Chemistry trick renews hope against killer diseases – University of Copenhagen

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23 December 2011

Chemistry trick renews hope against killer diseases

As infections such as tuberculosis have become immune to an ever widening range of antibiotics, doctors have looked on helplessly.
Now a Danish chemist has pioneered a novel way to battle multidrug resistant bacteria. By tweaking a well known psychoactive drug he revitalizes worn-out drugs like sulpha and penicillin.

Brain drug to boost antibiotics 

Chemist Jorn Bolstad Christensen of the University of Copenhagen has patented the use of schizophrenia medication Thioridazin in boosting the effect of antibiotics. Christensen is an associate professor at the Department of Chemistry and in the lab he started investigating how the schizophrenia drug might bother bacteria but not humans.
"Thioridazin blocks the capacity of bacteria to cleanse themselves of antibiotics. We knew that before starting. But I wanted to remove the action of the drug in the brain so that mortally ill tuberculosis patients wouldn't have to contend with psychoactive effects as a part of their cure," explains Christensen, who none the less had to come to terms with a much bigger threat as well.

Bacteria and humans too alike for comfort

Bacteria such as those responsible for tuberculosis, staphylococcus and enterococcus get rid of antibiotics using their so called efflux-pump. A mechanism which simply pumps the active substance out of the cell before it has an opportunity to do harm. A substance which blocks the pump should ensure that any antibiotic stays inside the bacteria long enough to kill it. There's just one tiny problem. Human cells have efflux pumps as well. And we wouldn't want these blocked.

Mirrored images quite unlike each other

Though the problems of blocking the efflux pump of human cells appeared solved Professor Christensen still needed to minimize the psychoactive effects of the drug. This was where his chemical expertise became indispensable. Chemically Thioridazin consists of two molecules which are perfect mirror images. One of these mirror- or isomeric forms affects the brain less than the other, so the question was whether bacteria would know the difference.