| Mini-Reviews
in Medicinal Chemistry
ISSN: 1389-5575
Mini-Reviews in Medicinal
Chemistry
Volume 5, Number 1, January 2005
Contents
Recent Progress in Structure Activity Relationship
and Mechanistic Studies of Taxol Analogues Pp.1-12
W.-S. Fang and X.-T. Liang
[Abstract]
Medicinal Chemistry, Metabolic Profiling
and Drug Target Discovery: A Role for Metabolic Profiling
in Reverse Pharmacology and Chemical Genetics Pp.13-20
George G. Harrigan, Daniel J. Brackett and Laszlo G. Boros
[Abstract]
The Highly Specific Carbohydrate-Binding Protein
Cyanovirin-N: Structure, Anti-HIV/Ebola Activity and Possibilities
for Therapy Pp.21-31
Laura G. Barrientos and Angela M. Gronenborn
[Abstract]
Inflammation in Atherosclerosis: New Opportunities
for Drug Discovery Pp.33-40
Charles Q. Meng
[Abstract]
Peptide-Oligonucleotide Hybrids in Antisense Therapy
Pp.41-55
Tracie L. Pierce, Anthony R. White, Geoffrey W. Tregear
and Patrick M. Sexton
[Abstract]
Pharmacological Properties of Furoxans and Benzofuroxans:
Recent Developments Pp.57-71
Hugo Cerecetto and Williams Porcal
[Abstract]
Lactones: Generic Inhibitors of Enzymes? Pp.73-95
Monika I. Konaklieva and Balbina J. Plotkin
[Abstract]
Involvement of Cannabinoids in Cellular Proliferation
Pp.97-106
Maria L. Lopez-Rodriguez, Alma Viso, Silvia Ortega-Gutierrez
and Ines Diaz-Laviada
[Abstract]
Abstracts
[Back to top]
Recent Progress in Structure Activity Relationship
and Mechanistic Studies of Taxol Analogues
W.-S. Fang and X.-T. Liang
Structure activity relationship (SAR) and mechanism of paclitaxel
and its analogues in recent years are discussed in the following
areas: SAR of paclitaxel analogues toward “normal”
and multi-drug resistance tumors; paclitaxel prodrugs with
improved water solubitily and specificity; mechanism of paclitaxel
related to tubulin binding and quest for its pharmacophore.
[Back to top]
Medicinal Chemistry, Metabolic Profiling and Drug Target Discovery:
A Role for Metabolic Profiling in Reverse Pharmacology and
Chemical Genetics
George G. Harrigan, Daniel J. Brackett and Laszlo
G. Boros
Comprehensive analysis of the metabolome can contribute to
mechanism of action studies for small molecules discovered
in phenotypic screens. Examples are presented in this overview
of the rapidly developing field of “metabolic profiling.”
These examples include the use of NMR in gene function analysis,
GC-based studies on the identification of metabolic pathways
affected by PPAR-γ
agonists, applications of Fourier-transform MS and the use
of stable isotope-based metabolic profiling (SIDMAP) to investigate
metabolic adaptive changes induced by effective anticancer
agents.
[Back to top]
The Highly Specific Carbohydrate-Binding Protein
Cyanovirin-N: Structure, Anti-HIV/Ebola Activity and Possibilities
for Therapy
Laura G. Barrientos and Angela M. Gronenborn
Cyanovirin-N (CV-N), a cyanobacterial lectin, is a potent
viral entry inhibitor currently under development as a microbicide
against a broad spectrum of enveloped viruses. CV-N was originally
identified as a highly active anti-HIV agent and later, as
a virucidal agent against other unrelated enveloped viruses
such as Ebola, and possibly other viruses. CV-N’s antiviral
activity appears to involve unique recognition of Nlinked
high-mannose oligosaccharides, Man-8 and Man-9, on the viral
surface glycoproteins. Due to its distinct mode of action
and opportunities for harnessing the associated interaction
for therapeutic intervention, a substantial body of research
on CV-N has accumulated since its discovery in 1997. In this
review we focus in particular on structural studies on CV-N
and their relationship to biological activity.
[Back to top]
Inflammation in Atherosclerosis: New Opportunities for Drug
Discovery
Charles Q. Meng
Many lines of evidence indicate that inflammation is the
ultimate cause of atherosclerosis; high cholesterol levels
cause atherosclerosis through mechanism of inflammation. Drugs
designed to address inflammatory aspects of atherosclerosis
will likely be more effective than current therapies in treating
and preventing coronary artery disease.
[Back to top]
Peptide-Oligonucleotide Hybrids in Antisense Therapy
Tracie L. Pierce, Anthony R. White, Geoffrey
W. Tregear and Patrick M. Sexton
Antisense technology provides outstanding promise for treatment
of human disease, having broad applicability and high specificity.
Although advances have been made in antisense oligonucleotide
chemistry, leading to increased plasma and cellular stability,
and decreased toxicity, considerable potential remains for
the enhancement of oligonucleotide uptake for targeted delivery
of oligonucleotides. One promising avenue for achieving this
is via linkage of antisense oligonucleotides to peptide
carriers. This review looks at the current status of developments
in this area.
[Back to top]
Pharmacological Properties of Furoxans and Benzofuroxans:
Recent Developments
Hugo Cerecetto and Williams Porcal
The chemistry of furoxans (1, 2, 5-oxadiazole-2-oxides) and
benzofuroxans (benzo[1, 2-c]1, 2, 5-oxadiazole-1-oxides)
is very well known. These systems are widely used in organic
chemistry as intermediate compounds for the synthesis of numerous
heterocycles.
In the other hand, furoxan and benzofuroxan derivatives were
extensively studied as bioactive compounds. They possess remarkable
biological activities, such as anti-microbial and anti-parasitic
properties, mutagenic, immunosuppressive and anticancer effects,
anti-aggregating and vasorelaxant activity, among others.
In some cases, molecular mode of action was proposed.
Recently, the research and development in the medicinal chemistry
of these systems have produced hybrid compounds in which furoxan
or benzofuroxan moieties together with a classical drug moieties
are present in a single molecule. So, new anti-ulcer drugs,
calcium channel modulators and vasodilator derivatives were
described and they are currently in study.
In this presentation recent developments in the medicinal
chemistry of furoxans and benzofuroxans will be reviewed.
[Back to top]
Lactones: Generic Inhibitors of Enzymes?
Monika I. Konaklieva and Balbina J. Plotkin
The ability to affect eukaryotic and prokaryotic cellular
growth, signaling and differentiation is a continuing focus
in the pharmaceutical industry. The fundamental ability to
affect these cellular processes is inherent in lactones. Lactones,
which are ubiquitous in nature, reflect a broad phylogenetic
diversity indicative of their ability to act as simple alkylating
compounds, with their in situ activities falling
into one of two categories, i.e., protect or conquer. Medically,
their utility as pharmaceutical agents range from that of
antimicrobial to anti-neoplastic agent depending on the functional
groups attached.
[Back to top]
Involvement of Cannabinoids in Cellular Proliferation
Maria L. Lopez-Rodriguez, Alma Viso, Silvia Ortega-Gutierrez
and Ines Diaz-Laviada
The endogenous canabinoid system (ECS) is involved in the
regulation of an important number of central and peripheral
physiological effects. Among all these functions, the control
of the cellular proliferation has become a focus of major
attention as opening new therapeutic possibilities for the
use of cannabinoids as potential antitumor agents. The capacity
of endogenous and synthetic cannabinoids to induce apoptosis
of different tumoral cells in culture and in vivo,
the mechanism underlying and the potential therapeutic applications
are discussed in this review.
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