Natural compounds are a very important source of new drugs
José Pichel Andrés/DICYT The chemical substances present in living creatures such as plants and animals are one of the main sources of drugs, in addition to other products from various fields ranging from food to cosmetics. At the Faculty of Pharmacy of the University of Salamanca, the researcher Marina Gordaliza has been devoted to the study of these natural compounds for years in collaboration with various companies; she is currently concentrating on the detailed analysis of data from this field, which indicates its growing relevance.
About half of the drugs available nowadays are related to natural compounds, and in the case of cancer this figure exceeds 60%. Despite everything, “for a time the pharmaceutical industry turned away from them”, the researcher pointed out to DiCYT, probably because it was more advantageous to manufacture synthetic products.
Obtaining access to natural molecules, which is many cases may even be found at the bottom of the sea, isolating them, or attempting to produce them in large quantities may be hard work. However, in recent years "time and cost is being optimised”. Perhaps for this reason, they have been gaining ground in the world of pharmacology for decades.
Newman and Cragg analysed the origin of 1,330 new small-molecule chemical products approved as drugs between 1981 and 2010 and found that 64% had some connection with natural compounds. If vaccines and biotechnological products are included the percentage rises to 71%, and of the 175 new anti-cancer drugs approved during this period 131 are natural compounds or are related to them, i.e. 75%.
It is not therefore surprising that many of the most frequently prescribed drugs have a natural original. Atorvastatin for instance, which is used to combat high cholesterol levels, is related to natural compounds such as lovastatin. Morphine comes from the opium plant and has many derivatives that are used as painkillers, and even the popular aspirin comes from salicyclic acid, a compound deriving from the willow.
In these and in many other cases, the researchers take the natural compound as a starting point and try to manipulate it to improve its pharmacological activities and eliminate possible adverse effects. This is what is known as “pharmacomodulation”.
By means of a detailed analysis of this type of data, Marina Gordaliza is studying “the patterns and strategies that have been followed over time to introduce these compounds in the therapeutic field”, although the conclusions can often be extended to other bioactive products such as pesticides in the case of agriculture. Proposals that are interesting to experts can be made from the conclusions of the analysis.
The potential of the sea
One of the fields that is currently most fashionable and is arousing much interest owing to its great potential is that of the natural substances to be found in the sea. “The oceans represent over 70% of the surface area of the Earth and the marine ecosystem some 95% of the biosphere, but there is another important statistic: 60% of the marine compounds studied show significant biological activity”, the researcher points out.
Life at great depths requires the withstanding of high hydrostatic pressures, variable temperatures, and low levels of oxygen and light, which means that their inhabitants “adapt all their biochemical machinery to face extreme conditions, thus generating powerful substances”. Under these conditions marine species develop what are technically known as “privileged structures” to face unfavourable circumstances.
The first drug of marine origin was approved only a decade ago. This product, ziconotide, is suitable for treating chronic pain. The next was trabectedin, the first anti-tumour drug of Spanish marine origin, which was developed by the company Pharmamar from the mangrove tunicate Ecteinascidia turbinata. The product is used to treat the sarcoma of soft tissues and relapses from ovarian cancer.
A very significant detail is that “of over 30,000 natural marine compounds published, less than 2% originate in the depths”, which means that there is a very great deal of biodiversity of both animals and plants still to be discovered. As the researchers gain access to this great potential the number of natural compounds and their applications will be able to multiply.
In order to study these matters in more detail, for four years the Faculty of Pharmacy and the Institute for Science and Technology Studies (Instituto de Estudios de la Ciencia y la Tecnología, IECyT) organised ‘Symposiums on medicinal plants and natural compounds as sources of new drugs’, in which top speakers analysed various aspects of this field. The last edition was held in 2010 but the idea may be revived, especially given the idea of disseminating the latest advances on natural compounds to students of the University of Salamanca.