| Recent
Patents on Anti-Infective Drug Discovery
ISSN: 1574-891X
Recent Patents on Anti-Infective
Drug Discovery
Volume 3, Number 2, June 2008
Contents
NS5A - From Obscurity to New Target for HCV Therapy
Pp. 77-92
Uli Schmitz and Seng-Lai Tan
[Abstract]
Strategies for Effective Naked-DNA Vaccination
Against Infectious Diseases Pp. 93-101
Pieranna Chiarella, Emanuela Massi, Mariangela
De Robertis, Vito M. Fazio and Emanuela Signori
[Abstract]
Preclinical Animal Models for Discovery of New TB
Drugs and Drug Combinations Pp. 102-116
Boris V. Nikonenko, Katherine A. Sacksteder, Sam Hundert,
Leo Einck and Carol A. Nacy
[Abstract]
Tigecycline: A New Treatment Choice Against
Acinetobacter baumannii Pp. 117-122
Virginia Bosó-Ribelles, Eva Romá-Sánchez,
Jorge Carmena, Cristina Cáceres and Daniel
Bautista
[Abstract]
A Review of the Carbapenems in Clinical Use and
Clinical Trials Pp. 123-131
Tze S. Lo, Justin M. Welch, Augusto M. Alonto, and
Eileen A.R. Vicaldo-Alonto
[Abstract]
Pharmacogenomics of Antiretrovirals Pp.
132-135
Bernardino Roca
[Abstract]
Recent Patents on Melanoma with Focus on Genetic Strategies
Pp. 136-144
Talia Gramoccia, Rosita Saraceno, Alessandro
D. Stefani and Sergio Chimenti
[Abstract]
Cefepime and its Role in Pediatric Infections
Pp. 145-148
Sukhbir Kaur Shahid
[Abstract]
Evaluation of the Anthelminthic Activity of Garlic
(Allium sativum) in Mice Naturally Infected with
Aspiculuris tetraptera Pp. 149-152
Erol Ayaz, Idris Türel, Abdurrahman
Gül and Orhan Yilmaz
[Abstract]
Patent Selections Pp. 153-156
Abstracts
[Back to top]
NS5A - From Obscurity to New Target for
HCV Therapy
Uli Schmitz and Seng-Lai Tan
The hepatitis C virus (HCV) non-structural 5A (NS5A)
protein is essential for viral RNA replication and may play
a role in subverting host intracellular signaling pathways.
Although no intrinsic enzymatic activity has been ascribed
to NS5A, this proline-rich hydrophilic phosphoprotein is likely
to exert its functions by interacting with viral and cellular
factors. Recent studies using the HCV replicon cell culture
system as a model for HCV RNA replication as well as for high-throughput
screening of pharmacological inhibitors have revealed blockade
of NS5A as a promising therapeutic strategy for the treatment
of HCV. This review will summarize our progress in understanding
the role of NS5A in HCV RNA replication and will introduce
the most recent patents on inhibitors of NS5A.
[Back to top]
Strategies for Effective Naked-DNA Vaccination Against
Infectious Diseases
Pieranna Chiarella, Emanuela Massi, Mariangela
De Robertis, Vito M. Fazio and Emanuela Signori
To date, vaccination is an active area of investigation
for its application to a great variety of human diseases including
infections and cancer. In particular, naked-DNA vaccination
has arisen as effective strategy in the preventive medicine
field with promising future prospects. The ability of plasmid
DNA to activate the humoural and the cellular arms of the
immune system against the encoded antigen have resulted in
intensive study of new strategies aimed at increasing the
DNA vaccine immunogenicity. Nevertheless, plasmid-based vaccines
emerged as a safer and advantageous alternative with respect
to viral vector vaccines. Recent advances in both the immunological
and biotechnological research field made it possible to enhance
significantly the DNA vaccine potency. Most of these approaches
are based on both the discovery of novel delivery systems
and the implementation of plasmid constructs, achieved through
genetic engineering. In this review, we will describe some
of the most relevant patents issued in the last ten years,
supporting the progress made in naked-DNA vaccination against
infectious diseases.
