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Mini-Reviews
in Medicinal Chemistry
ISSN: 1389-5575
Mini-Reviews in Medicinal
Chemistry
Volume 9, Number 9, August 2009
Contents
GSK3 Inhibitors and Disease Pp. 1024-1029
Félix Hernández, Javier Díaz
Nido, Jesús Avila and Nieves Villanueva
[Abstract][Purchase
Article][PMID:
19689399 PubMed - indexed for MEDLINE]
Pleiotropic, Cardioprotective Effects of Omega-3 Polyunsaturated
Fatty Acids Pp. 1030-1039
Pawel Petkow Dimitrow and Marek
Jawien
[Abstract] [Purchase
Article][PMID:
19689400 PubMed - indexed for MEDLINE]
Chemistry and Biology of Landomycins, an Expanding Family
of Polyketide Natural Products Pp. 1040-1051
B. Ostash, A. Korynevska, R. Stoika and
V. Fedorenko
[Abstract] [Purchase
Article][PMID:
19689401 PubMed - indexed for MEDLINE]
The Use of Intravenous Aminobisphosphonates for the Treatment
of Paget's Disease of Bone Pp. 1052-1063
Luigi Gennari, Daniela Merlotti, Giuseppe
Mossetti, Domenico Rendina, Vincenzo De Paola, Giuseppe Martini
and Ranuccio Nuti
[Abstract] [Purchase
Article][PMID:
19689402 PubMed - indexed for MEDLINE]
Control of Tumor Markers Using Nanotechnology Pp.
1064-1074
A. Gómez-Hens, J.M. Fernández-Romero
and M.P. Aguilar-Caballos
[Abstract] [Purchase
Article][PMID:
19689403 PubMed - indexed for MEDLINE]
Structural Basis for the Design of PPAR-γ
Ligands: A Survey on Quantitative Structure- Activity Relationships
Pp. 1075-1083
Costas Giaginis, Stamatios Theocharis
and Anna Tsantili-Kakoulidou
[Abstract] [Purchase
Article][PMID:
19689404 PubMed - indexed for MEDLINE]
HIF-1α
Modulates Energy Metabolism in Cancer Cells by Inducing Over-Expression
of Specific Glycolytic Isoforms Pp. 1084-1101
Alvaro Marín-Hernández, Juan
C. Gallardo-Pérez, Stephen J. Ralph, Sara Rodríguez-Enríquez
and Rafael Moreno-Sánchez
[Abstract] [Purchase
Article][PMID:
19689405 PubMed - indexed for MEDLINE]
ABC Transporters as Potential Targets for Modulation of Drug
Resistance Pp. 1102-1112
L. Gatti, G.L. Beretta, G. Cossa, F. Zunino
and P. Perego
[Abstract] [Purchase
Article][PMID:
19689406 PubMed - indexed for MEDLINE]
Pharmacological Options for Treatment of Hyperandrogenic Disorders Pp. 1113-1126
P. Reismann, I. Likó, P. Igaz, A.
Patócs and K. Rácz
[Abstract] [Purchase
Article][PMID:
19689407 PubMed - indexed for MEDLINE]
Treating Age-Related Macular Degeneration – Interaction
of VEGF-Antagonists with their Target Pp.
1127-1135
A. Klettner and J. Roider
[Abstract] [Purchase
Article][PMID:
19689408 PubMed - indexed for MEDLINE]
Forms of Iron Binding in the Cells and the Chemical Features
of Chelation Therapy Pp. 1136-1146
S. Puntarulo and M. Galleano
[Abstract] [Purchase
Article][PMID:
19689409 PubMed - indexed for MEDLINE]
Abstracts
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[Purchase
Article][PMID:
19689399 PubMed - indexed for MEDLINE]
GSK3 Inhibitors and Disease
Félix Hernández, Javier Díaz
Nido, Jesús Avila and Nieves Villanueva
This review describes, briefly, the characteristics and
regulation of glycogen synthase kinase 3 (GSK3) together with
the role of GSK3 dysfunctions in different pathologies, and
GSK3 as target for therapeutic treatment in different diseases.
Several GSK3 inhibitors acting at different levels are described
in this work, ranging from cations like lithium to small compounds
developed by different pharmaceutical companies. Also, the
use of specific interference RNA (iRNA) for the specific inhibition
of the expression of the different GSK3 isoforms is discussed.
