Improving the medicine

As we saw earlier, nature often makes some interesting molecules that can be useful for people. Equally, scientists can develop useful new molecules in the laboratory. However, they aren't always perfect.

Do you think that have enough willow trees in the world to meet the global demand for aspirin? How large do you think a laboratory would need to be to grow all of the Penicillium notatum needed to produce a global supply of penicillin?

If scientists can develop time and money efficient methods for developing medicines in a laboratory, we can reduce the environmental impact of pharmaceutical production.

Did you notice that in 1897, a chemist altered the natural product salicylic acid by adding a functional group, thus reducing the side effects of the medicine?

If we understand the chemistry behind pharmaceuticals, we can alter them to create desired properties. For example:

• improve the binding of the molecule to the receptor for longer term, stronger effects

• improve absorption into the body, therefore lowering the dose required and reducing unwanted side effects

• change the administration route by altering the solubility of the molecule, allowing patients to use oral tablets instead of injections

• reduce side effects by reducing the ability of the medicine to bind to the wrong receptor

• reduce the cost of the medicine by finding a cheaper way to synthesise it

• create new versions of a medicine that the pathogen is not yet resistant to

Scroll down to see some examples of medicines that have been altered by scientists over time.

As we saw on the previous page, Artemisinin is a natural product derived from sweet wormwood that is used to treat malaria. Artemisinin kills malaria parasites quickly, and is able to kills them in all of their lifecycles.

However, has poor pharmacokinetics (absorption, bioavailability, distribution, metabolism, excretion), in particular low bioavailability, meaning it doesn't absorb well into the body and only a small proportion of the medicine becomes available to kill the parasite. It is also really costly to produce.

Below you can look at some of the analogues (molecules with similar structure) of artemisinin. Look at the skeletal structure of these medicines.

What do you think the most important part of the molecule is for killing malaria parasites? The part of the chemical structure that is responsible for the medical activity is called the pharmacophore.

What do you think the effect of changing the side chains is?

Which of these three molecules are better treatment options? Why?

Which ones would you put on the Essential Medicines list?

Different types of penicillins are synthesised to change their activity profile.

Can you guess the structure of penicillin's pharmacophore from looking at the structures below?

New methods of drug design involve determining the structure of target proteins, enzymes or receptors using X-ray crystallography and using computer modelling to predict new structures of molecules that might bind to and activate or block those targets.

1. In your own words, define the terms:

a. pharmacophore

b. side chain

2. Why do scientists alter the side chains of medicines that they already know are functional?