[Back to top]
Preclinical Animal Models for Discovery of New TB
Drugs and Drug Combinations
Boris V. Nikonenko, Katherine A. Sacksteder, Sam Hundert,
Leo Einck and Carol A. Nacy
Tuberculosis (TB) remains one of the leading infectious
killers in the world. New anti-TB drugs and more effective
drug combinations are urgently needed, particularly given
the increasing incidence of drug-resistant TB and HIV-TB co-infection.
This review describes the available mouse models of TB and
describes their utility in the evaluation of new TB drug candidates
and in the evaluation of the efficacy of new TB drug combinations.
Some of the most recent patents on promising TB drug-candidates
are also mentioned here.
[Back to top]
Tigecycline: A New Treatment Choice Against Acinetobacter
baumannii
Virginia Bosó-Ribelles, Eva Romá-Sánchez,
Jorge Carmena, Cristina Cáceres and Daniel
Bautista
Acinetobacter baumannii (AB) is a gram-negative organism
that has emerged recently as a major cause of nosocomial infections,
because of the extent of its antimicrobial resistance and
its persistence in the hospital environment, where intensive
care units are the place of greatest risk for acquiring AB.
There is no treatment of choice for AB and it’s treatment
is based on clinical experience and in vitro susceptibility
testing. Also, nowadays Acinetobacter resistance
to carbapenems is common and isolates resistant to colistin
and polymyxin B have been reported.
Tigecycline, the 9-tert-butyl-glycylamido derivative of minocycline,
exhibits a broad-spectrum of activity against numerous pathogens,
including AB and several reports place it among the antimicrobials
with lower MIC for AB. Tigecycline overcomes the two major
mechanisms of resistance to tetracyclines (ribosomal protection
and efflux), but tigecycline resistance emerging during therapy
has been reported.
Tigecycline efficacy has been demonstrated in clinical studies
in skin and skin structure infections and in complicated intra-abdominal
infections but, although it seems a good alternative for the
treatment of AB infections, there is few evidence about its
use in these cases and more clinical experience and adequate
trials are needed. The present review shows the recent patents
related to treatment by tigecycline in different AB infections.
[Back to top]
A Review of the Carbapenems in Clinical Use and Clinical
Trials
Tze S. Lo, Justin M. Welch, Augusto M. Alonto, and
Eileen A.R. Vicaldo-Alonto
Despite alarming data showing the ever increasing number of
bacteria becoming resistant to different classes of antibiotics
through various mechanisms, the carbapenems remain a unique
class of antibiotics that possess the broadest spectrum against
Gram-positive, Gram-negative, aerobic and anaerobic organisms.
However, bacteria, such as methicillinresistant Staphylococcus
aureus (MRSA) and Pseudomonas aeruginosa, carry
mechanisms that can inactivate the carbapenems. This article
gives a review of the carbapenems that are currently in clinical
use as well as discusses the new carbapenems that are in clinical
trials. These new carbapenems show promising potential to
overcome the resistance against the presently existing carbapenems.
The present article shows the recent patents using carbapenems
as an effective antibiotic.
[Back to top]
Pharmacogenomics of Antiretrovirals
Bernardino Roca
HIV infection is a serious but treatable disease, yet
current treatment is limited by development of resistance
and high rates of adverse drug reactions.
Antiretroviral therapy is especially suitable for pharmacogenomic
investigation as both drug exposure and treatment response
can be reliably measured. Increasing knowledge about genes
implicated in pharmacokinetics, mode of action, efficacy,
and toxicity of drugs has already provided relevant results
for clinical practice, for example:
• The strong association of the abacavir hypersensitivity
reaction with HLA-B*5701 permits testing patients
for the allele, and if present avoiding the drug and therefore
preventing the reaction.
• Persons with the allele CYP2B6*6 present higher efavirenz
“area under the curve” and have increased risk
of neuropsychological toxicity.
