BSP :: Mini-Reviews in Medicinal Chemistry Home Page

Contents

Recent Progress in Structure Activity Relationship and Mechanistic Studies of Taxol Analogues Pp.1-12
W.-S. Fang and X.-T. Liang
[Abstract] [Full text article]

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] [Full text article]

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] [Full text article]

Inflammation in Atherosclerosis: New Opportunities for Drug Discovery Pp.33-40
Charles Q. Meng
[Abstract] [Full text article]

Peptide-Oligonucleotide Hybrids in Antisense Therapy Pp.41-55
Tracie L. Pierce, Anthony R. White, Geoffrey W. Tregear and Patrick M. Sexton
[Abstract] [Full text article]

Pharmacological Properties of Furoxans and Benzofuroxans: Recent Developments Pp.57-71
Hugo Cerecetto and Williams Porcal
[Abstract] [Full text article]

Lactones: Generic Inhibitors of Enzymes? Pp.73-95
Monika I. Konaklieva and Balbina J. Plotkin
[Abstract] [Full text article]

Involvement of Cannabinoids in Cellular Proliferation Pp.97-106
Maria L. Lopez-Rodriguez, Alma Viso, Silvia Ortega-Gutierrez and Ines Diaz-Laviada
[Abstract] [Full text article]

Abstracts

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Recent Progress in Structure Activity Relationship and Mechanistic Studies of Taxol Analogues
W.-S. Fang and X.-T. Liang
[Full text article]

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.

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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
[Full text article]

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.

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The Highly Specific Carbohydrate-Binding Protein Cyanovirin-N: Structure, Anti-HIV/Ebola Activity and Possibilities for Therapy
Laura G. Barrientos and Angela M. Gronenborn
[Full text article]

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.

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Inflammation in Atherosclerosis: New Opportunities for Drug Discovery
Charles Q. Meng
[Full text article]

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.

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Peptide-Oligonucleotide Hybrids in Antisense Therapy
Tracie L. Pierce, Anthony R. White, Geoffrey W. Tregear and Patrick M. Sexton
[Full text article]

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.

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Pharmacological Properties of Furoxans and Benzofuroxans: Recent Developments
Hugo Cerecetto and Williams Porcal
[Full text article]

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.

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Lactones: Generic Inhibitors of Enzymes?
Monika I. Konaklieva and Balbina J. Plotkin
[Full text article]

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.

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Involvement of Cannabinoids in Cellular Proliferation
Maria L. Lopez-Rodriguez, Alma Viso, Silvia Ortega-Gutierrez and Ines Diaz-Laviada
[Full text article]

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.