Promising compounds which may help patients overcome drug addictions have been identified by US scientists. 

Drug abuse causes long-term chemical changes in the brain which remain many years after the abuse has stopped. These changes maintain a 'memory' of the addiction leaving patients vulnerable to relapse. Recently researchers at Duke University, North Carolina, have found that an enzyme usually present in the brain, PKC-, appears in increased concentrations in cocaine-sensitised rats, suggesting that it plays a key role in this memory process. 

Jiyong Hong and colleagues intend to develop therapeutic compounds that target this enzyme to help people 'forget' their drug dependence. 'A patient has some memory of using a drug,' explains Hong, 'and we aim to erase that memory by inhibiting PKC-'. This poses a significant challenge, says Hong, since compounds that can selectively target specific forms of PKC are rare.

Benzopyranone compounds have been identified as possible therapeutics for drug dependency

Undeterred by this, and passionate about the social impact of this work, the team tested over 1000 different compounds for their ability to inhibit PKC- function and found three suitable benzopyranone candidates. They then used computer modelling to determine the interactions behind the compounds' inhibitory activity. With this knowledge, Hong aims to subject these compounds to a process of directed evolution: creating a library of compounds based upon this scaffold and selecting those compounds which show enhanced activity as the bases of new libraries.

Nathanael Gray, an expert in PKC function at Harvard University, Massachusetts, US, agrees that these results represent a promising start. However, he emphasises the need to 'know about cellular activity and the broader selectivity profile versus other enzymes given that this scaffold is capable of having numerous other activities.'

Hong is also well aware of this: 'We now want to expand the enzyme panel to see just how selective the compounds are and to optimise the potency and selectivity before, ultimately, performing an in vivo study,' he says.   

Philip Robinson

Enjoy this story? Spread the word using the 'tools' menu on the left or add a comment to the Chemistry World blog.