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Current
Bioactive Compounds
Current Bioactive Compounds
Volume 2, Number 1, March 2006
Contents
Editorial Pp. 1
Review Articles
The In Vitro and In Vivo Inhibitory Effect
of Dehydroaltenusin: A Specific Inhibitor of Mammalian DNA
Polymerase α
Pp. 3-11
Naoki Maeda, Shinji Kamisuki, Shunya Takahashi,
Hiromi Yoshida,Kengo Sakaguchi, Fumio Sugawara and Yoshiyuki
Mizushina
[Abstract]
Synthetic Ion Channels As Novel Antimicrobial Agents Pp.
13-18
Zachary T. Cusumano and George W. Gokel
[Abstract]
Use of PI Index in Computer-Aided Designing of Bioactive
Compounds Pp. 19-56
Padmakar V. Khadikar, Mircea V. Diudea, Jyoti
Singh, Peter E. John, Anjalee Shrivastva, Shalini Singh, Sneha
Karmarkar, Meenakshi Lakhwani and Purnima Thakur
[Abstract]
Effects of Eugenol on the Central Nervous System:
Its Possible Application to Treatment of Alzheimer’s
Disease, Depression, and Parkinson’s Disease Pp.
57-66
Yoshifumi Irie
[Abstract]
Bioactive Compounds
Anti-Cancer/Anti-Tumor Pp. 67
Anti-Diabetic Pp. 86
Anti-Viral Pp. 89
Anti-Inflammatory/Analgesic Pp. 96
Anti-Malarial Pp. 98
Anti-Microbial Pp. 99
Anti-Parasitic Pp. 104
Anti-Tuberculosis Pp. 105
Cardiovascular-Related Pp. 106
Central Nervous System-Related Pp. 108
Cholesterol-Lowering Pp. 113
Enzyme Inhibitors Pp. 114
Anti-Obesity Pp. 126
Abstracts
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Editorial
Conventional drug development, which likely to be remain
a dominant strategy in the near future, is based on the discovery
of potent molecular entities. Scientific literature is full
of the reports of discovery or development of interesting
molecular exciting against different therapeutic targets.
However, only a handful of these exciting discoveries are
seriously followed mainly due to lack of access to most readily
available and updated literature reports. The quarterly journal
Current Bioactive Compounds is an attempt to fill
this gap. We are glad that this journal has already received
attention of the fraternity scientists working in the field
of drug development and discovery.
This issue of Current Bioactive Compounds contains
brief descriptions and chemical structures of lead discoveries,
taken from the most authentic literature sources, and divided
into thirteen therapeutic categories. This will hopefully
enable readers to quickly spot the potential leads for further
exploration.
Keeping in view of the importance of in-depth analysis of
various classes of bioactive compounds against various diseases,
we have decided to include selected review articles in CBC
starting from this issue. The articles are contributed by
leading researchers in the field and focuses on various classes
of bioactive chemical compounds along with their mechanisms
of action and structure-activity relationships.
I hope this innovation in the format and scope of the Current
Bioactive Compounds will be welcomed by the readers and
will further enhance this impact of the publication.
At the end we acknowledge the editorial and secretarial staff
of the Bentham Science Publishers, for their help in bringing
this issue timely and neatly. Notable among them are the team
leader Mr. Mahmood Alam, and staff members, Dr. Ghulam Murtaza
Maharvi and Miss Samreen Laeeq.
ATTA-UR-RAHMAN
Ph.D. (Cantab.), D.Sc. (Cantab.)
M. IQBAL CHOUDHARY
Ph.D. (Kar.), D.Sc. (Kar.)
March 2006
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The In Vitro and In Vivo Inhibitory
Effect of Dehydroaltenusin: A Specific Inhibitor of Mammalian
DNA Polymerase α
Naoki Maeda, Shinji Kamisuki, Shunya Takahashi,
Hiromi Yoshida,Kengo Sakaguchi, Fumio Sugawara and Yoshiyuki
Mizushina
In the screening of the selective inhibitors of eukaryotic
DNA polymerases (pols), dehydroaltenusin was found to be an
inhibitor of pol α
from a fungus (Alternaria tennuis). This compound
inhibited only mammalian pol α,
and did not influence the activities of other replicative
pols such as pols δ
and ε,
but also showed no effect even on pol α
activity from another vertebrate, fish, or from a plant species.
