Archive for January, 2012

Themed issue on epigenetics just published

The web-based issue in MedChemComm termed “Epigenetics” is a timely collection of articles covering recent developments in epigenetic medicinal chemistry research in the broadest sense, including reviews of the field, original articles, and perspectives looking in to the future.

Epigenetics is the study of changes in phenotype or gene expression that cannot be related to a change in gene sequence. From being seen as a fringe science looking at strange phenomena, it is today very clear that epigenetic mechanisms are crucial for cell development and a cause of many diseases. In particular, many cancers have been shown to have an epigenetic component, and cancer research provided epigenetic compounds before the proteins involved were known, as exemplified by Breslow’s pioneering work on hydroxamic acids. Today several histone deacetylase (HDAC) inhibitors have reached the market, and this area is the most established part of the research field. Similarly, many other enzymes involved in epigenetic regulation are potential drug targets and development of new tool compounds to validate these targets and understanding the dynamics of epigenetic marks is a key requirement in the field. Fortunately, this need is balanced by increasing activity and interest from the medicinal chemistry community as we hope this issue clearly demonstrates.

It is therefore highly appropriate that MedChemComm has decided to gather a web-based issue on epigenetic medicinal chemistry research. This issue contains more than 10 papers on epigenetic research with contributions as concise articles as well as reviews from leading groups in the field. These papers demonstrate the broadness of the field including inhibitors of HDACs, DNA methyltransferases, protein-protein interactions of reader domains, and looking at the enzymatic action of lysyl hydroxylases.

We are very pleased with this issue describing and demonstrating state-of-art within epigenetic medicinal chemistry and hope the readers of MedChemComm will enjoy it.

-Rasmus Prætorius Clausen (University of Copenhagen) and Mark Bunnage (Pfizer), Guest Editors

View the issue

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)

Top ten most accessed articles in November

This month sees the following articles in MedChemComm that are in the top ten most accessed:

Minisci reactions: Versatile CH-functionalizations for medicinal chemists
Matthew A. J. Duncton
Med. Chem. Commun., 2011, 2, 1135-1161
DOI: 10.1039/C1MD00134E

Towards biocompatible nanovalves based on mesoporous silica nanoparticles
Ying-Wei Yang
Med. Chem. Commun., 2011, 2, 1033-1049
DOI: 10.1039/C1MD00158B

Development of second generation epigenetic agents
Philip Jones
Med. Chem. Commun., 2012, Advance Article
DOI: 10.1039/C1MD00199J

Small molecules DNA methyltransferases inhibitors
Nadine Martinet, Benoît Y. Michel, Philippe Bertrand and Rachid Benhida
Med. Chem. Commun., 2011, Advance Article
DOI: 10.1039/C1MD00194A

Molecular obesity, potency and other addictions in drug discovery
Michael M. Hann
Med. Chem. Commun., 2011, 2, 349-355
DOI: 10.1039/C1MD00017A

Epigenetics — an emerging and highly promising source of new drug targets
Nessa Carey
Med. Chem. Commun., 2012, Advance Article
DOI: 10.1039/C1MD00264C

Synthesis of hybrid 4-anilinoquinoline triazines as potent antimalarial agents, their in silico modeling and bioevaluation as Plasmodium falciparum transketolase and ß-hematin inhibitors
Moni Sharma, Kuldeep Chauhan, Shikha S. Chauhan, Ashok Kumar, Shiv Vardan Singh, Jitendra K. Saxena, Pooja Agarwal, Kumkum Srivastava, S. Raja Kumar, Sunil K. Puri, Priyanka Shah, M. I. Siddiqi and Prem M. S. Chauhan
Med. Chem. Commun., 2012, 3, 71-79
DOI: 10.1039/C1MD00188D

Synthesis, thiol-mediated reactive oxygen species generation profiles and anti-proliferative activities of 2,3-epoxy-1,4-naphthoquinones
Allimuthu T. Dharmaraja, Tapan K. Dash, V. Badireenath Konkimalla and Harinath Chakrapani
Med. Chem. Commun., 2012, Advance Article
DOI: 10.1039/C1MD00234A

Inhibition of bromodomain-mediated protein—protein interactions as a novel therapeutic strategy
Silviya D. Furdas, Luca Carlino, Wolfgang Sippl and Manfred Jung
Med. Chem. Commun., 2012, Advance Article
DOI: 10.1039/C1MD00201E

2-Anilinonicotinyl linked 1,3,4-oxadiazole derivatives: Synthesis, antitumour activity and inhibition of tubulin polymerization
Ahmed Kamal, Y. V. V. Srikanth, Thokhir B. Shaik, M. Naseer A. Khan, Md. Ashraf, M. Kashi Reddy, K. Anil Kumar and Shasi V. Kalivendi
Med. Chem. Commun., 2011, 2, 819-823
DOI: 10.1039/C0MD00177E

Why not take a look at the articles today and blog your thoughts and comments below.

Fancy submitting an article to MedChemComm? Then why not submit to us today or alternatively email us your suggestions.

