Archive for the ‘News’ Category

New hepatitis C drug

Scientists in the UK have developed a compound to combat the hepatitis C virus that could be taken as a pill.

David Pryde and his team from Pfizer Global Research and Development, Sandwich, have made new compounds to activate a protein in the immune system called TLR7 – toll-like receptor 7 – which fights the infection. Toll-like receptors identify foreign DNA, such as a virus, and produce proteins that inhibit the virus’ replication.

300 million people suffer from hepatitis C worldwide. The virus that causes the disease resides in the liver and can lead to cirrhosis, with some sufferers requiring liver transplants. Current treatments only cure half of patients and are administered intravenously. Recent research has focused on increasing the effectiveness of the drugs and on developing oral treatments.

Pryde’s team made heterocyclic analogues based on the structure of purines, known activators of TLR7 and the basis of current oral drugs. ‘The most potent TLR7 agonists are purine-based,’ explains Pryde. ‘But we wanted to design potent non-purine based agonists to maximise the chances of avoiding any unwanted off-target pharmacology.’ 


The compounds activate a protein in the immune system, which fights hepatitis 

Read the full story in Chemistry World

The discovery of a novel prototype small molecule TLR7 agonist for the treatment of hepatitis C virus infection
David C. Pryde, Thien-Duc Tran, Peter Jones, Gemma C. Parsons, Gerwyn Bish, Fiona M. Adam, Mya C. Smith, Donald S. Middleton, Nick N. Smith, Frederick Calo, Duncan Hay, Michael Paradowski, Katie J. W. Proctor, Tanya Parkinson, Carl Laxton, David N. A. Fox, Nigel J. Horscroft, Giuseppe Ciaramella, Hannah M. Jones, Jonathan Duckworth, Neil Benson, Anthony Harrison and Rob Webster.
Med. Chem. Commun., 2011, DOI: 10.1039/c0md00197j
Link to journal article

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)

MedChemComm Issue 2 published on line- Free access!

Our second issue of MedChemComm 2011 is here already!

This new and exciting issue comes with two reviews.
The first one by Paul Leeson and collegues on the impact of ion class and the time on the properties of oral drugs and the second one by Peter Kovacic and Ratnasamy Somanathan on the mechanisms of aromatic primary amines and the influence on the physiological activity.

The issue also contains six vibrant concise articles that bring you the best medicinal chemistry research.
From 2D and 3D activity landscape representations to imaging contrast agents. For those of you who are more synthetic medchems you can find articles on the synthesis and biological activities of AA-Trp-Trp-OBzl and isoquinolones. We close the issue with a study of activation energies and their influence in the stability of drugs and a final article on HIV-integrase inhibitors.

What do you think? We would like to receive your feedback on the new RSC medicinal chemistry journal MedChemComm!

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)

New antibiotics repair faulty genes

Many genetic diseases, such as cystic fibrosis and muscular dystrophy, are caused by DNA mutations that terminate protein synthesis in the mutant gene. Aminoglycoside based antibiotics have been shown to stop these mutations but are often toxic and cause unpleasant side-effects in patients.   

Now Timor Baasov and colleagues have designed and synthesised new aminoglycoside derivatives that show enhanced targeting and reduced cell toxicity, compared with the leading antibiotic gentamicin. Baasov’s compounds contain a chiral methyl group at the side-chain of the ribosamine ring, which they claim could be an essential feature responsible for the compound’s biological activity.

These findings could have immediate therapeutic applications for the treatment of many genetic diseases and could also aid treatment of several types of cancer caused by DNA mutations.

Download this paper for free now!

Repairing faulty genes by aminoglycosides: Identification of new pharacophore with enhanced suppression of disease-causing nonsense mutations.  
Jeyakumar Kandasamy, Dana Atia-Gilkin, Valery Belakhov and Timor Baasov 
Med.Chem. Commun, 2011, Advance Article, DOI: 10.1039/C0md00195c

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)

MedChemComm Issue 1 2011 is now published!

Welcome to MedChemComm Issue 1 of the New Year!