Dehydroaltenusin also had no influence DNA metabolic enzymes
tested. The inhibitory effect of dehydroaltenusin on mammalian
pol α
was dose-dependent with IC50 value of 0.5 μM.
This effect was 10-fold stronger than that of aphidicolin,
a well-known potent eukaryotic pol α
inhibitor. The inhibitory mode of dehydroaltenusin for mammalian
pol α
activity was competitive with the DNA template-primer and
non-competitive with the dNTP substrate. We succeeded in chemically
synthesizing dehydroaltenusin, and the compound inhibited
the cell proliferation of human gastric cancer cell lines
by arresting the cells at the S-phase, and preventing the
incorporation of thymidine into the cells, indicating that
it blocks in vivo DNA replication by inhibiting pol
α.
This compound also induced cell apoptosis. Furthermore, we
investigated in vivo anti-tumor effects on nude mice
bearing solid tumors of the human cervical cancer cell line
HeLa. Dehydroaltenusin was significantly effective in suppressing
the growth of solid tumors, therefore, it was of interest
as a candidate drug for anti-cancer treatment. These results
suggested that dehydroaltenusin is a mammalian pol α-specific
inhibitor useful in both in vivo and in
vitro experiments.
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Synthetic Ion Channels As Novel Antimicrobial
Agents
Zachary T. Cusumano and George W. Gokel
Several families of novel synthetic ion channels have now
been developed. They exhibit many, but not all, of the properties
of protein ion channels. Some are peptides, but none is naturally
occurring. Their ability to insert in membranes and disrupt
ion homeostasis confers cellular toxicity upon them. Because
these compounds are both abiotic and cytotoxic to a range
of microbes, they have been investigated as antibiotics.
[Back to top]
Use of PI Index in Computer-Aided Designing of Bioactive
Compounds
Padmakar V. Khadikar, Mircea V. Diudea, Jyoti
Singh, Peter E. John, Anjalee Shrivastva, Shalini Singh, Sneha
Karmarkar, Meenakshi Lakhwani and Purnima Thakur
In this review we critically examine PI (Padmakar-Ivan) index
of organic compounds acting as drugs and discussed its applications
in Computer-Aided designing of bioactive compounds with special
reference to designing of carbonic anhydrase inhibitors, lipophilicity,
toxicity, tadpole narcosis, bio-concentration factor, diuretic
activity and carcinogenic activity of aromatic hydrocarbons
and heterocycles etc.
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Effects of Eugenol on the Central Nervous System:
Its Possible Application to Treatment of Alzheimer’s
Disease, Depression, and Parkinson’s Disease
Yoshifumi Irie
Eugenol (4-allyl-2-methoxyphenol) is a fragrant compound that
is commonly contained in various sorts of plants, especially
in spices and medicinal herbs. Eugenol has been used for dental
analgesic, which also has anti-convulsive and anti-microbial
activities. Besides, anti-inflammatory and antioxidative activities
of eugenol are known. A body of evidence suggests that eugenol
can be used as a drug for treatment of Alzheimer’s disease
(AD). According to recent reports, the extract of a medicinal
plant Rhizoma Acori Graminei (RAG) alleviates neurotoxicity
induced by amyloid beta peptides (Aβ)
in vitro and the active constituent of RAG is eugenol.
Eugenol inhibits Aβ-induced
excessive influx of calcium ion into neurons that causes neuronal
death. Moreover, eugenol possesses an antidepressant-like
activity. Eugenol, like other antidepressants, increases expression
of brain-derived neurotrophic factor (BDNF) gene in the hippocampus,
which is necessary for an antidepressant to exhibit its activity.
Furthermore, eugenol inhibits monoamine oxidase A (MAO-A)
and may restore monoamines that are decreased in the brain
of patients with depression. Thus, eugenol can be a good medicine
for AD and depression. Here we suggest that eugenol and its
analogs can be used also for other diseases of the central
nervous system (CNS) including Parkinson’s disease (PD).
This article reviews the previous investigations concerning
effects of eugenol including its analogs on the CNS and describes
perspectives of this highly potential compound.
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