RSC Medicinal Chemistry Blog

Israeli scientists have developed compounds that could be better treatments for genetic diseases than current drugs.

Timor Baasov and his colleagues at the Israel Institute of Technology have improved compounds used to suppress faults in genes called nonsense mutations.

Nonsense mutations, which cause more than 1800 human diseases, are alterations in the genetic code that stop protein production prematurely, leading to truncated or nonfunctional proteins. Gene therapy is one treatment, but it’s had limited success. With suppression therapy, small molecules allow cells’ protein producing equipment to skip over nonsense mutations to restore the proteins. Aminoglycosides – antibiotic amine-modified sugars – are the only clinically available drug family known to be effective in suppression therapy, but at effective doses, the compounds have high human toxicity.

Two aminoglycoside derivatives were found to suppress alterations in the genetic code called nonsense mutations

Read the full story in Chemistry World
 
Link to journal article
Repairing faulty genes by aminoglycosides: Identification of new pharmacophore with enhanced suppression of disease-causing nonsense mutations
Jeyakumar Kandasamy, Dana Atia-Glikin, Valery Belakhov and Timor Baasov,
Med. Chem. Commun., 2011, DOI: 10.1039/c0md00195c

MedChemComm article by Chung Sung-kee and co-workers has been highlighted in The Korea Herald.

A group of South Korean researchers said Monday that they found a way to use drugs to fight brain tumors that are currently treated with only surgery and chemotherapy.

You can read the whole story here and also download the article which is free to access here.

Preparation of blood-brain barrier-permeable paclitaxel-carrier conjugate and its chemotherapeutic activity in the mouse glioblastoma model
Juyoun Jin, Woo Sirl Lee, Kyeung Min Joo, Kaustabh K. Maiti, Goutam Biswas, Wanil Kim, Kyong-Tai Kim, Se Jeong Lee, Kang-Ho Kim, Do-Hyun Nam and Sung-Kee Chung
Med. Chem. Commun., 2011
DOI: 10.1039/C0MD00235F

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