Additional gene variants are being discovered that influence
the action of antiretroviral drugs. And, moreover, it is expected
that larger-scale comprehensive genome approaches will profoundly
improve the landscape of knowledge of HIV therapy in the future.
The present article shows some recent patents related to the
treatment of viral infections.
[Back to top]
Recent Patents on Melanoma with Focus on Genetic Strategies
Talia Gramoccia, Rosita Saraceno, Alessandro
D. Stefani and Sergio Chimenti
Recent advances in molecular biology have enhanced the
understanding of the pathology of melanocytic lesions. Several
targetable pathways, responsible for survival and apoptosis
resistance in melanoma cells, have been described and current
research has focused on mechanism inactivating these pathways.
However, the therapeutic resistance of malignant melanoma
remains the main limit that cast the poor prognosis of cutaneous
melanoma. Current advances in high-resolution genome-wide
technologies, as well as gene-specific mutational analysis,
in conjunction with genetic and phenotypic analyses, improved
animal models, may ultimately help to better define the seminal
molecular events contributing to disease pathogenesis and
ultimately identify more effective therapeutic targets. The
focus of this review is to summarize the emerging patents
in the treatment and diagnosis of melanoma related to the
latest genetic models and bio-molecular discoveries.
[Back to top]
Cefepime and its Role in Pediatric Infections
Sukhbir Kaur Shahid
Cefepime is a semi-synthetic fourth generation cephalosporin
with broader Gram-positive and excellent Gram-negative bacterial
coverage. Its extended anti-microbial activity and infrequent
tendency to develop resistance makes it popular for treatment
of infections due to multi-drug resistant organisms. It has
good efficacy against β-lactamase
and ESBL (extended spectrum β-lacatamase)-secreting
pathogens, and it has shown great promise in management of
children with severe and nosocomial infections. It possesses
superior bactericidal action compared to other cephalosporins
and is a cheaper and safe alternative to the carbapenems.
It is well-tolerated but needs dose adjustments in newborns,
and in children with renal insufficiency. Cefepime is a valuable
antibiotic but it should be used judiciously as unnecessary,
improper and prolonged use may lead to emergence of cefepime-insensitive
bacteria and risk of drop in the efficacy of cefepime. Various
recent patents of cefepime have been launched which deal with
improvements in its preparation, and with its combinations
with β-lactamase
inhibitors and newer antibiotics such as linezolid. These
developments may further augment the usefulness of cefepime
in pediatric infections.
[Back to top]
Evaluation of the Anthelminthic Activity of Garlic
(Allium sativum) in Mice Naturally Infected with
Aspiculuris tetraptera
Erol Ayaz, Idris Türel, Abdurrahman
Gül and Orhan Yilmaz
This study was performed to investigate the anthelmentic (nematodes)
effect of garlic in Swiss albino mice naturally infected with
Aspiculuris tetraptera. Natural infection was determined
by the use of cellophane tape method on the perianal region
and by the technique of centrifugal flotation of stool samples.
The infected mice were divided into three groups; namely,
Group 1: garlic treatment groups (n: 18), Group 2: positive
control (treated with ivermectin, n: 19) and Group 3: untreated
control group (n: 19). The mice in Group 1 were given orally
freshly crushed garlic homogenates every day for 7 days. The
animals in Group 2 were treated with ivermectin intramuscular
at a dose of 0.2 mg/kg body weight. The mice in Group 3 received
only serum physiologic orally. After 8 days of administrations,
all mice were killed humanely using inhalation anaesthesia
and then the parasites in the intestine were counted. It was
observed that garlic and ivermectin were 91.24 % and 78.03
% effective against A. tetraptera in naturally infected
mice, respectively. Results obtained from this study were
compared statistically and differences were found to be significant
(p<0.001). It was found that garlic was efficient along
the duration of the treatment in mice. Garlic may be useful
as an alternative treatment against nematode parasites in
animals and human. This article includes a new research using
Allium sativum anthelmentic effect on mouse and has
been patented.
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