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Mini-Reviews
in Medicinal Chemistry
ISSN: 1389-5575
Mini-Reviews in Medicinal
Chemistry
Volume 9, Number 3, March 2009
Contents
Linear Naphtho-γ-Pyrones:
A Naturally Occurring Scaffold of Biological Importance Pp.
273-292
R.A. Barrow and M.W.B. McCulloch
[Abstract] [Purchase
Article] [PMID:
19275720 PubMed - indexed for MEDLINE]
Antimicrobial, In Vitro and In Vivo
Antineoplastic Activities, Mechanism of Action, Structural
and Thermal Properties of a Small-Novel Pharmaceutical Organometallic
Chelate Pp. 293-299
Kareem I. Batarseh
[Abstract] [Purchase
Article] [PMID:
19275721 PubMed - indexed for MEDLINE]
Screening of Dipeptides Having Central
Functions for Excitation and Sedation Pp. 300-305
H. Yamane, D.M. Denbow and M. Furuse
[Abstract] [Purchase
Article] [PMID:
19275722 PubMed - indexed for MEDLINE]
New Insight in LPS Antagonist Pp.
306-317
A. Ianaro, M. Tersigni and F. D’Acquisto
[Abstract] [Purchase
Article] [PMID:
19275723 PubMed - indexed for MEDLINE]
The Role of WNT in Rheumatoid Arthritis
and its Therapeutic Implication Pp. 318-323
Kazushi Imai, Tadashige Chiba, Genta Maeda and
Masako Morikawa
[Abstract] [Purchase
Article] [PMID:
19275724 PubMed - indexed for MEDLINE]
Future Targets in Endometriosis Treatment:
Targeting the Endometriotic Implant Pp. 324-328
Warren B. Nothnick and Xuan Zhang
[Abstract] [Purchase
Article] [PMID:
19275725 PubMed - indexed for MEDLINE]
Oligomerization of the Heptahelical G
Protein Coupling Receptors: A Case for Association Using Transmembrane
Helices Pp. 329-339
M.S. Parker, R. Sah, E.A. Park, T. Sweatman,
A. Balasubramaniam, F.R. Sallee and S.L. Parker
[Abstract] [Purchase
Article] [PMID:
19275726 PubMed - indexed for MEDLINE]
Microwave Assisted Synthesis: A New Technology
in Drug Discovery Pp. 340-358
V. Santagada, F. Frecentese, E. Perissutti, F.
Fiorino, B. Severino and G. Caliendo
[Abstract] [Purchase
Article] [PMID:
19275727 PubMed - indexed for MEDLINE]
Novel Perspectives in Celiac Disease
Therapy Pp. 359-367
Yolanda Sanz
[Abstract] [Purchase
Article] [PMID:
19275728 PubMed - indexed for MEDLINE]
Lysophospholipids: Their Generation,
Physiological Role and Detection. Are They Important Disease
Markers? Pp. 368-378
Beate Fuchs and Jürgen Schiller
[Abstract] [Purchase
Article] [PMID:
19275729 PubMed - indexed for MEDLINE]
Role of the HIV-1 Positive Elongation
Factor P-TEFb and Inhibitors Thereof Pp. 379-385
Yan Wang, Xin-yong Liu and Erik De Clercq
[Abstract] [Purchase
Article] [PMID:
19275730 PubMed - indexed for MEDLINE]
Physiological and Pathophysiological
Functions of SIRT1 Pp. 386-394
M. Wojcik, K. Mac-Marcjanek and L.A. Wozniak
[Abstract] [Purchase
Article] [PMID:
19275731 PubMed - indexed for MEDLINE]
New Approaches to Target the Androgen
Receptor and STAT3 for Prostate Cancer Treatments Pp.
395-400
Meilan He and Charles Y.F. Young
[Abstract] [Purchase
Article] [PMID:
19275732 PubMed - indexed for MEDLINE]
Abstracts
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[Purchase
Article] [PMID:
19275720 PubMed - indexed for MEDLINE]
Linear Naphtho-γ-Pyrones:
A Naturally Occurring Scaffold of Biological Importance
R.A. Barrow and M.W.B. McCulloch
The linear naphtho-γ-pyrone
(LNGP) moiety is a naturally occurring scaffold with broad
biological activity ranging through antimicrobial, antiviral,
insecticidal and anti-estrogenic activity. This review, the
first of its kind, surveys the chemical literature in an effort
directed toward assembling data that will facilitate the construction
of activity profiles associated with this emerging class of
compounds. The structural and associated biological information
has been presented in tabular format with all structures revealed
throughout the document and referencing that will allow the
reader to rapidly access the literature pertaining to a specific
activity or structural class.