 

2011 is going to be a very exciting year for MedChemComm and you will still be able to read all our content for free until the end of the year. You just need to register for a RSC personal account.
We also encourage you to keep up-to-date with the latest news by following us on Twitter, signing up for our e-alerts and receiving MedChemComments (our newsletter) in your inbox.

Don’t forget to keep an eye on the MedChemComm Blog! You can also sign up for our RSS feed.

Without further delay, here you have the first issue of 2011.

We start the year with a great selection of articles, including ‘Proteochemometric Modeling as a Tool to Design Selective Compounds and Extrapolating to Novel Targets’ by Andreas Bender et al. and ‘Evaluation of FR901464 analogues in vitro and in vivo’ by Kazunori Koide et al.

I hope you find the articles interesting and you consider submitting your research to MedChemComm in the near future.

From the MedChemComm editorial office we wanted to wish a very happy New Year to all our readers, authors and referees and a very successful one in medicinal chemistry.

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)

MedChemComm is now indexed in ISI

We are really pleased to say that MedChemComm is now being indexed in ISI Web of Science.

Issue 1 is already there and some of the articles have already been cited. Congratulations to Jean-Louis Reymond, Julia M. Adam, Franco Chimenti and Zhisong Lu and their research teams for being the first cited authors of MedChemComm in ISI.

Remember that you can now read all these articles for free!

Happy Holidays and best wishes for 2011!

Chemical space as a source for new drugs
Jean-Louis Reymond, Ruud van Deursen, Lorenz C. Blum and Lars Ruddigkeit
Med. Chem. Commun., 2010, 1, 30-38
DOI: 10.1039/C0MD00020E

Design, synthesis, and structure–activity relationships of indole-3-carboxamides as novel water soluble cannabinoid CB1 receptor agonists
Julia M. Adam, Jim Cairns, Wilson Caulfield, Phillip Cowley, Iain Cumming, Morag Easson, Darren Edwards, Morag Ferguson, Richard Goodwin, Fiona Jeremiah, Takao Kiyoi, Ashvin Mistry, Elizabeth Moir, Richard Morphy, Jason Tierney, Mark York, James Baker, Jean E. Cottney, Andrea K. Houghton, Paul J. Westwood and Glenn Walker
Med. Chem. Commun., 2010, 1, 54-60
DOI: 10.1039/C0MD00022A

Synthesis and selective inhibition of human monoamine oxidasesof a large scaffold of (4,5-substituted-thiazol-2-yl)hydrazones
Franco Chimenti, Daniela Secci, Adriana Bolasco, Paola Chimenti, Arianna Granese, Simone Carradori, Melissa D’Ascenzio, Matilde Yáñez and Francisco Orallo
Med. Chem. Commun., 2010, 1, 61-72
DOI: 10.1039/C0MD00014K

Effect of particle shape on phagocytosisof CdTe quantum dot–cystinecomposites
Zhisong Lu, Yan Qiao, Xin Ting Zheng, Mary B. Chan-Park and Chang Ming Li
Med. Chem. Commun., 2010, 1, 84-86
DOI: 10.1039/C0MD00008F

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)

MedChemComm in ISI

This week the MedChemComm team received the news that the journal has been accepted into ISI products by Thomson Reuters. In the next month you will be able to see MedChemComm listed in the following product:

* Science Citation Index Expanded
* Chemistry Citation Index
* Biological Abstracts
* BIOSIS Previews

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)

Analysis of public datasets of antimalarial “hits” and drugs

Sean Ekins and Tony Williams examine molecular properties across datasets of antimalarial screening hit compounds and compare them with compounds screened against Mycobacterim tuberculosis to identify patterns, trends or relationships.

The antimalarial hits were also filtered with computational rules to identify potentially undesirable substructures. They were surprised that approximately 75–85% of these compounds failed one of the sets of filters that they applied during this work.

To find out more about their findings I invite you to read this article. If you have something to say,  you can comment on this blog.

