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Current
Medicinal Chemistry
ISSN: 0929-8673
Current Medicinal Chemistry
Volume 15, Number 3, 2008
Contents
Nanotubes at Neural and Immune Synapses Pp. 210-218
Larisa B. Goncharova and Alexander O. Tarakanov
[Abstract]
Endoradiotherapy with Peptides – Status
and Future Development Pp. 219-234
Uwe Haberkorn, Michael Eisenhut, Annette Altmann and Walter
Mier
[Abstract]
State of Art in 11C
Labelled Radiotracers Synthesis Pp. 235-277
M. Allard, E. Fouquet, D. James and M. Szlosek-Pinaud
[Abstract]
Nimesulide is a Selective COX-2 Inhibitory, Atypical
Non Steroidal Anti-Inflammatory Drug Pp. 278-283
H. Suleyman, E. Cadirci, A. Albayrak and Z. Halici
[Abstract]
Pharmacotherapies to Manage Bone Loss-Associated
Diseases: A Quest for the Perfect Benefit-to-Risk
Ratio Pp. 284-204
P. Valverde
[Abstract]
Bone Regeneration by Synthetic Octacalcium Phosphate
and its Role in Biological Mineralization Pp. 305-313
O. Suzuki, H. Imaizumi, S. Kamakura and T. Katagiri
[Abstract]
Abstracts
[Back to top]
Nanotubes at Neural and Immune Synapses
Larisa B. Goncharova and Alexander O. Tarakanov
This minireview aims to demonstrate that (i) natural
nanotubes play important roles in chemical signaling and (ii)
they represent one of the deep functional similarities between
neural and immune synapses. We also pay attention to the related
receptor assemblies and possibilities of chemically synthesized
carbon nanotubes to simulate functions of the natural ones.
[Back to top]
Endoradiotherapy with Peptides – Status and
Future Development
Uwe Haberkorn, Michael Eisenhut, Annette Altmann and Walter
Mier
With the advances in molecular biology and biochemistry
new imaging and treatment modalities based on the biological
prop-erties of tissues have been developed where important
progress has been achieved using antibodies and peptides.
This paper will concentrate on peptide vectors. When labeled
with therapeutic radioisotopes these agents are suitable for
endoradiotherapy and exploit the targeting potential for highly
specific treatment which has been realized for antibodies
against CD20 or peptides binding to somatostatin receptors.
This novel class of pharmaceuticals offers the potential to
develop specific therapies beyond the possibilities of current
chemotherapy and radiation therapy. Furthermore, these achievements
can be seen as proof of principle and encourage more research
towards the identification of new specifically binding molecules.
Activities towards the development of new biomolecules can
be based on biotechnology methods. Rational design uses informations
obtained from structure-activity relationship studies and
conformational analyses of peptide structures. This approach
relies on the identification of lead compounds and screening
of various derivatives of these compounds. In contrast to
rational design the central idea of black box approaches is
to create vast libraries of possible variants of molecules
and screen the population for the few compounds that show
the property of interest. The attracting feature relies on
the huge number of candidate molecules that can be used for
further evaluation. After the characterization of the structure-function
relationships for the lead compounds found in this process
further improvement by rational design of analogs can be performed.
[Back to top]
State of Art in 11C
Labelled Radiotracers Synthesis
M. Allard, E. Fouquet, D. James and M. Szlosek-Pinaud
Positron Emission Tomography has become a powerful scientific
and clinical tool probing biochemical processes in the human
body. Their clinical applications have proven to be vital
in the evaluation and diagnosis of diseases. This is due,
in large part, to advances in instrumentation and synthetic
chemistry. Carbon-11 is a valuable radionuclide in PET as
it virtually permits the synthesis of radiolabelled versions
of any compound of interest. The syntheses with carbon-11
present several features: limited number of labelled precursors,
sub-micromolar amounts of the starting materials, and a need
for the introduction of the radioisotope as late as possible
in the synthesis. All of these reasons have restricted complex
radiosyntheses. The short half-life of carbon-11 (20.4 min)
requires the rapid preparation and purification of carbon-11
labelled molecules. Those have to be carried out immediately
before use from cyclotron produced precursors ([11C]CO2,
[11C]CO,
[11C]CH4)
or reagents rapidly prepared from them ([11C]CH3I,
[11C]COCl2,
[11C]HCN).
As a consequence carbon-11 has been underused compared to
fluorine-18. However, because of the increasing molecular
complexity and diversity of bio-logically active compounds,
there is a need for new methodologies giving access in short
time and high yield to radioactive 11C-probes.