[Back to top]
[Purchase
Article] [PMID:
19275721 PubMed - indexed for MEDLINE]
Antimicrobial, In Vitro and In Vivo Antineoplastic
Activities, Mechanism of Action, Structural and Thermal Properties
of a Small-Novel Pharmaceutical Organometallic Chelate
Kareem I. Batarseh
The antimicrobial, the in vitro and in vivo
antineoplastic activities, mechanism of action, the structural
and thermal properties of a pharmaceutically novel and small
organometallic silver (I)-tartaric acid complex synthesized
by the author given the title name Aliargentumycine or AAgM
are reviewed here.
[Back to top]
[Purchase
Article] [PMID:
19275722 PubMed - indexed for MEDLINE]
Screening of Dipeptides Having Central Functions for Excitation
and Sedation
H. Yamane, D.M. Denbow and M. Furuse
:The naturally-occurring dipeptide carnosine (β-alanyl-L-histidine)
and the tripeptide glutathione (L-γglutamyl-L-cysteinylglycine)
are found extensively in animal tissues such as brain and
skeletal muscle. Central functions for excitation and sedation
of them and their derivatives were screened.
[Back to top]
[Purchase
Article] [PMID:
19275723 PubMed - indexed for MEDLINE]
New Insight in LPS Antagonist
A. Ianaro, M. Tersigni and F. D’Acquisto
Lipopolysaccharide (LPS) or endotoxin, the major constituent
of the outer membrane of Gram negative bacteria, has been
implicated as the bacterial product responsible for the clinical
syndrome of sepsis. LPS binding to the host receptor Toll-like
receptor 4 (TLR4) triggers an inflammatory reaction characterised
by the release of large number of inflammatory mediators that
allow the host to respond to the invading pathogen. When this
production becomes uncontrolled and excessive, it leads to
the development of septic shock. Despite decades of efforts
in supporting therapies, sepsis remains the leading cause
of death amongst critically ill patients. Unfortunately, the
major factor contributing to the high morbidity and mortality
of sepsis is the lack of the effective targeted treatment.
Indeed, over 30 drugs for the treatment of sepsis have been
developed: many of these target specific inflammatory mediators
and have thus been, in general, unsuccessful since sepsis
relies on the cross talk of several cytokines and the block
of a single factor has been proven to be ineffective. More
successful strategies include those modulating the early phase
of LPS signalling such as the ones that prevent the binding
of LPS to host cells and the subsequent cascade of detrimental
events. In this light, effective LPS an-tagonists would represent
invaluable tools to efficaciously manage sepsis. This review
discusses the evolution of naturally occurring and synthetic
LPS antagonists with emphasis on the development of several
natural new molecules.
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[Purchase
Article] [PMID:
19275724 PubMed - indexed for MEDLINE]
The Role of WNT in Rheumatoid Arthritis and its Therapeutic
Implication
Kazushi Imai, Tadashige Chiba, Genta Maeda and
Masako Morikawa
Rheumatoid arthritis (RA) is a systematic inflammatory
and intractable disease, which progressively affects multiple
joints. Recent findings strongly suggest a key role of WNT
signaling in the disease initiation and progression. In this
review, we discuss the role and possibility of treatment by
targeting WNT signaling.
[Back to top]
[Purchase
Article] [PMID:
19275725 PubMed - indexed for MEDLINE]
Future Targets in Endometriosis Treatment: Targeting the Endometriotic
Implant
Warren B. Nothnick and Xuan Zhang
Endometriosis is an enigmatic, debilitating disease which
affects as many as 15% of all women of reproductive age and
is characterized by pelvic pain and infertility. Current treatment
regimes used to manage the disease do so by inducing a hypoestrogenic
state. While the absence of circulating estrogen levels lead
to a regression of the disease, this hypoestrogenism also
induces many unpleasant side-effects. As such, these and other
shortcomings of current drug therapies emphasize their limitations
and the necessity for the development of novel endometriosis
treatments. In this review, current therapies which target
the biochemistry of the implant are discussed with emphasis
on aromatase inhibitors, anti-angiogenic compounds and vascular-disrupting
agents.
[Back to top]
[Purchase
Article] [PMID:
19275726 PubMed - indexed for MEDLINE]
Oligomerization of the Heptahelical G Protein Coupling Receptors:
A Case for Association Using Transmembrane Helices
M.S. Parker, R. Sah, E.A. Park, T. Sweatman,
A. Balasubramaniam, F.R. Sallee and S.L. Parker
The heptahelical G protein coupling receptors oligomerize
extensively via transmembrane domains, in association
with heterotrimeric G proteins. This provides higher affinity
for agonists, conformational stability necessary for signal
transduction, and protection from intracellular proteinases.
The oligomerization is relevant to organismic pathophysiology
and could be targeted by natural or modified agonists.
