| Letters
in Drug Design & Discovery
ISSN: 1570-1808
Letters in Drug Design &
Discovery
Volume 3, Number 8, October 2006
| Synergistic Effect of Immunotherapy
and Chemotherapy in Cancers: Perspective in High Grade
Glioma Treatment Pp. 513-523 |
G.R. DeAngulo, W. Sun &
A.B. Heimberger
Chemotherapy and immunotherapy are two distinct
approaches for the treatment for high-grade gliomas.
Used independently, neither is curative. However,
if the appropriate chemotherapeutic agent is selected
and its administration is timed in conjunction with
immunotherapy, a potent synergistic effect may occur,
resulting in a more favorable outcome. |
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| Analysis of Brostallicin Effect
on Different Human Gastrointestinal Cancer Cell Lines
Pp. 524-527 |
A.I. Scovassi, C. Gorrini, W.
Pastori & M. Ciomei
Brostallicin, a specific adenine-thymine minor groove
binder belonging to a new class of distamycin A-derivatives
proved to be active in vitro against a
panel of human tumor cell lines. We demonstrated
the cytotoxic and apoptotic potential of this compound
on gastric and colon cancer cell lines with either
wt or mutated p53. |
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| Cytotoxicity and Antiviral Activity
of Palladium(II) Quinolylmethylphosphonate Complexes.
Synthesis of Acetate Complexes Pp. 528-533 |
Palladium(II) acetate complexes of alkyl quinolylmethylphos-phonates
were synthesized and evaluated for their cytotoxic
and antiviral activity in vitro in different
cell lines. Structure-activity relationship studies
comprise acetate and chloro complexes. Good cell
growth inhibitory effects were observed for dichloro
adduct and acetate bridged dimer of diethyl 8 quinolylmethylphosphonate
(8-dqmp). |
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| Small Molecule De-Repression of
BAX and BAK Oligomerization as a Strategy for Treating
Cancer Pp. 534-540 |
N. Crawford & D.A. Fennell
The multidomain pro-apoptotic BCL-2 family
proteins BAX and BAK are critical effectors of apoptosis
(programmed cell death) a prerequisite for effective
cancer cell killing by drugs and radiotherapy. Cancer
cells commonly express BCL-2 family anti-apoptotic
inhibitors of BAX and BAK that may be antagonized
by a growing family of small molecules to be discussed
in this review in the context of novel therapy. |
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| Anti-EGFR Strategy for Colorectal
Cancer: Searching for the Real Target Pp. 541-543 |
A. Zaniboni & F. Meriggi
Anti-EGFR strategy has shown promising antitumor
activity in colorectal cancer. Positive EGFR status
by immunohistohemistry of a tumor specimen is presently
mandated to determine candidacy for this therapy,
although this assay appears to be suboptimal and
newer assessment techniques to determine suitability
for therapy must be developed. |
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| Synthesis and In Vitro
Biological Activity Evaluation of the Derivatives of Combretastatin
A-4 Pp. 544-546 |
Z. Yang
Combretastatin A-4, a natural compound isolated
from the bark of the South African bush willow tree
Combretum caffrum (Combretaceae), is one
of the most potent anti-tumor agents. The synthesis
and in vitro biological activity evaluation
of the analogs of Combretastatin-4 are reported. |
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| Syntheses of Disaccharide Units
of Manβ(1→6)Man,
Manα(1→6)Man
and Glcα(1→6)Man,
and Their Interactions for Concanavalin A Pp.
547-549 |
T. Yamanoi, H. Hamada, Y. Oda
& K. Hattori
We investigated to synthesize the disaccharide units
of Manβ(1→6)Manα→OPh,
Manα(1→6)Manα1→OPh
and Glcα(1→6)Manα1→OPh
as the analogues of the α(1→6)
arm of the mannotrisaccharide core in N-linked
glycopeptides by the dimethylphosphinothioate method.