The aim of this review is to emphasize the methodologies used
in this field and to give a comprehensive overview of the
numerous advances, which occurred over the past decade. In
addition, for each labelling technique or reaction reported,
a special attention has been brought to classify the applications
in function of the targeted medical domain.
[Back to top]
Nimesulide is a Selective COX-2 Inhibitory, Atypical
Non-Steroidal Anti-Inflammatory Drug
H. Suleyman, E. Cadirci, A. Albayrak and Z. Halic
In this review it is shown that nimesulide, a selective
cyclooxigenase-2 (COX-2) inhibitor, is different from other
selective COX-2 inhibitors and classical non-steroidal anti-inflammatory
drugs (NSAIDs). The anti-inflammatory effect mechanism of
nimesulide (inhibition of inflammatory mediators) is similar
to other classic NSAIDs, but the protective effect of nimesulide
on classic NSAID-induced ulcers elucidates the difference
between nimesulide and these other drugs. It is known that
the selective COX-2 inhibitor nimesulide prevents NSAID-induced
ulcers, while celecoxib and rofecoxib, which are more selective
to COX-2, failed to prevent these ulcers. Nimesulide produces
gastro-protective effects via a completely different
mechanism. In addition, while selective COX-2 inhibitors increase
the risk for cardiovascular diseases, nimesulide does not
exert significant cardiotoxicity. This data suggests that
gastrointestinal side effects of classic NSAIDs cannot be
related to the COX-1 inhibition alone and also suggest that
nimesulide is an atypical NSAID, which is different from both
non-selective and selective COX-2 inhibitors.
[Back to top]
Pharmacotherapies to Manage Bone Loss-Associated Diseases:
A Quest for the Perfect Benefit-to-Risk Ratio
P. Valverde
In this review, benefits and side-effects of current
and emerging therapies to treat and prevent pathological bone
loss are described. Bisphosphonates are the antiresorptive
compounds most widely used in the treatment of bone-loss associated
diseases. They are generally well-tolerated although have
recently been associated with osteonecrosis of the jaw and
other complications. Therapies modulating estrogen receptor
activation are indicated in the prevention and treatment of
either breast cancer or osteoporosis in postmenopausal women.
Thus, hormone replacement therapy is effective in prevention
of osteoporosis, but its long-term use can increase the risk
of breast cancer, stroke and embolism. Tamoxifen benefits
all stages of breast cancer, but its use may lead to uterine
cancer and thromboembolism. Raloxifene is approved in prevention
of breast cancer and treatment of postmenopausal osteoporosis,
but its use can increase the risk of fatal stroke. Aromatase
inhibitors are superior to tamoxifen at advanced stages of
disease and as adjuvants, but their use increase fracture
incidence. Fulvestrant is as effective as aromatase inhibitors
in the treatment of advanced breast cancer and does not cause
bone fractures. Another antiresorptive available for the treatment
of postmenopausal osteoporosis, Paget’s disease and
hypercalcemia is calcitonin, which also exhibits analgesic
effects. A promising antiresorptive agent currently in clinical
trials is denosumab. Aditional therapies for osteoporosis
that decrease fracture risk consist of PTH-like anabolic agents
and the dual action bone agent strontium ranelate. Antiseptics
and antibiotics are used extensively in periodontal disease
intervention to target bacterial biofilm, although host-directed
therapies are also being developed.
[Back to top]
Bone Regeneration by Synthetic Octacalcium Phosphate
and its Role in Biological Mineralization
O. Suzuki, H. Imaizumi, S. Kamakura and T. Katagiri
Octacalcium phosphate (Ca8H2(PO4)6•5H2O;
OCP) has been advocated to be a precursor of biological apatite
crystals in bone and tooth. Recent studies, using physical
techniques, showed that OCP is present as a transient phase
during biological apatite formation in human dentin, porcine
enamel and murine bone. However, there is still a controversy
regarding the chemical nature of the first mineral formed
in the biominerals. A number of studies have demonstrated
that synthetic OCP shows bone regenerative and biodegradable
characteristics, rather than other calcium phosphate bone
substitute materials, such as hydroxyapatite (Ca10(PO4)6(OH)2
HA) ceramic. It seems likely that synthetic OCP may be an
alternative to autogenous bone graft. It is known that OCP
contains alternative layers of water molecules and an apatite
structure, and that the transition of OCP to HA is likely
to be spontaneous and irreversible. The conversion process
induces modification of local environment adjacent to OCP
surface, including the changes in adsorption of serum proteins
and concentration of calcium and inorganic phosphate ions.
This article reviews the possible application to bone regeneration
by synthetic OCP and the mechanism to enhance bone regeneration
in relation to biological mineralization in bone and tooth.
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