4,2´(1´H)quinolines]
7-19 and their precursor 4-allyl-4-arylaminopiperidines
1-6 were reported. Their data of bioassays
and calculated logP and TPSA parameters showed promising drug-like
properties. The best radical scavenging compound (TEAC 1.73
± 0.01), 6-methyl-3´,4´- dihydrospiro[piperidine-4,2´(1´H)quinoline]
8 showed IC50
value of 62.5 µM (20.0 µg/mL) using AChE assay.
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Article]
Schiff Bases of Isatin: Inhibitory Potential
Towards Acetylcholinesterase and Butyrylcholinesterase
K.M. Khan, U.R. Mughal, N. Ambreen, N.H. Rama, F. Naz,
S. Perveen and M.I. Choudhary
A series of different Schiff bases of isatin 1-20
was synthesized by the condensation of isatin with primary
aromatic amines. It was observed that some of these compounds
have the potential to inhibit acetylcholinesterase, whereas
some others showed specific activity against butyrylcholinesterase,
depending upon substitution on the aromatic ring. Compounds
9 and 20 showed weak acetylcholinesterase
inhibitory activity having IC50
values 28.3 ± 0.26 and 159 ± 2.9 µM, respectively.
Nonetheless, compounds showed a varying degree of activity
against butyrylcholinesterase with IC50 values in the range
of 2.8 ± 0.07-82.9 ± 2.2 µM. Compounds
5, 2, and 11
showed IC50 values 2.8 ±
0.07, 5.2 ± 0.10, and 8.1 ± 0.30 µM, respectively,
Their activity was compared with standard inhibitor galanthamine
IC50 = 0.5 ± 0.01
µM for acetylcholinesterase and IC50
= 8.5 ± 0.01 µM for butyrylcholinesterase, respectively.
The structures of all the synthesized compounds were confirmed
by spectroscopic analysis.
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Synthesis and Cytotoxic Activity of 4-Aryl-4H-chromeno[4,3-d]
[1,2,3] selenadiazoles Pp. 721-725
H. Yin, Y. Huang and G. Song
Fourteen 4-Aryl-4H-chromeno[4,3-d][1,2,3]
selenadiazole derivatives were synthesized by the reaction
of flavonone-4-semicarbazones with SeO2.
The structures of the target compounds 1a-n
were elucidated by 1H NMR,
IR spectra, ESI-MS and elemental analyses. The preliminary
cytotoxic activities of 1a-n against K562,
KB, A549, SMC-7721 and SGC-7901 cell lines were evaluated
by MTT method, indicating that most compounds displayed moderate
to good antiproliferative activities against K562 and KB cell
lines. Compounds 1m and 1n,
the most potent ones, were promising template for development
of novel potent antitumor agents.
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Article]
Anticancer Activity of Ocimum basilicum
and the Effect of Ursolic Acid on the Cytoskeleton of MCF-7
Human Breast Cancer Cells
K.A. Qamar, A. Dar, B.S. Siddiqui, N. Kabir,
H. Aslam, S. Ahmed, S. Erum, S. Habib and S. Begum
The anticancer activity of Ocimum basilicum
extract and its fractions was evaluated using human cancer
cell lines; active compound(s) residing in it were identified
and mechanism of their anti-proliferative action was explored.
Methanolic extract was fractionated into petroleum ether soluble
(PE-S) and insoluble (PE-I) fractions. These were evaluated
on HT-144, MCF-7, NCI-H460 and SF-268 cell lines using Sulforhodamine
B assay. Immunofluorescence microscopy was employed to study
their effects on the cytoskeleton and nuclei of MCF-7 cells.
Fractionation of PE-I (GI50:
5 µg/ml; LC50: 71 µg/ml
against MCF-7) led to the isolation of four compounds, mainly
ursolic acid (LC50: 18.6
µg/ml). Ursolic acid (100 µM) induced a significant
decrease in the percentage of cells in anaphase/telophase
stages along with F-actin aggregation and mitotic spindle
distortion. These results support anti-proliferative activity
of O. basilicum extract against MCF-7 cells which
may partly be due to effects of ursolic acid on F-actin and
microtubules.
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Article]
Synthesis and In Vitro Antimicrobial
Evaluation of 4-alkyl/aryl-1-(3-phenoxypropionyl)-thiosemicarbazides
M. Wujec, Ag. Siwek, E. Kusmierz and J. Stefanska
Eight new 4-alkyl/aryl-1-(3-phenoxypropionyl)-thiosemicarbazides
were synthesized by condensation of 3-phenoxypropionic acid
hydrazide with related isothiocyanates. All compounds were
tested in vitro for their antibacterial and antifungal
activity. One compound, 4-(4-chlorophenyl)-1-(3-phenoxypropionyl)-thiosemicarbazide,
showed high level of activity against Gram-positive species,
MICs range 12.5-50 μg/mL.
Semiempirical calculations of geometries, energies, and QSAR
parameters have been determined in hope to get insight into
different biological activity of closely related isomers.