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)

Mini-review on aminoglycoside resistance caused by N-6′-acetyltransferase

Kenward Vong and Karine Auclair, McGill University, discuss the mechanism of AAC(6′)s – N-acetyltransferase enzymes that confer resistance to aminoglycoside resistance by catalysing the addition of an acetyl group from acetyl coenzyme A (AcCoA) to the 6′-N of aminoglycosides.  They also discuss aminoglycoside analogues designed to overcome AAC(6′)s and strategies for blocking AAC(6′)s.

Understanding and overcoming aminoglycoside resistance caused by N-6′-acetyltransferase
Kenward Vong and Karine Auclair
DOI: 10.1039/C2MD00253A

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)

Review: Advances in design and drug discovery of antimalarial peroxides

In this MedChemComm review article Professor Gary H. Posner and coworkers at The Johns Hopkins Malaria Research Institute (Baltimore, MD, USA) provide an up-to-date review of the design and antimalarial activity of cyclic peroxides.

The review covers:

  • antimalarial monomeric and dimeric derivatives of artemisinin
  • peroxides not derived from artemisinin
  • hybrides containing one peroxide unit covalently linked to a non-peroxide unit.

… and highlights the effectiveness and the symplicity of synthesis of these diverse cyclic peroxides.

Reference
Antimalarial peroxides: advances in drug discovery and design
Rachel D. Slack, Alexander M. Jacobine and Gary H. Posner
Med. Chem. Commun., 2012, Advance Article
DOI: 10.1039/C2MD00277A, Review

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)

Review: a unified mechanism for amphotericin B

Peter Kovacic and Andrew Cooksy examine the multiple modes of action and toxicity of this important antifungal antibiotic.

Areas covered:

Autoxidation and metabolism
Electron affinity
Pro-oxidant action
Drug activity and ROS-OS
Antifungal mechanism: ET-ROS-OS
Physiological action
Antioxidant activity
Toxicity
Conjugated dicarbonyls

Novel, unifying mechanism for amphotericin B and other polyene drugs: electron affinity, radicals, electron transfer, autoxidation, toxicity, and antifungal action.
Peter Kovacic and Andrew Cooksy
DOI: 10.1039/C2MD00267A

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)

Issue 1 2012 just published!

Happy New Year to all our readers and welcome to our first issue of 2012!

On the cover of this issue is work by John Spencer et al. on the synthesis of a small library of ferrocene-based HDAC inhibitors via click chemistry – click JAHAs.  This article is from our forthcoming web collection on Epigenetics, take a look at some of the other interesting articles published in this series.

Click JAHAs: conformationally restricted ferrocene-based histone deacetylase inhibitors
John Spencer, Jahangir Amin, Ramesh Boddiboyena, Graham Packham, Breeze E. Cavell, Sharifah S. Syed Alwi, Ronald M. Paranal, Tom D. Heightman, Minghua Wang, Brian Marsden, Peter Coxhead, Matthew Guille, Graham J. Tizzard, Simon J. Coles and James E. Bradner.
DOI: 10.1039/C1MD00203A

Also in this issue are reviews on polyamine-based epigenetic modulators, Stat5 signalling inhibitors, protein structure-based pharmacophore modeling and hot papers on the inhibition of E. coli DXP synthase and a glucuronide prodrug of doxorubicin.

View the rest of the issue here

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)

Chagas disease: selenosemicarbazones as new leads to beat drug resistant parasite

Scientists from Uruguay and the US have made new compounds that could be used to treat Chagas disease. Chagas disease is a parastic disease caused by the protozoan Trypanosoma cruzi. It affects an estimated 10 million people in South and Central America and results in 20 000 deaths each year.

The cysteine protease cruzipain is an essential T. cruzi enzyme and is one of the few validated drug targets for the disease. Current treatments include Nifurtimox and Benznidazole, but the cruzipain is becoming resistant to them.

Thiosemicarbazones have been described as cruzipain inhibitors. Now, the team have replaced the sulfur in these compounds with selenium to make selenosemicarbazones to find new drug leads. The selenosemicarbazones showed enhanced cysteine protease inhibitory activity compared to the thiosemicarbazones and to Benznidazole, one of the two current drugs on the market.

Selenosemicarbazones as Potent Cruzipain Inhibitors and their Antiparasitic Properties against Trypanosoma cruzi
Chiara Pizzo, Paula Faral-Tello, Gustavo Salinas, Martín Fló, Carlos Robello, Peter Wipf and Graciela Mahler
Med. Chem. Commun., 2011, Accepted Manuscript
DOI: 10.1039/C2MD00283C

Research on the Chagas and neglected diseases was also recently the subject of MedChemComm’s latest poster prize.

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)

Meet the MedChemComm team

The MedChemComm team will be attending a number of conferences in 2012 and we would be delighted to meet you.

Dr Marie Cote, Deputy Editor

Dr Richard Kelly, Managing Editor

Here are just some of the conferences where you can meet us in the coming months:

Please let us know if you are planning on attending any of these meetings, as it would be lovely to meet you there!

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)