New Way to Stabilize Chiral Molecules in Drug Applications

Posted by Alex Brown on March 17th, 2016

Scientists developed a method to stabilize the chiral compounds and make them functions without unwanted side effects. Now the technology is working on a drug-thalidomide-against sleep problems and the engineered thalidomide drug is still under clinical trials for safety testing.

Chiral compounds are two compounds with mirror structures, but with different chemistry characters. Generally, one is more active than the other as for the treatment of a single condition and the inactive one may bring some side effects. The problem the modern chiral synthesis technology faced with is the separation. Up to present, an effective way to produce one pure chiral compound is of great difficulty and yet to be probed for an easy version. However, the thorniest issue for this is that the two enantiomers would racemize in the storage or metabolism stages though they are produced singly. That’s why many drugs are still developed in the form of racemates.

Thalidomide would be a typical material for this research. Early to 1950’s, it was found with the medical ability to release morning vomiting and insomnia; then it’s applied by many pregnant women in their early pregnancy against morning sickness. However, it’s recorded afterwards that a relative high ratio of women who took the thalidomide in racemates form gave birth to babies with deformity mainly in limbs as they generally took the drug at the stage when limbs were formed. The accidents raised the attention on gaining more knowledge of chiral analogs.

Scientists successfully addressed the racemization problem by substitute the unstable hydrogen protons at the chiral center with deuterium, which slows the process of proton exchange for racemization and spares time for the drug elimination before that happen. Besides the proton exchange also makes the two compounds-CC-11006 and CC-122 more stable and easy to be studied as the latter compound is researched for its potential in related cancer treatment.

Before the success, other substances were tried for the substitution, but no ideal result was achieved, until the application of deuterium, a much heavier isotope of hydrogen. Right because of the weight, the bond can be stronger than that made of hydrogen, and then detour the racemization process with no extra influence on its pharmaceutical performance.

The usage of deuterium in chiral switching will enable many other drugs presented in the form of racemates get rid of the side effects and be applied by making full of its medical advantages, providing more possibilities for the present drugs in racemates form.

References:

Sometimes, heavier drugs are safer- Isabel Perez Castro

Differentiation of antiinflammatory and antitumorigenic properties of stabilized enantiomers of thalidomide analogs, DOI: 10.1073/pnas.1417832112.

Chirality-Wikipedia