Meta-analysis of molecular property patterns and filtering of public datasets of antimalarial “hits” and drugs
Sean Ekins and Antony J. Williams
Med. Chem. Commun., 2010, Advance Article
DOI: 10.1039/C0MD00129E, Concise Article

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)

Novel approach to high-throughput screening of molecules

Jason Kettle and colleagues at AstraZeneca in UK outline a simple and direct strategy for extraction of potentially high value reagents from patent and other medicinal literature.

This approach is based on fragmentation and analysis of molecules described in patent and medicinal chemistry literature. They also highlight an example of key secondary amines with potential for broad applicability across medicinal chemistry.

Read it free to access.

Data-mining patent literature for novel chemical reagents for use in medicinal chemistry design
Jason G. Kettle, Richard A. Ward and Ed Griffen
Med. Chem. Commun., 2010, Advance Article
DOI: 10.1039/C0MD00148A, Concise Article

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)

Tumour detection takes an ultrasonic leap

By Philippa Ross

Hollow silica nanoparticles filled with gas behave as efficient contrast agents for use in ultrasound imaging. This could improve detection of tumours in breast cancer patients, claim US scientists.

Ultrasound imaging is a safe, fast and non-invasive technique used for medical diagnosis. However, one shortcoming is the inferior image contrast compared to more sophisticated magnetic resonance imaging (MRI). To improve this, radiologists use microbubble contrast agents to enhance the reflection of ultrasonic waves and therefore improve the quality of the ultrasound image, or radioactive seeds that are injected into the patient before surgery to visualise the entire tumour.
However, the contrast particles – normally comprised of a soft protein outer shell and a gas core – can be unstable due to their high sensitivity to changes in pressure, while the radioactive seeds have to be painfully injected into the patient and only last a few hours.

Now, a team led by William Trogler at the Univeristy of Califonia, San Diego have developed a stable, hard shell, hollow particle which, when filled with gas, produces a ultrasound signal and can be safely and painlessly injected into breast tissue to locate tumours. The gas-filled microbubbles adhere to human breast tissue for days and have a longer imaging lifetime than their soft counterparts, explains Trogler. So if used in early stage breast cancer patients, they could help surgeons better visualise the tumours and remove it all in one procedure.

Elizabeth Shaughnessy, a specialist in breast diseases at the University of Cincinnati in the US agrees. ‘The injection of these silica hollow spheres with gas-filled contrast provides a less toxic alternative, [to radioactive seeds] that won’t degrade within a short time period.’ She adds that the work is ‘highly innovative and will have great appeal to surgeons, radiologists and patients, as well as operating staff.

It is still early days but next Trogler and his team hope to move to animal models, toxicology studies and eventually clinical trials. Methods are also being developed to make biodegradable gas filled silica micro and nanoshells that would broaden the possible imaging applications.

This story has been published on the  Highlights in Chemical Biology website.

Read the paper free to access

Hard shell gas-filled contrast enhancement particles for colour Doppler ultrasound imaging of tumors
H. Paul Martinez, Yuko Kono, Sarah L. Blair, Sergio Sandoval, Jessica Wang-Rodriguez, Robert F. Mattrey, Andrew C. Kummel and William C. Trogler, Med. Chem. Commun., 2010, 1, 266
DOI: 10.1039/c0md00139b

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)

MedChemComm article by William Troger picked up in media outlets

The concise article by Robert F. Mattrey, Andrew C. Kummel, William Troger and colleagues at University of California, San Diego, on gas filled hollow porous silica microshells for ultrasound image contrast has had a tremendous impact in media outlets worldwide. This article is now included in MedChemComm Issue 4 and as all the MedChemComm content, it is free to access.

These are some of the web pages in which the article has been highlighted:

Congratulations to the authors! It is a truly interesting piece of research.

You can read it for free here:

Hard shell gas-filled contrast enhancement particles for colour Doppler ultrasound imaging of tumors
H. Paul Martinez, Yuko Kono, Sarah L. Blair, Sergio Sandoval, Jessica Wang-Rodriguez, Robert F. Mattrey, Andrew C. Kummel and William C. Trogler
Med. Chem. Commun., 2010, 1, 266-270
DOI: 10.1039/C0MD00139B , Concise Article

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)