Mini-Reviews in Medicinal Chemistry, Volume 5, No. 5, 2005
Contents
Synthesis and Pharmacology of New
Camptothecin Drugs Pp.425-439
Russell
W. Driver and Li-Xi Yang
Structure and Biological Activity of
Heparinoid Pp.441-447
Neeraj
Kumar, A. Bentolila and A.J. Domb
Antitumour Quinones Pp.449-467
C.
Asche
Advancements in the Anti-Diabetes
Chemotherapeutics Based on Amino Acids, Peptides, and Peptidomimetics Pp.469-477
Rahul
Jain and Suresh Chawrai
Human Acetylcholinesterase Inhibitors:
Electronic-Topological and Neural Network Approaches to the Structure-Activity
Relationships Study Pp.479-487
F.
Kandemirli, M. Saracoglu and V. Kovalishyn
Recent Developments in Lipid Drugs Pp.489-498
J.
Raulin
The Chemotherapy of Chagas' Disease: An
Overview Pp.499-519
M.
Paulino, F. Iribarne, M. Dubin, S. Aguilera-Morales, O. Tapia and A.O.M.
Stoppani
Abstracts
[Back to top] Synthesis and Pharmacology of New
Camptothecin Drugs
Russell
W. Driver and Li-Xi Yang
Camptothecin (CPT)
drugs exhibit antineoplastic activity against colorectal, breast, lung and
ovarian cancers. This review briefly summarizes the pharmacology of CPT drugs,
examines four strategies and methods for the synthesis of camptothecins, and
finally discusses homocamptothecins and silatecans, two new classes of CPT
analog.
[Back to top] Structure and Biological Activity of
Heparinoid
Neeraj
Kumar, A. Bentolila and A.J. Domb
Heparin is a
biogenic anionic charged sulfated polysaccharide that has a range of desired
activities including inhibition of tumor metastasis and inhibition of
restenosis. However, its clinical use is limited totreating blood-clotting
disorders. Anionic macromolecules called heparinoids have been investigated
with the objective of developing heparin-like molecules with reduced
anti-coagulant activity and selective antimetastasis and anti-restenosis
activity. This mini-review summarizes the synthesis and biological activity of
the main synthetic heparinoids reported in the past three decades.
[Back to top] Antitumour Quinones
C.
Asche
Quinones still
comprise one of the largest classes of antitumour agents. For example, the
anthracycline antibiotics are among the most utilised anticancer agents ever
developed. Many other quinines were tested for their anticancer activity.
Though there are general and well-established mechanisms for quinone toxicity,
the exact contribution of the quinone moiety to the cytotoxic effect remains
frequently uncertain. However, DNA represents the main target for quinoid
antitumour agents and most of them belong to the groups of DNA intercalating
and/ or alkylating agents. But also other cellular structures such as heat
shock protein 90 or telomerase have been identified as targets for quinoid
compounds.
[Back to top] Advancements in the Anti-Diabetes Chemotherapeutics
Based on Amino Acids, Peptides, and Peptidomimetics
Rahul
Jain and Suresh Chawrai
Diabetes Mellitus
(DM) is a highly prevalent chronic disease. Recent years have witnessed
development of many new oral drugs; novel insulin analogs and their delivery
systems for the treatment of patients with either type-1 or type-2 DM. The
impetus for developing new antidiabetic drugs comes from the unmet need of
pharmacological tools that allow diabetic patients to achieve recommended
glucose control targets by precise, safe and effective ways. The number of
people afflicted with DM worldwide has increased considerably in recent years
and is projected to increase dramatically over the next decades. In the recent
times, design and synthesis of bioactive peptides and peptidomimetics has
undergone a paradigm shift. Nonproteinogenic amino acids, peptides and
peptidomimetics are emerging as novel drug candidates for the treatment of
various diseases and/or disorders. This review mainly discusses the advancements
in the usage of unnatural amino acids, peptides and peptidomimetics as
potential therapeutic agents for the treatment of DM.
[Back to top] Human Acetylcholinesterase Inhibitors:
Electronic-Topological and Neural Network Approaches to the Structure-Activity
Relationships Study
F.
Kandemirli, M. Saracoglu and V. Kovalishyn
The
Electronic-Topological (ETM) and Neural Network methods were applied to the
study of the "structure–acetylcholinesterase (AChE) inhibitor
activity" relationships for a series of physostigmine and
Nbenzylpiperidine derivatives. Molecular fragments specific for active
compounds and breaks of activity were calculated for human AChE by applying the
ETM and Neural Network methods. Requirements necessary for a compound to be
active were formulated; they are the result of detailed analysis of all
compounds under study. A comparative study of the activity features found for
human AChE was performed.
[Back to top] Recent Developments in Lipid Drugs
J.
Raulin
Lipopeptide lipid
moieties induce dendritic cell (DC) internalization and epitopes are recognized
by MHC, the major histocompatibility complex. HIV-1 (human immunodeficiency
virus type 1) lipopeptide vaccine candidate elicits immune responses, and
sustains HIV control after highly active antiretroviral therapy (HAART). Mp-
and Dp-MART (anti-melanoma lipopeptides) induce strong CTL (cytolytic T
lymphocyte) response. New BGTC, BGDA, TGKC lipoplexes mediate gene delivery,
e.g., into mouse pancreatic tumor nodules. Triterpene glycyrrhizic acid (GL)
inhibits SARS-CoV (severe acute respiratory syndrome associated coronavirus)
replication. Compared to CDV (cidofovir), CDV ether lipid esters have enhanced
activity against vaccinia (VV) and cowpox (CV) viruses in vitro. Oral
treatment of VV and CV infected mice with CDV ether lipid esters, as effective
as i.p. CDV, may be useful against orthopoxvirus infections in humans.
[Back to top] The Chemotherapy of Chagas' Disease: An Overview
M.
Paulino, F. Iribarne, M. Dubin, S. Aguilera-Morales, O. Tapia and A.O.M.
Stoppani
The review
presents: a) a brief description of the disease; b) a summary of the most
important metabolic targets so far identified in Trypanosome cruzi (T.
cruzi) along with corresponding inhibitor compounds; c) the current state
of knowledge on the trypanothione reductase system of trypanosomatids with
reference to oxidative stress defenses; d) detailed discussions on T. cruzi
trypanothione reductase inhibitors such as nitrofuranes, naphthoquinones and
phenothiazines. As yet, the chemotherapy of Chagas' disease remains an unsolved
problem. Further search for new drugs must continue by means of nucleating
existing chemotherapy efforts.