Boije af Gennäs, Gustav

Boije af Gennäs, Gustav
Drug Research Program, Faculty of Pharmacy, University of Helsinki

Dr. Gustav Boije af Gennäs is a Principal Investigator of the Drug Discovery Group at the Faculty of Pharmacy, University of Helsinki. His main research interests include regenerative medicine, inhibitors of pathogenic parasites, cancer, therapy of Alzheimer’s and Parkinson´s diseases and the development of microchip technology. Dr. Boije af Gennäs has published over 20 peer-reviewed scientific articles, two patents, and supervised 5 PhD and 18 MSc students. Currently he leads a group of 4 PhD and 2 MSc students in the Synthetic Medicinal Chemistry group that uses state-of-the-art methods in the design and synthesis of novel drug-like compounds, such as stem cell inducers as well as kinase and other enzyme inhibitors and activators. In addition, he develops microchips for novel applications such as bioanalysis and organic reaction analysis.
Dr. Boije af Gennäs has been the head of several research projects including those funded by the Academy of Finland and the University of Helsinki, and is involved in projects funded by the Finnish Funding Agency for Technology and Innovation (TEKES), EU, Jane and Aatos Erkko Foundation etc. He has had several invited plenary and keynote presentations in international and national scientific conferences. Dr. Boije af Gennäs is a board member in international scientific committees, evaluation panels and societies. In 2012 he was granted the highly distinguished Academy of Finland postdoctoral project that was continued by the Key Project Funding in 2016. In addition, he received the University of Helsinki Three-year-grant in 2016 and obtained the Finnish Society of Sciences and Letters Award by the Ruth and Nils-Erik Stenbäck Foundation as well as the Young Researcher Award by the University of Helsinki, both in 2016.

Design and Synthesis of Novel Inhibitors Targeting Pathogenic Protozoan Parasites

Malaria and leishmaniasis are caused by protozoan parasites that are responsible of major morbidity and mortality across the world, and new specific therapies are greatly needed. Several of the diseases associated to protozoan parasites are classified as “neglected diseases” by The World Health Organization (WHO). The protozoan parasites also cause health problems in developed countries, e.g. Toxoplasma causes congenital toxoplasmosis and infections in immunosuppressed individuals. Membrane-bound pyrophosphatases (mPPases), which have no human homologs, are essential in parasites. It was recently shown that mPPases present in protozoan parasites have a unique molecular structure.1 They are thus ideal drug targets.
At present, there are no pharmacologically relevant inhibitors for mPPases.2 Here, our recently identified hit compounds will be presented for the first time. We decided to optimize one of the four mPPase hit compounds to improve the binding activities and to enhance the drug-like properties. Furthermore, in-house compounds yielded three more compound classes that showed inhibition of mPPase. To date, we have developed novel compounds showing IC50 values between 1 and 10 µM. These inhibitors have been subsequently screened against Plasmodium and Leishmania species, and preliminary results show that the best compounds inhibited Plasmodium falciparum with IC50 values of 7-19 µM, and Leishmania donovani with GI50 values of 0.6-22 µM. Furthermore, cytotoxicity studies showed that these compounds are well tolerated. These compounds will be further improved with medicinal chemistry tools into viable lead compounds showing favorable drug-like properties. Subsequently, the inhibitors will be validated in in vivo animal models. Therefore, the ultimate goal of this ground-breaking project will be novel drug-like inhibitors of pathogenic protozoan parasites.

1. Kellosalo, J., Kajander, T., Kogan, K. et al. Science, 337, 473–476 (2012).
2. Shah, N., Vidilaseris, K., Xhaard, H. et al. AIMS Biophysics 3, 171-194 (2016).