Mini-Reviews in Medicinal Chemistry, Volume 5, No. 4, 2005
Contents
Therapeutic Drugs for Targeting Chloroquine
Resistance in Malaria Pp.337-351
Vijay
Sharma
Folding and Mis-Folding of Peptides and
Proteins: Insights from Molecular Simulations Pp.353-359
Giacomo
M.S. De Mori, Massimiliano Meli, Luca Monticelli and Giorgio Colombo
Therapeutics and Prion Disease: Can
Immunisation or Drugs be Effective? Pp.361-366
J.
Sassoon, M. Sadowski, T. Wisniewski and D.R. Brown
Medicinal Chemistry and Properties of
1,2,4-Thiadiazoles Pp.367-379
Tim
Fat Tam, Regis Leung-Toung, Wanren Li, Michael Spino and Khashayar Karimian
Endothelin Receptor Antagonists: An Overview
of Their Synthesis and Structure-Activity Relationship Pp.381-408
Javed
Iqbal, Rashmi Sanghi and Saibal Kumar Das
Imidazole and Benzimidazole Derivatives as
Chemotherapeutic Agents Pp.409-424
Mariana
Boiani and Mercedes Gonzalez
Abstracts
[Back to top] Therapeutic Drugs for Targeting Chloroquine
Resistance in Malaria
Vijay
Sharma
While the
post-genomic era could lead into new targets for antimalarial drug development,
herein few successful targets including medicinals involved in those processes
are presented. Further, contribution of bioinorganic chemistry has also started
to make its impact in the field of pharmaceuticals. Therefore, metal chelators,
selected organometallics, and metalloantimalarials that would offer potential
therapeutic drugs are also discussed. Finally, a brief summary on
chloroquine-resistance mechanism(s) has been included.
[Back to top] Folding and Mis-Folding of Peptides and
Proteins: Insights from Molecular Simulations
Giacomo
M.S. De Mori, Massimiliano Meli, Luca Monticelli and Giorgio Colombo
In this paper, the
main achievements and problems of the application of all-atom molecular
simulations, with particular attention for Molecular Dynamics (MD), will be
critically reviewed. Starting from unfolding simulations, through biased
simulations, which require a knowledge of the native state conformation, to
folding studies based on the simple knowledge of the protein (or peptide)
sequence, the strengths and weaknesses of theoretical approaches to the study
of folding and their matching with experimental observations will be discussed.
Finally, we will give a critical outlook on the possible developments of this
field in the near future.
[Back to top] Therapeutics and Prion Disease: Can
Immunisation or Drugs be Effective?
J.
Sassoon, M. Sadowski, T. Wisniewski and D.R. Brown
Prion diseases are
of considerable importance because of the threat of a variant form of
Creutzfeldt Jakob disease that has emerged in recent years. Pre-clinical
diagnosis of prion diseases still remains poor and effective therapies also do
not exist at present. This review examines research on possible therapeutic strategies
that might have potential benefits if applied before neurodegeneration has
occurred.
[Back to top] Medicinal Chemistry and Properties of
1,2,4-Thiadiazoles
Tim
Fat Tam, Regis Leung-Toung, Wanren Li, Michael Spino and Khashayar Karimian
1,2,4-Thiadiazole
is a distinctive class of small heterocyclic thiol trapping agents that serve
as an interesting pharmacophore in the design of inhibitors targeting the
cysteine residues of proteins. X-Ray crystal structures of enzyme-inhibitor
complex indicate that the cysteine thiol reacts with the N-S bond of the
thiadiazole moiety to form a disulfide bond resulting in the inactivation of
the enzymes.
This review
addresses the medicinal chemistry and various properties of 1,2,4-thiadiazoles
in their potential as new electrophilic “warheads” for targeting the cysteine
residues of biomolecules (e.g, H+/K+ ATPase), and cysteine-dependent enzymes
(e.g., cathepsin B and transglutaminase).
[Back to top] Endothelin Receptor Antagonists: An Overview
of Their Synthesis and Structure-Activity Relationship
Javed
Iqbal, Rashmi Sanghi and Saibal Kumar Das
Endothelins (ETs)
are potent vasoconstrictor peptides and are associated with several disease
states like pulmonary hypertension, systemic hypertension and heart failure.
Endothelin-1 (ET-1) is the first member of the family and it has the receptor
subtypes known as ETA and ETB. The receptors ETA and ETB are attractive new
therapeutic targets for diseases associated with elevated ET-1 levels. Several
studies have thus led to the discovery of selective ETA receptor antagonists as
well as non-selective ETA/ETB antagonists. The preclinical and clinical studies
have clearly established that these antagonists are effective in the treatment
of essential hypertension, pulmonary hypertension, heart failure and
atherosclerosis. The advances in this area have resulted in the FDA approval of
the orally active dual antagonist Bosentan for pulmonary hypertension in 2001.
This review highlights the synthesis and structure-activity of the endothelin
receptor antagonists and covers the literature in this area up to 2001.
[Back to top] Imidazole and Benzimidazole Derivatives as
Chemotherapeutic Agents
Mariana
Boiani and Mercedes Gonzalez
Imidazole and
benzimidazole systems are presented in a large number of common therapeutics
agents. They were widely used in organic and medicinal chemistry, but recently
the development of N-oxide derivatives got an improvement from the point of
view of its chemical and biological activity.
Though we will
review recent developments in chemical and biological profiles (as antitumoral,
antiparasitic, antiviral and antimicrobial agents) of these heterocycle systems
and the corresponding N-oxides.