From Tropical Diseases to Counterfeit Drugs: The Diversity of Medicinal Chemistry

Interview with Prof. Dr. Ulrike Holzgrabe

27. 1. 2012 | The professor of medicinal and pharmaceutical chemistry at the Würzburg University develops active ingredients for medicines, detects counterfeit drugs and helps to fight infectious diseases.
AcademiaNet: Prof. Holzgrabe, you hold the chair of pharmaceutical chemistry at the Würzburg University. One of your specialities is medicinal chemistry. What is this field all about?

In medicinal chemistry, we develop drugs. We start out by identifying the structures whose malfunction cause diseases in humans, usually proteins. Stimulating or inhibiting the protein function can result in an effective therapy of an illness, or it can at least relieve symptoms. Originally small molecules were used as stimulators or inhibitors; increasingly, larger molecules like antibodies are employed. First, we identify target structures concerning their biological and structural properties. Next, we aim to develop inhibitors or stimulators that could be used as an active ingredient, after extensive processes of optimisation.

Prof. Holzgrabe
Bild vergrößern
(© Ulrike Holzgrabe / Universität Würzburg)

Prof. Holzgrabe

In the development of new active pharmaceutical ingredients (APIs), the following fields work hand in hand: synthetic organic chemistry, structural biology, molecular biology and pharmacology. All of these contribute to medicinal chemistry, and often the borders of a scientific field cannot be defined clearly. Research in medicinal chemistry on an academic level is often carried out in Collaborative Research Centres, like our SFB 630 (Recognition, Preparation, and Functional Analysis of Agents against Infectious Diseases) financed by the German Research Foundation (DFG). At the centre, we are searching for drugs against tropical infectious diseases. We have structural and infection biologists, physicists, pharmacologists and chemists cooperating on this topic. So obviously, medicinal chemistry is an interesting as well as a very interdisciplinary subject.

Among other topics, you research active ingredients against tropical diseases. Can you report on some findings?

After eight years of research, we have identified three or four drug candidates at our centre. Currently they are being characterised in animal experiments on a preclinical level: their efficacy, toxicity, their pharmacokinetics and metabolisms need to be determined.

At this stage, we already require dosage forms for animals. We are optimistic that we will test at least one of these agents in clinical trials. I would like to emphasise that we also conduct extensive fundamental research at the SFB, especially in the field of infection biology; the research on drugs will benefit later.

You are one of the few female pharmaceutical chemists who are regularly quoted in the press. When it comes to counterfeit medicines, you are in the front line as an expert on quality assurance in medicine. Which persons are especially at risk to suffer from counterfeit drugs?

When I accepted the chair of pharmaceutical and medicinal chemistry in 1999, I also started to be involved in the quality analysis of active pharmaceutical ingredients. In addition to the professorship, I also followed my predecessor's footsteps by joining several committees concerning themselves with the rules and methods of analysing active ingredients, like the European Directorate for the Quality of Medicines. Soon I was part of the almost investigative detection of counterfeit ingredients.

These counterfeit medicines are usually ordered via the internet and are often lifestyle drugs like the potency-enhancing drugs Viagra® and Cialis®. The same holds true for bodybuilding products, which are often sold in the respective studios. Here the counterfeit rate is almost fifty percent. Since the distribution chain from the producer right down to the single pharmacy is strictly controlled, you are pretty safe from dangerous counterfeit products if you buy drugs in a pharmacy.

Nevertheless, there have been counterfeiting incidents concerning therapeutic medicines in the last few years. The scandal about the anticoagulant drug Heparin has kept the pharmaceutical world in suspense: It had been deliberately contaminated with a substance that could lead to anaphylactoid shocks – solely for cost reduction. This won't be the last case, because the European and the American pharmaceutical industry have relocated more than eighty percent of their production to China and India, and in both countries production is sometimes difficult to control.

In order to tackle this problem locally, you are cooperating with African partners. Who are these partners, and how does this cooperation work?

In Africa, medicine counterfeiting is almost ubiquitous. In states like Ghana and Nigeria, the counterfeit rate is higher than fifty percent. Most of these products come from India. We are currently establishing a network with Ghana, Tanzania and Cameroon to qualify staff members in the local healthcare systems in the analysis of active ingredients. On an academic level, we cooperate with Universities, but we also work with local authorities and medicine distribution centres. The grant applications have been filed, now we are waiting for their approval.

In Europe, the controls are strict. But over the internet and with long-distance travel, there are still certain health risks from counterfeit medicines. When and where should patients be especially careful?

Patients should buy their drugs in their pharmacies, as I said before. If you are planning to leave Europe, try to take all relevant medicines along and don't feel tempted to buy cheaper medicines abroad. In this respect, "Europe" ends at the Greek-Turkish border, sometimes even in Poland. If you buy Aspirin in Mexico, you have no guarantee that the drug will contain any active ingredient at all – the counterfeit rate in Mexico is roughly thirty percent.

Pharmacy is considered a women's domain. Does this hold true for pharmaceutical chemistry as well?

Pharmacies are considered to be family-friendly workplaces, and they indeed are mostly women's domains. This corresponds to our student numbers: up to seventy percent of our students are female. In the past, we often were accused of training too many students that never entered the workforce. But this is less and less the case, for numerous female pharmacists work part-time after having children, and start working full-time again later. Still there is a shortage of pharmacists, so pharmacy is a very promising field of study. Furthermore, this degree enables students to later work in numerous professional environments: in the pharmaceutical industry, in control authorities, in health insurance companies, in Universities, for the military, as a science writer, etc. And in all of these areas, the women to men ratio is much lower.

In my field of pharmaceutical and medicinal chemistry, only fifteen percent of the professors are female. This is also true for the other pharmaceutical fields like pharmaceutical technology and biology or clinical pharmacy, pharmacology and toxicology. But women are catching up! When I accepted a professorship for pharmaceutical chemistry in Bonn in 1990, I was the only female professor for this subject in Germany. Now, there are four or five of us...

Dear Prof. Holzgrabe, thank you very much for this Interview.

Interview: Elke Reinecke
Translation: Susanne Dambeck   (© AcademiaNet)

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