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Article]
Synthesis and Antiproliferative Evaluation of
Spirothiadiazolopyridazine Derivatives
H. Sekkak, S. Mojahidi, E.M. Rakib, S. Abouricha,
A. Kerbal, C. Aiello and M. Viale
The 1,3-dipolar cycloaddition of N-aryl-C-ethoxycarbonylnitrile
imines to pyridazin-3-thione afforded novel spirothiadiazolopyridazines
in moderate to good yields. The reaction occurs regioselectively
at the exocyclic C=S bond. Some of the newly synthesized compounds
were tested for their in vitro antitumor activity
against three human and murine cell lines [human: A2780, (ovary,
carcinoma), A549 (lung, carcinoma); murine: P388 (leukaemia)].
Among the series, some compounds exhibited significant growth
inhibitory effects against cell lines P388.
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Article]
Design, Synthesis and Biological Evaluation
of Lipophilic Analogs of Anethol Trithione
X.-C. Li, W. Fan, L. Hai, S. Qian, Q.-Q. Xiao and
M. Guan
16 ADT carboxylate esters were prepared and
tested for their chemical characteristics, stability, bioavailability,
potency and toxicity. Considering the good bioavailability,
3a was selected for the pharmacology test,
and the result showed that the potency of 3a
was remarkably higher than that of ATT. Additionally, 3a
was also chosen for the acute toxicity test. The result indicated
that the prodrug 3a was more safer than ATT.
The study suggested the feasibility to improve the bioavailability
of ATT by using prodrug strategy.
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Article]
Evaluation of Substituted Benzaldehydes Against
Mycobacterium tuberculosis
M. de L. Ferreira, A.L.P. Candéa, M. das G.M. de
O. Henriques, M.C.S. Lourenço, C.R. Kaiser and
M.V.N. de Souza
A series of 48 commercial benzaldehydes have been evaluated
for their in vitro antibacterial activity against Mycobacterium
tuberculosis H37Rv,
using the Alamar Blue susceptibility test and the activity
expressed as the minimum inhibitory concentration (MIC) in
µg/mL. Benzaldehydes 39 and 41
exhibited a significant activity at 3.12 µg/mL. Although
commercial benzaldehydes have been largely used by many research
groups in search of news TB-drugs, they had not been tested
previously against Mycobacterium tuberculosis. This
study adds important information to the rational design of
new lead anti-TB drugs.
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Article]
Reduction in Burst Release from Poly(D,L-Lactide-Co-Glycolide)
Microparticles by Solvent Treatment Pp. 759-764
A.R. Ahmed, M. Ciper and R. Bodmeier
A high initial burst release of an antisense
oligonucleotides drug from poly(lactide-co-glycolide) (PLGA)
microparticles prepared by the multiple emulsion (w/o/w) method
was significantly reduced, when the microparticles were treated
with a polymer non-solvent (ethanol)/water mixture. The ethanol/water
mixture acted like a plasticizer and significantly decreased
the glass transition temperature (Tg) of the PLGA.
Thus, PLGA microparticles in the wet state became soft, and
the surface pores were fused together during treatment. As
a result, microparticles with reduced surface pores that released
a low initial burst were obtained. The reduction in the initial
burst was more significant for the smaller microparticles
(<50 µm) and decreased with increasing microparticle
size. A less significant reduction in the initial burst was
observed when the microparticles were treated with a polymer
solvent (e.g., acetone)/water mixture.
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“Renaissance” of the Yeast Two-Hybrid
System - Enhanced for Automation and High-Throughput to Support
Proteome-Wide Research
R. Rid, H. Hintner, J.W. Bauer and K.
Önder
The recently introduced concept of “interactomics”
or “associomics” - defined as the complete repertoire
of physical protein-protein interactions (PPIs), ranging from
temporary (co-expression of interacting proteins), spatial
(cell compartment or specific cell-type existence), conditional
(disease-health state) or transient functional pairings to
the formation of stable, permanent complexes - presents us
with a variety of technical research challenges. Its main
bottleneck, however, remains the restricted number of currently
available high-throughput screening (HTS) techniques capable
of PPI detection. One of the most popular and effective methods
is in this context the yeast two-hybrid (Y2H) system which
has (despite some undeniable practical limitations) been used
in thousands of experimental settings, accounting for the
majority of all published PPI data. Therefore, this mini-review
summarizes the basic principles and most valuable modifications
that have been developed since the introduction of the Y2H
system by Fields and Song 20 years ago, and describes its
recent expansion towards automation and high-throughput application
obligatory for the global investigation of the eukaryotic
proteome. Finally, we take a close look at a choice of currently
available large-scale analytical strategies (with special
emphasis on the human interactome) some of which have already
culminated in comprehensive, partly interconnected maps, but
which are, nevertheless, still too incomplete to assemble
a true picture of all physiologically significant PPIs within
the living cell. For this reason, the HTS upgraded Y2H system
- in combination with other approaches - will continue to
provide an essential tool for the detailed dissection and
further characterization of proteome-wide PPIs on a systems
biology scale.
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