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Mini-Reviews
in Medicinal Chemistry
ISSN: 1389-5575
Mini-Reviews in Medicinal
Chemistry
Volume 7, Number 12, December 2007
Contents
Combretastatin A-4 Analogs as Anticancer Agents
pp. 1186-1205
Anurag Chaudhary, S.N. Pandeya, P. Kumar, P.P. Sharma, S.
Gupta, N. Soni, K.K. Verma and G. Bhardwaj
[Abstract]
Chemistry and Biology of Heparin Mimetics that Bind
to Fibroblast Growth Factors Pp. 1206-1235
Hammed H.A.M. Hassan
[Abstract]
Two-Peptide Lantibiotics: A Medical Perspective
Pp. 1236-1247
Elaine M. Lawton, R. Paul Ross, Colin Hill and Paul D.
Cotter
[Abstract]
Tetraspanins-Structural and Signalling Scaffolds that
Regulate Platelet Function Pp. 1248-1254
Matt W. Goschnick and Denise E. Jackson
[Abstract]
Synthetic Approaches to the 2006 New Drugs Pp.
1255-1269
Kevin K.-C. Liu, Subas M. Sakya and Jin Li
[Abstract]
Glycodendrimers as Anti-Adhesion Drugs Against Type
1 Fimbriated E. coli Uropathogenic Infections Pp.
1270-1283
Mohamed Touaibia and René Roy
[Abstract]
Abstracts
[Back to top]
Combretastatin A-4 Analogs as Anticancer Agents
Anurag Chaudhary, S.N. Pandeya, P. Kumar, P.P. Sharma, S.
Gupta, N. Soni, K.K. Verma and G. Bhardwaj
Combretastatin A-4 (CA-4) is one of the most potent antimitotic
and antiangiogenic agents of natural origin. It has displayed
potent antitumor effect in a wide variety of preclinical tumor
models. Till date various CA-4 analogs have been synthesized
and evaluated for anticancer activity. This review is an attempt
to compile the medicinal chemistry of various synthesized
CA-4 analogs.
[Back to top]
Chemistry and Biology of Heparin Mimetics that Bind to Fibroblast
Growth Factors
Hammed H.A.M. Hassan
We aim from this review to stimulate further research
in this area by providing a description of the different types
of inhibitors containing heparin mimetic molecules that have
recently been reported and data on their biological activity.
Molecules that mimic heparin and bind to heparin-binding growth
factors are important building blocks for synthetic biomaterials.
Different types of synthetic mimics of the biological properties
of heparin have been prepared including high molecular weight
compounds or small molecule mimics. Peptide-based mimics of
heparin functionality are limited and because of their low
degree of sulfation, they are natural targets as heparin mimics.
Aromatic sulfonamide derivatives exhibit a range of bioactivities
and a novel angiogenesis inhibitor (E 7820) is used as a TF
model for screening assay. The anticoagulant activity of the
known heparin pentasaccharide sequence prompted synthetic
efforts aimed at the procurement of this structure as well
as a host of related sequences. Chemical modification of the
natural or synthetic heparin increased factor activation of
AT III Xa affinity. A variety of non-peptide non-saccharides
inhibitors as anti-angiogenesis therapies directed against
the VEGFR kinase are a promising and well-validated therapeutic
approach under active evaluation of their safety and efficacy
in multiple clinical trials. These low molecular weight modulators
could be useful tools for biologists and may have potential
as drugs or as leads for drug development.
[Back to top]
Two-Peptide Lantibiotics: A Medical Perspective
Elaine M. Lawton, R. Paul Ross, Colin Hill and Paul D.
Cotter
Lantibiotics are ribosomally synthesised, post-translationally
modified antimicrobial peptides that exhibit activity against
a wide-range of Gram positive bacteria. During the last decade
a number of two-peptide lantibiotics, i.e. lantibiotics that
function optimally as a consequence of the synergistic activity
of two peptides, have been identified, six of which (lacticin
3147, staphylococcin C55, plantaricin W, Smb, BHT-A and haloduracin)
are closely related. It has been established in at least one
instance, i.e. lacticin 3147, that these are extremely potent
antimicrobials, which are active at nanomolar concentrations
against a number of microorganisms, exhibit activity against
multidrug resistant nosocomial pathogens such as MRSA and
VRE and significantly, to date the development of significant
levels of resistance has not been apparent. Given the similarity
between lacticin 3147 and related two-peptide lantibiotics,
it is likely that they too possess similarly beneficial traits
and thus could potentially have medical and veterinary applications.
In addition to discussing these aspects of two-peptide lantibiotic
reasearch, this review will focus on new developments in this
area pertaining to studies elucidating the mechanism of action
of these antimicrobials, the use of bioengineering to reveal
the location of essential and variable domains therein and
the potential for the use of in vivo and in vitro
engineering to create derivatives with even greater activities
against specific target organisms.
[Back to top]
Tetraspanins-Structural and Signalling Scaffolds that Regulate
Platelet Function
Matt W. Goschnick and Denise E. Jackson
There are several tetraspanins present in platelets including
CD9, CD151, TSSC6, and CD63. Recent studies in knockout mouse
models have revealed that CD151 and TSSC6 are physically and
functionally involved in regulation of the ‘outside-in’
signalling properties of the major platelet integrin,integrin
αiib
β3 and thrombus
stability in vivo.
[Back to top]
Synthetic Approaches to the 2006 New Drugs
Kevin K.-C. Liu, Subas M. Sakya and Jin Li
New drugs are introduced to the market every year and each
individual drug represents a privileged structure for its
biological target. In addition, these new chemical entities
(NCEs) not only provide insights into molecular recognition,
but also serve as drug-like leads for designing future new
drugs. To these ends, this review covers the syntheses of
16 NCEs marketed in 2006.
[Back to top]
Glycodendrimers as Anti-Adhesion Drugs Against Type
1 Fimbriated E. coli Uropathogenic Infections
Mohamed Touaibia and René Roy
Bacterial drug resistance against antimicrobial agents
is a prevalent and central worldwide impasse. Infections with
resistant organisms lead to adverse clinical outcomes, increased
mortality, and are costly to healthcare systems. Several infectious
diseases are initiated by the binding of pathogenic lectins
to host cells glycoconjugates. The molecular understanding
of these adhesion phenomena is crucial and presents promising
new alternatives compared to traditional antibiotic therapies.
Glycans or glycan mimetics could be used to inhibit the initial
recognition events leading to adhesion and colonization of
host tissues by pathogens. The bladder and urothelial lining
are widely covered by cell surface glycoproteins bearing the
required carbohydrate ligands responsible for the adhesion
phenomena. However, when these interactions are measured on
a per saccharide basis, they are generally too weak (mM) for
the design of beneficial inhibition therapies. The interactions
between microbial pathogens and host cells are often governed
by polyvalent and overall strong avidities. To overcome this
drawback, glycobiologists have design a new family of well-defined
small macromolecules, called glycodendrimers that can successfully
address this issue. This review will provide a brief introduction
on glycodendrimers and detailed descriptions of design and
applications of mannosylated inhibitors against fimbriated
type 1 E. coli.
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