[Back to top]
[Purchase
Article][PMID:
19689400 PubMed - indexed for MEDLINE]
Pleiotropic, Cardioprotective Effects of Omega-3 Polyunsaturated
Fatty Acids
Pawel Petkow Dimitrow and Marek
Jawien
The cardioprotective effects of food rich in omega-3
(ω-3)
polyunsaturated fatty acids (PUFA) on cardiovascular risk
has been of interest from the moment when a low rate of coronary
heart disease was documented in the Eskimo population. The
aim of the present review is to discuss recent studies documenting
multidirectional action of ω-3
PUFA due to its pleiotropic properties. Experimental studies
in cellular and animal models have extensively documented
the favorable effects of ω-3
PUFA (eicosapentaenoic acid and docosahexaenoic acid) on:
inflammatory processes, endothelial dysfunction, platelet
aggregation and arrhythmogenesis. It was reported that antiarrhythmic
effects of ω-3
PUFA resulted from stabilization of cardiomyocyte membrane
and inhibition of ion channels. Moreover, PUFA possess several
pleiotropic properties i.e. anti-inflammatory, anti-atherogenic
and antithrombotic. Anti-atherogenic effects (plaque stabilization)
of ω-3
PUFA have recently been demonstrated. It was documented (OCEAN
study) that eicosapentaenoic acid from a source of highly
purified ethyl esters is incorporated into plaques in a relatively
short period of time and these higher concentrations of ω-3
PUFA may stabilize vulnerable atherosclerotic plaques. The
anti-inflammatory effect of ω-3
PUFA is associated with reduction of levels of TNF-α
and interleukin-6. Eicosapentaenoic acid and docosahexaenoic
acid inhibit arachidonic acid metabolism to inflammatory eicosanoids.
[Back to top] [Purchase
Article][PMID:
19689401 PubMed - indexed for MEDLINE]
Chemistry and Biology of Landomycins, an Expanding Family
of Polyketide Natural Products
B. Ostash, A. Korynevska, R. Stoika and
V. Fedorenko
This review covers existing literature (from 1990 to
2008) on landomycins (LS), a family of glycosylated
angucyclines, with an emphasis on the bioactivity scope of
landomycin (La)-like structures accessible
via biocombinatorial manipulations. Some LS
display strong antitumor activity and have inspired several
chemical studies focused mainly on their unusual deoxysugar
chains. A decade of genetic studies on La-producing
bacteria has provided many novel molecules with altered structure
and activity. A complex nonlinear correlation between the
length of the carbohydrate tail of LS and
their antitumor activity has also been revealed. It implies
that simpler LS than the largest member of
the family, LaA, are still potential drug
leads. Combinatorial biosynthesis appears to be a powerful
tool to search the chemical space around the La
scaffold.
[Back to top] [Purchase
Article][PMID:
19689402 PubMed - indexed for MEDLINE]
The Use of Intravenous Aminobisphosphonates for the Treatment
of Paget's Disease of Bone
Luigi Gennari, Daniela Merlotti, Giuseppe
Mossetti, Domenico Rendina, Vincenzo De Paola, Giuseppe Martini
and Ranuccio Nuti
Paget’s disease of bone is a focal skeletal disorder
characterized by the formation of structurally abnormal bone,
deformity and other complications leading to significant disability
and bone pain. Recently, the availability of newer, more potent
nitrogen-containing bisphosphonates has improved treatment
outcomes, allowing a more effective and convenient management
of this disorder.
[Back to top] [Purchase
Article][PMID:
19689403 PubMed - indexed for MEDLINE]
Control of Tumor Markers Using Nanotechnology
A. Gómez-Hens, J.M. Fernández-Romero
and M.P. Aguilar-Caballos
The relevance of tumor markers in clinical diagnosis
of cancer has given rise to the development of new approaches
based on the use of nanoparticles to improve the features
of the immunoassays developed for their control. This article
reviews the usefulness of different nanoparticles to develop
direct, sandwich and competitive assays for the individual
and multiplexed determination of these compounds.
[Back to top] [Purchase
Article][PMID:
19689404 PubMed - indexed for MEDLINE]
Structural Basis for the Design of PPAR-γ
Ligands: A Survey on Quantitative Structure- Activity Relationships
Costas Giaginis, Stamatios Theocharis
and Anna Tsantili-Kakoulidou
The present review after providing a short overview on
PPARs and their pleiotropic action focuses on the QSAR studies
reported mainly for PPAR-γ
agonists. The different 3D and 2D QSAR models are discussed,
their impact in better understanding of the mechanism of action
is analyzed and their contribution in the design of new molecules
is outlined.