[Back to top]
[Purchase
Article] [PMID:
19275727 PubMed - indexed for MEDLINE]
Microwave Assisted Synthesis: A New Technology in Drug Discovery
V. Santagada, F. Frecentese, E. Perissutti, F.
Fiorino, B. Severino and G. Caliendo
The interest in the microwave assisted organic synthesis
has been growing during the recent years. It results from
an increasing knowledge of fundamentals of the dielectric
heating theory, availability of an equipment designed especially
for the laboratory use as well as the discovery of the special
techniques of the microwave syntheses. The efficiency of microwave
flash-heating chemistry in dramatically reducing reaction
times (reduced from days and hours to minutes and seconds)
has recently been proven in several different fields of organic
chemistry and this aspect is of great importance in high-speed
combinatorial and medicinal chemistry. In this contribution,
the current state of the art is summarized providing examples
of the most recent applications in the field of microwave
assisted synthesis of biologically active compounds both in
heterocyclic and in peptide and peptidomimetic optimization.
[Back to top]
[Purchase
Article] [PMID:
19275728 PubMed - indexed for MEDLINE]
Novel Perspectives in Celiac Disease Therapy
Yolanda Sanz
Currently the only treatment for celiac disease is adherence
to a strict gluten-free diet; however, compliance with this
diet is complex and other alternatives are called for. Herein,
we review recent developments in the design of novel therapeutic
strategies to counteract the pathogenic effects of the interactions
between gluten peptides and their specific biological targets.
[Back to top]
[Purchase
Article] [PMID:
19275729 PubMed - indexed for MEDLINE]
Lysophospholipids: Their Generation, Physiological Role and
Detection. Are They Important Disease Markers?
Beate Fuchs and Jürgen Schiller
The concentration of lysophospholipids (LPL) increases
under pathological conditions and, thus, LPL attract diagnostic
and pharmacological interest. LPL are particularly interesting
because they possess pro- and anti-inflammatory properties
and can be generated by phospholipases and reactive oxygen
species (ROS).
This review provides an overview of the mechanisms by which
LPL are generated and how they can be determined. The effects
of LPL as signaling molecules and their roles in different
pathologies are discussed. The focus will be on lysophosphatidylcholine
(LPC).
[Back to top]
[Purchase
Article] [PMID:
19275730 PubMed - indexed for MEDLINE]
Role of the HIV-1 Positive Elongation Factor P-TEFb and Inhibitors
Thereof
Yan Wang, Xin-yong Liu and Erik De Clercq
Transcription is considered to be a crucial step in the
replication cycle of HIV-1. Tat regulates an early step of
transcription elongation. The positive elongation factor P-TEFb,
a heterodimer containing a catalytic subunit (CDK9) and unique
regulatory cyclins (CycT1), is required for HIV-1 Tat transcriptional
activation. This is a potential target for new HIV-1 transcription
inhibitors. Without P-TEFb, transactivation is restrained
and only short transcripts are generated. All the P-TEFb inhibitors
can suppress the HIV-1 transactivation process by inhibition
of CycT1, CDK9 or their interaction. Several low-molecular-weight
compounds such as flavopiridol, roscovitine and the human
small nuclear RNA 7SK which have been showed to possess potent
anti-HIV activity by interfering with P-TEFb functions are
reviewed in this article.
[Back to top]
[Purchase
Article] [PMID:
19275731 PubMed - indexed for MEDLINE]
Physiological and Pathophysiological Functions of
SIRT1
M. Wojcik, K. Mac-Marcjanek and L.A. Wozniak
The human SIRT1 is a nuclear enzyme from the class III histone
deacetylases (HDACs) which is widely distributed in mammalian
tissues. A variety of SIRT1 substrates hints that this protein
is involved in the regulation of diverse biological processes,
including cell survival, apoptosis, gluconeogenesis, adipogenesis,
lipolysis, stress resistance, muscle differentiation, and
insulin secretion. This review emphasizes catalytic properties
of SIRT1 and its role in apoptosis, insulin pathway, and neuron
survival.
[Back to top]
[Purchase
Article] [PMID:
19275732 PubMed - indexed for MEDLINE]
New Approaches to Target the Androgen Receptor and STAT3 for
Prostate Cancer Treatments
Meilan He and Charles Y.F. Young
Prostate cancer (PCa) is a common cause of death in men and
remains incurable in the androgen-refractory phase. Growing
evidence has shown that the androgen receptor (AR) and signal
transducers and activators of transcription 3 (STAT3) could
be effective targets for androgen-refractory PCa therapy.
Many strategies have been reported to inhibit the AR or STAT3
activities. In this review, we focus on the AR N-terminal
domain and AR chaperones, as well as small molecule inhibitors
to STAT3 with which we discuss some new approaches to target
the AR and STAT3 as potential treatments for androgen-refractory
PCa.
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