RSC Medicinal Chemistry Blog

Issue 2 now online including hot articles on epigenetics

06 Feb 2012

On the cover of this month’s issue is an article from our Epigenetics collection from Manfred Jung, looking at the potential of small molecule inhibitors of acetyl lysine–bromodomain interactions.

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

The issue also contains several other epigenetics articles on second generation epigenetic agents, epigenetics as a source of new drug targets and thiobarbiturates inhibitors. The epigenetics issue was guest edited by Rasmus Prætorius Clausen (University of Copenhagen) and Mark Bunnage (Pfizer) – read their introduction to the issue.

View Issue 2

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Have you seen our recent review articles? Papers on molecular obesity, telomeres targetted with natural products and minisci reactions

03 Feb 2012

By Francesca Burgoyne.

During 2011 we published a number of topical reviews on a wide range of topics by expert researchers in their fields. We’ve collected them below and we hope you’ll find something interesting in your area!

Molecular obesity, potency and other addictions in drug discovery
Michael M. Hann
DOI: 10.1039/C1MD00017A

Proteochemometric modeling as a tool to design selective compounds and for extrapolating to novel targets
Gerard J. P. van Westen, Jörg K. Wegner, Adriaan P. IJzerman, Herman W. T. van Vlijmen and A. Bender
DOI: 10.1039/C0MD00165A

Impact of ion class and time on oral drug molecular properties
Paul D. Leeson, Stephen A. St-Gallay and Mark C. Wenlock
DOI: 10.1039/C0MD00157K

Novel, unifying mechanism for aromatic primary-amines (therapeutics, carcinogens and toxins): electron transfer, reactive oxygen species, oxidative stress and metabolites
Peter Kovacic and Ratnasamy Somanathan
DOI: 10.1039/C0MD00233J

Natural products targeting telomere maintenance
Jack Li-Yang Chen, Jonathan Sperry, Nancy Y. Ip and Margaret A. Brimble
DOI: 10.1039/C0MD00241K

The p53-MDM2/MDMX axis – A chemotype perspective
Kareem Khoury, Grzegorz M. Popowicz, Tad A. Holak and Alexander Dömling
DOI: 10.1039/C0MD00248H

Computational ligand-based rational design: role of conformational sampling and force fields in model development
Jihyun Shim and Alexander D. MacKerell, Jr.
DOI: 10.1039/C1MD00044F

Expanding the horizon of chemotherapeutic targets: From MDM2 to MDMX (MDM4)
Antonio Macchiarulo, Nicola Giacchè, Andrea Carotti, Fabiola Moretti and Roberto Pellicciari
DOI: 10.1039/C0MD00238K

Progress on lamellarins
Daniel Pla, Fernando Albericio and Mercedes Álvarez
DOI: 10.1039/C1MD00003A

Are pyridazines privileged structures?
Camille G. Wermuth
DOI: 10.1039/C1MD00074H

Towards biocompatible nanovalves based on mesoporous silica nanoparticles
Ying-Wei Yang
DOI: 10.1039/C1MD00158B

Minisci reactions: Versatile CH-functionalizations for medicinal chemists
Matthew A. J. Duncton
DOI: 10.1039/C1MD00134E

If you have an idea for a review article that hasn’t been covered and you would like to see included, contact the Editorial Office – we’d love to hear from you.

You can also find the collection here.

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Themed issue on epigenetics just published

31 Jan 2012

By Francesca Burgoyne.

We are delighted to announce the publication of a themed issue on epigenetic medicinal chemistry, guest edited by Rasmus Prætorius Clausen and Mark Bunnage, covering recent developments of this important and growing field.

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

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

18 Jan 2012

By Francesca Burgoyne.

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

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Review: Advances in design and drug discovery of antimalarial peroxides

11 Jan 2012

By Marie Cote, Deputy Editor.

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

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Review: a unified mechanism for amphotericin B

11 Jan 2012

By Francesca Burgoyne.

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

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Issue 1 2012 just published!

06 Jan 2012

By Francesca Burgoyne.

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

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

05 Jan 2012

By Marie Cote, Deputy Editor.

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.

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Meet the MedChemComm team

03 Jan 2012

By Marie Cote, Deputy Editor.

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:

Zing conference on Natural Products Synthesis and Biosynthesis – 10-13 February, Lanzarote, Spain – Meet Marie
Gordon Research Conference on Marine Natural Products – 26 Feb.- 02 March, Ventura, USA – Meet Richard
Keystone sympoium on Addressing the Challenges of Drug Discovery – 19-23 March, Tahoe City, USA – Meet Marie
BTS Annual Congress 2012 – 25-28 March 2012, Warwick, UK – Meet Richard
OBC Symposia, touring Shanghai, Lanzhou and Beijing – 14-21 April, China – Full details coming soon… – Meet Richard
48th EUROTOX Congress – 17-20 June, Stockholm, Sweden – Meet Nicola Wise, Business Development Executive
Gordon Research Conference on Heterocyclic Compounds – 24-29 June, Salve Regina University, USA – Meet Marie
BOSS XIII – 13th Belgium Organic Synthesis Symposium – 15-20 July, Leuven, Belgium – Meet Marie
ASIATOX VI – 17-20 July, Sendai, Japan – Meet Richard
244th ACS National Meeting, 19-23 August, Philadelphia, USA – Meet Richard
ISMC 2012 – 22nd International Symposium on Medicinal Chemistry – 02-06 Sept., Berlin, Germany – Meet Marie
ICPOC 21 – 21st IUPAC International Conference on Physical Organic Chemistry – 09-13 Sept., Durham, UK – Meet Marie

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

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RSC Medicinal Chemistry Blog

Issue 2 now online including hot articles on epigenetics

Have you seen our recent review articles? Papers on molecular obesity, telomeres targetted with natural products and minisci reactions

Themed issue on epigenetics just published

Top ten most accessed articles in November

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

Review: Advances in design and drug discovery of antimalarial peroxides

Review: a unified mechanism for amphotericin B

Issue 1 2012 just published!

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

Meet the MedChemComm team

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