Molecular modelling to help create better, safer drugs

May 24, 2013
Molecular modelling to help create better, safer drugs

(Phys.org) —How our bodies break down the common drugs ibuprofen, diclofenac and warfarin is the subject of a new study from the University of Bristol, published in the Journal of the American Chemical Society. The research should ultimately help predict how new drugs will be metabolized in the body, potentially helping avoid adverse drug reactions in future.

Professor Adrian Mulholland of the School of Chemistry and colleagues used molecular modelling to show in atomic detail how ibuprofen, diclofenac and are broken down by a group of enzymes called cytochrome P450s which play an important part in the metabolism of drugs.

Cytochrome P450s break down drugs by adding to them, thus making them more soluble in water and easier to remove from the body. It's important that drugs are broken down in this way so they don't accumulate to toxic levels. However, it's also important that the drugs aren't broken down too quickly otherwise they won't stay in the body long enough to work.

Different people have different types of P450 which mean they break down drugs more quickly or more slowly. Potentially harmful complications can also sometimes occur, for example, other drugs can 'block up' P450s thus interfering with the metabolism of a particular drug. Other substances can also interfere with the process, for example grapefruit and contain a molecule that 'inhibits' some cytochrome P450s, preventing them from breaking down drugs. This can cause the drug to build up to a toxic – and possibly lethal – level.

Professor Mulholland said: "An important aim in developing a safe, effective drug is understanding how it will be broken down in the body. This process would be made quicker, cheaper and safer if we could predict reliably – for example, by using computers – how a candidate drug reacts in the body.

"This study uses molecular modelling methods which are able to describe chemical reactions in large and complex enzymes such as cytochrome P450s. Our results agree well with experiments, and point to how modelling of this sort can help in developing predictions of drug metabolism."

Explore further: Achieving chemical-free natural cosmetics with the power of enzymes

More information: Lonsdale, R. et al. QM/MM Modeling of Regioselectivity of Drug Metabolism in Cytochrome P450 2C9, Journal of the American Chemical Society. pubs.acs.org/doi/abs/10.1021/ja402016p

add to favorites email to friend print save as pdf

Related Stories

New research increases understanding of drug metabolism

Mar 17, 2010

Research led by Wayne L. Backes, PhD, Professor of Pharmacology and Associate Dean for Research at LSU Health Sciences Center New Orleans School of Medicine, has found that drug metabolism depends not only upon which enzymes ...

New insight into how 'tidying up' enzymes work

Mar 28, 2011

A new discovery about how molecules are broken down by the body, which will help pharmaceutical chemists design better drugs, has been made by researchers at the University of Bristol.

Organovo announces ability to print 3D human liver tissue

Apr 24, 2013

(Medical Xpress)—Organovo Holdings, Inc., a company that designs and creates functional human tissue has announced at this year's Experimental Biology Conference that it has developed a 3D printing technique ...

Recommended for you

User comments : 0