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A Way Forward In Developing Medicines With Fewer Unwanted Side Effects

A breakthrough study has shown a way forward to create medicines/drugs which have fewer unwanted side effects than we have today


 

Medicines in today’s times comes from a variety of sources. Side effect in medication is a big headache. The unwanted side effects in medicines which are either rare or common are majorly annoying and sometimes can be very serious. A medicine which has no or fewer mild side effects can be used by a larger majority of people and will be tagged as much safer. Medicines which have more serious side effects can be used only in circumstances where no other alternative is available and would also require monitoring. Ideally, medicines which have fewer or no unwanted side effects shall be a boon for medical therapy. It’s a major goal and also a challenge for researchers worldwide to develop new medications which contain no serious side effects.

The human body is a very complex structure built from chemicals which need to be regulated for smooth functioning of our system. Most medicines consist of a mix of chemical compounds. These chemical compounds are composed of molecules. The important molecules are called “chiral molecules” or enantiomers. The chiral molecules look identical to each other and contain the same number of atoms. But they are technically “mirror images” of each other i.e. one half of them are left-handed and the other half are right-handed. The important aspect here is this difference in their “handedness” leads them to produce different biological effects. This difference has been studied thoroughly and it has been pointed out that the correct chiral molecules are extremely important for a medicine/drug to make the correct impact, otherwise “wrong” chiral molecules can produce undesired results. The separation of chiral molecules is a very crucial step for drug safety. This process if not simple, is quite expensive and generally requires customized approach for each molecule type. Lot of research has been conducted in this area, but it has failed to develop a cost-effective simplistic separation process. Therefore, we are still far away from a time when all medicines on the shelf at a pharmacy will contain no side effects.

Looking at why medicines have side effects

In a recent study published in Science, researchers from Hebrew University of Jerusalem and Weizmann Institute of Science have discovered a uniform non-specific method by which the separation of left and right chiral molecules in a chemical compound can be achieved easily in a cost-effective manner1. Their work sounds very pragmatic and simple. The method which they have developed is based upon magnets. Chiral molecules interact with a magnetic substrate and assemble according to the direction of their “handedness”. That is, “left” molecules interact with a particular pole of the magnet, while “right” molecules interact with the other pole. This technology sounds logical and useful and can be used by chemical and pharmaceutical manufacturers to keep the good molecules (whether left or right) in a medicine and remove the bad ones which are responsible for causing harmful or undesired side effects.

Improving medicines and more

This is definitely a breakthrough study and will play a major role in developing better and safer drugs using simple and cost-effective separation method. Some popular drugs today are sold in their chirally-pure forms (i.e. separated form) but this statistic stands at only about 13% of all drugs available in the market. Thus, separation is highly recommended by drug administration authorities. Revised guidelines must be met by pharmaceutical companies to incorporate this and make medicines that are more safe and reliable. This study could play a role beyond medicines and also for food ingredients, food supplements etc. Following such guidelines could elevate the quality of food products and can help improve lives. This study is also very relevant for chemicals used in agriculture - pesticides and fertilizer- because chirally separated agrochemicals will cause less contamination to the environment and will contribute towards higher yields. This simple separation carried out for chemical compounds (which are to be consumed) has surprisingly a long list of goodness attached to it and will be a boon to many sectors .

Another study done by researchers at Australian National University has shown how understanding the molecular details of how drug or medicine works can help us to find a way to reduce unwanted side effects in them2. The team of researchers for the first time specifically carried out studies at molecular levels to look for similarities across six pharmaceutical drugs which are used for pain relief, dentist anesthetic and in treatment of epilepsy. They ran bigger and more complex computer simulations using supercomputers to map the picture of how these drugs were behaving. They mapped clues about molecular details on how these drugs might be affecting one part of the body and would unintendedly cause an undesired side effect in another part of the body. Such molecular level understandings can critically guide scientists and they must be incorporated in all drug discovery and design studies. This also brings about the possibility of modifying the structure of existing drugs or making new drugs which would have reduced unwanted side effects.

Do these studies mean there will be a day very soon where medicines will have no side effects whether mild or serious. Maybe not so soon, because our body is a highly complex system and many mechanisms in our body are interlinked to each other. However, these studies have led to a promising conclusion that firstly there is hope to have medicines or drugs which have very few and mild side effects which are well-understood. Secondly, the serious side effects of medicines if there should be understood as well and medical practitioners will have access to more information on how the prescription and sale of such medicines is brought under control to avoid fatalities.

Source

  1. Banerjee-Ghosh, Koyel et al 2018, ‘Separation of enantiomers by their enantiospecific interaction with achiral magnetic substrates’, Science, eaar4265, DOI: https://doi.org/10.1126/science.aar4265
  2. Amanda Buyan, Delin Sun, Ben Corry 2018, ‘Protonation state of inhibitors determines interaction sites within voltage-gated sodium channels’, Proceedings of the National Academy of Sciences, vol. 115, no.14,
    DOI: https://doi.org/10.1073/pnas.1714131115

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Vol.1 Issue 6 June 2018

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