[Back to top] [Purchase
Article][PMID:
19689405 PubMed - indexed for MEDLINE]
HIF-1α
Modulates Energy Metabolism in Cancer Cells by Inducing Over-Expression
of Specific Glycolytic Isoforms
Alvaro Marín-Hernández, Juan
C. Gallardo-Pérez, Stephen J. Ralph, Sara Rodríguez-Enríquez
and Rafael Moreno-Sánchez
To develop new and more efficient anti-cancer strategies
it will be important to characterize the products of transcription
factor activity essential for tumorigenesis. One such factor
is hypoxia-inducible factor-1α
(HIF-1α),
a transcription factor induced by low oxygen conditions and
found in high levels in malignant solid tumors, but not in
normal tissues or slow-growing tumors. In fast-growing tumors,
HIF-1α
is involved in the activation of numerous cellular processes
including resistance against apoptosis, over-expression of
drug efflux membrane pumps, vascular remodeling and angiogenesis
as well as metastasis. In cancer cells, HIF-1α
induces over-expression and increased activity of several
glycolytic protein isoforms that differ from those found in
non-malignant cells, including transporters (GLUT1, GLUT3)
and enzymes (HKI, HKII, PFK-L, ALD-A, ALD-C, PGK1, ENO-α,
PYK-M2, LDH-A, PFKFB-3). The enhanced tumor glycolytic flux
triggered by HIF-1α
also involves changes in the kinetic patterns of expressed
isoforms of key glycolytic enzymes. The HIF-1α
induced isoforms provide cancer cells with reduced sensitivity
to physiological inhibitors, lower affinity for products and
higher catalytic capacity (Vmaxf) in forward
reactions because of marked over-expression compared to those
isoforms expressed in normal tissues. Some of the HIF1α-induced
glycolytic isoforms also participate in survival pathways,
including transcriptional activation of H2B histone (by LDH-A),
inhibition of apoptosis (by HKII) and promotion of cell migration
(by ENO-α).
HIF-1α
action may also modulate mitochondrial function and oxygen
consumption by inactivating the pyruvate dehydrogenase complex
in some tumor types, or by modulating cytochrome c oxidase
subunit 4 expression to increase oxidative phosphorylation
in other cancer cell lines. In this review, the roles of HIF-1α
and HIF1α-induced
glycolytic enzymes are examined and it is concluded that targeting
the HIF1α-induced
glucose transporter and hexokinase, important to glycolytic
flux control, might provide better therapeutic targets for
inhibiting tumor growth and progression than targeting HIF1α
itself.
[Back to top] [Purchase
Article][PMID:
19689406 PubMed - indexed for MEDLINE]
ABC Transporters as Potential Targets for Modulation of Drug
Resistance
L. Gatti, G.L. Beretta, G. Cossa, F. Zunino
and P. Perego
ATP binding cassette transporters are implicated in multidrug
resistant phenotypes of tumor cells and may be cancer stem
cell markers. Inhibitors of drug efflux pumps represent an
emerging group of potentially useful agents for the improvement
of antitumor therapy. Here we provide an overview of drug
transporter functions and modulation.
[Back to top] [Purchase
Article][PMID:
19689407 PubMed - indexed for MEDLINE]
Pharmacological Options for Treatment of Hyperandrogenic Disorders
P. Reismann, I. Likó, P. Igaz, A.
Patócs and K. Rácz
Hyperandrogenic disorders are frequent in women. The
most common cause is polycystic ovary syndrome, a condition
found up to 7% in women of reproductive age. The effects of
testosterone and dihydrotestosterone are elicited via
androgen receptors. Androgen receptor acts as a ligand-dependent
transcription factor that regulates the expression of several
target genes. There are several pharmacological possibilities
for the treatment of androgen excess, as inhibition of the
biologic activity of androgens can be carried out at different
levels. The androgen receptor, the 5α-reductase
enzyme, and the hypothalamic-pituitary-gonad axis are the
most frequent targets of antiandrogenic therapies. This review
summarizes the structural and chemical features of currently
available antiandrogenic drugs, including cyproterone acetate,
spironolactone, flutamide and finasteride. Also, it presents
some recent advances in the chemistry and pharmacology of
novel steroidal and non-steroidal antiandrogens, and 5α-reductase
inhibitors. Finally, recent knowledge on non-classical antiandrogenic
drugs, such as insulin-sensitizers, ketoconazole, and GnRH-agonists
are briefly discussed.
[Back to top] [Purchase
Article][PMID:
19689408 PubMed - indexed for MEDLINE]
Treating Age-Related Macular Degeneration – Interaction
of VEGF-Antagonists with their Target
A. Klettner and J. Roider
The neutralization of VEGF is the current treatment of
choice for age-related macular degeneration. Current approaches
include anti-VEGF-antibodies and –Fab Fragments, aptamers,
soluble receptors (Traps) and siRNA. The molecular properties
of VEGF and its antagonists are reviewed and the pathways
of action of these substances are discussed.
[Back to top] [Purchase
Article][PMID:
19689409 PubMed - indexed for MEDLINE]
Forms of Iron Binding in the Cells and the Chemical Features
of Chelation Therapy
S. Puntarulo and M. Galleano
Iron is essential for human life, however it can be toxic
through Fe ability to generate oxygen-derived radicals. This
work reviews the main features of Fe binding in the cell and
its association to these processes. The chemical nature of
the Fe extracted by chelation therapy in pathophysiological
situations is also analyzed.
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