Studies using a surface plasmon resonance optical
biosensor indicated that the Manβ(1→6)Manα1→OPh
had an association constant of 1.15 x 104
M-1 for immobilized Concanavalin A, whose
value almost corresponded to that of the Manα(1→6)Manα1→OPh. |
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| QSAR Study of Benzothiazole Derivatives
as p561ck Inhibitors Pp.
550 560 |
A.M. Badiger, M.N. Noolvi &
P.V. Nayak
QSAR study of benzothiazoles derivatives using Molecular
Operating Environment (MOE) is reported. The study
revealed various structural and physicochemical
properties required to achieve better enzyme-inhibitor
interaction. |
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| Discovery of a Non-β-Lactam
Inhibitor of Escherichia Coli L, D-Carboxypeptidase
A Using a Coupled Fluorescent Assay Pp. 561-566 |
E.Z. Baum
During peptidoglycan recycling in Escherichia
coli, L, D-carboxypeptidase A\ cleaves the
tetrapeptide L-Ala-γ-D-Glu-meso-diaminopimelic
acid-D-Ala, producing tripeptide and D-Ala. Previous
studies utilized substrate purified from bacteria,
with HPLC detection of tripeptide. Herein, synthetic
peptide substrate containing L-Lys in place of diaminopimelic
acid, and a fluorescent assay for D-Ala, were used
to identify a benzoxazine as a non-β-lactam
inhibitor of the enzyme. |
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| Microtubules and Commuting Receptors
Pp. 567-568 |
Microtubules interfering agents modulate function
of various commuting receptors in distinct ways. |
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| Can Binding Kinetics Translate
to a Clinically Differentiated Drug? From Theory to Practice
Pp. 569-574 |
D.C. Swinney
The ability for differentiated binding kinetics
to define irreversible or reversible states and
the impact of these differentiated states on a clinical
outcome is proposed here to contribute to the magnitude
of gastrointestinal toxicity observed with nonsteroidal
anti-inflammatory agents (NSAIDs). This example
and others highlight the potential for differentiated
binding kinetics to provide clinical differentiation. |
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| Moving in Silico Screening
into Practice: A Minimalist Approach to Guide Permeability
Screening!! Pp. 575-581 |
C.L. Stoner, M. Troutman, H.
Gao, K. Johnson, C. Stankovic, J. Brodfuehrer, E.
Gifford & M. Chang
This work focuses on the development and application
of an in silico passive permeability (Papp) model.
In addition, this work describes how this in silico
model can be used in combination with experimental
permeability screens such as PAMPA (Parallel Artificial
Membrane Permeability Assay) & MDCK (Madin Darby
Canine Kidney) cells to guide drug discovery while
saving resources. |
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| Circulating Oxidized Low-density
Lipoprotein (LDL) Induces Apoptosis and Stimulates Monocyte
Chemoattractant Protein-1 Expression in Cultured Endothelial
Cells Pp. 582-585 |
S. Yamagishi, T. Matsui, K.
Nakamura, K. Kawano & S. Kitano
The present results demonstrate that oxidized LDL
present in human plasma is pro-apoptotic and pro-inflmmatory
to ECs, thus suggesting the active participation
of plasma oxidized LDL in the process of atherosclerosis.
Our HPLC method for measuring plasma levels of oxidized
LDL may be useful to evaluate the efficacy of novel
therapeutics on atherosclerosis. |
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| Utilizing IL-12, IL-15 and IL-7
as Mucosal Vaccine Adjuvants Pp. 586-592 |
L. Stevceva, M. Moniuszko &
M.G. Ferrari
In this paper we review three of the most exciting
and promising cytokines for therapeutic intervention
and immunomodulation of immune responses: IL-12,
IL-15 and IL-7. Special emphasis is placed on the
effects of these cytokines on mucosal surfaces and
their utilization as mucosal vaccines adjuvants.useful
to evaluate the efficacy of novel therapeutics on
atherosclerosis. |
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