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Mini-Reviews
in Medicinal Chemistry
ISSN: 1389-5575
Mini-Reviews in Medicinal
Chemistry
Volume 5, Number 11, November 2005
Contents
Second-Generation KATP Channel Openers
Pp. 961-969
Raimund Mannhold and Gérard Leclerc
[Abstract]
Natural Products as Angiogenesis Modulators
Pp. 971-993
K.A. El Sayed
[Abstract]
Are Vanadium Compounds Drugable? Structures
and Effects of Antidiabetic Vanadium Compounds: A Critical
Review Pp. 995-1008
Thomas Scior, Antonio Guevara-García, Philippe
Bernard, Quoc-Tuan Do, David Domeyer and Stefan Laufer
[Abstract]
New Fluoroquinolones: A Class of Potent
Antibiotics Pp. 1009-1017
Marcus Vinícius Nora De Souza
[Abstract]
Non-Insulin Dependent Diabetes Mellitus:
Present Therapies and New Drug Targets Pp.1019
Saibal Kumar Das and Ranjan Chakrabarti
[Abstract]
1,2,4,5-Tetraoxacycloalkanes: Synthesis
and Antimalarial Activity Pp.1035
A. Masuyama, J.-M. Wu, M. Nojima, H.-S. Kim and Y. Wataya
[Abstract]
Knowledge-Driven Lead Discovery Pp.1045
Bernard Pirard
[Abstract]
Abstracts
[Back to top]
Second-Generation KATP Channel Openers
Raimund Mannhold and Gérard Leclerc
This review discusses structural aspects of second-generation
KATP channel openers (KCOs), which exhibit improved
tissue-selectivity. Their therapeutic profile is debated with
main focus on cardiac ischemia, asthma, and urinary incontinence.
[Back to top]
Natural Products as Angiogenesis Modulators
K.A. El Sayed
Cancer remains one of the major causes of death worldwide.
Anti-angiogenic therapy is one of the new approaches to anticancer
therapy. Out of 22 angiogenesis inhibitors currently under
clinical trials there are 11 natural products or were modeled
on a natural product parent. This review shows the potential
of natural products for the discovery of new anti-angiogenic
leads.
[Back to top]
Are Vanadium Compounds Drugable? Structures and Effects of
Antidiabetic Vanadium Compounds: A Critical Review
Thomas Scior, Antonio Guevara-García, Philippe
Bernard, Quoc-Tuan Do, David Domeyer and Stefan Laufer
Vanadate can be bioequivalent to phosphate and replace it
in cellular metabolism. The detection of insulin-like activity
has spurred interest in the development of oral anti-diabetic
drugs containing vanadium. We collected and evaluated a vast
toxicity data set and discussed molecular aspects related
to insulin-mimetic effects of vanadium complexes.
[Back to top]
New Fluoroquinolones: A Class of Potent Antibiotics
Marcus Vinícius Nora De Souza
The discovery of antibiotics opened a new era in the treatment
against several pathogenic microorganisms that can disable
or kill humans. The appearance of the fluoroquinolones (based
on nalidixic acid, 4-quinolone-3-carboxylates), in the early
1980`s, gave a new impetus in the treatment of infectious
diseases. Despite these favourable properties, the earlier
fluoroquinolones had limited potency against some clinically
important organisms, especially Gram-positive pathogens so
that the development of resistance to these organisms has
become a serious problem. Thus the development of new fluoroquinolones
with a better pharmacokinetic profile, potency, broad spectrum
of activity, solubility, prolonged serum half-life and oral
and parenteral routes of administration has been a major focus
on recent research. The increasing interest in this class
led me to review the promising new fluoroquinolones in clinical
trials.
[Back to top]
Non-Insulin Dependent Diabetes Mellitus: Present Therapies
and New Drug Targets
Saibal Kumar Das and Ranjan Chakrabarti
Type 2 Diabetes Mellitus (DM) or Non-Insulin Dependent Diabetes
Mellitus (NIDDM) accounts for 90-95% of all diabetes cases
and has become a major health concern over the years. This
disease has assumed frightening proportions due to unhealthy
food habits and sedentary life style. About a decade ago,
due to the absence of defined molecular targets or an understanding
of disease pathophysiology, treatment of this disease was
mostly focused on insulin secretion or administration of external
insulin. During the past decade however, advent of genomics
and proteomics has helped in understanding the molecular alteration
characteristics of NIDDM. Untreated type 2 diabetes leads
to several complications such as hyperlipidemia, hypertension
and atherosclerosis – collectively known as Syndrome
X. Though United Kingdom Prospective Diabetes Study (UKPDS)
showed that normalization of hyperglycemia could prevent majority
of diabetes complications, the available treatment regime
does not adequately normalize the blood glucose level in type
2 diabetic patients. Currently, four distinct classes of oral
hypoglycemic agents are available, some of which can act as
lipid lowering agents as well. The efficacy and side effect
profiles of these drugs are still to be optimized, so there
is an unmet need for better candidates. Several new targets
as well as better drugs for old targets are under investigation
across the world. Availability of such drugs, based on the
validated targets, may lead to a new therapeutic paradigm
for the prevention of diabetes as well as complications arising
out of it. The current review will deal with existing oral
therapies for type 2 diabetes as well as the emerging therapeutic
targets.
[Back to top]
1,2,4,5-Tetraoxacycloalkanes: Synthesis and Antimalarial Activity
A. Masuyama, J.-M. Wu, M. Nojima, H.-S. Kim and Y. Wataya
In this short review the methods of preparation of novel
1,2,4,5-tetraoxacycloalkanes and the related peroxides are
summarized, with the emphasis on the usefulness of 1,1-bishydroperoxides
as the precursor. Also, their antimalarial activities in
vitro and in vivo are discussed.
[Back to top]
Knowledge-Driven Lead Discovery
Bernard Pirard
Virtual screening encompasses several computational approaches
which have proven valuable for identifying novel leads. These
approaches rely on available information. Herein, we review
recent successful applications of virtual screening. The extension
of virtual screening methodologies to target families is also
briefly discussed.
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