Anti-tumor triterpenoids substituted with nitrogen substituents

Introduction: 
Triterpenoids are natural compounds with a number of biological activities including anticancer. Most of the triterpenoids are not sufficiently water soluble, which makes the biological tests difficult and also is a reason for low bioavailability. Therefore it is important to improve the solubility by modifying the compounds with polar functional groups such as quarternary ammonium salts.
Technology description: 
The invention is based on the introduction of quarternaty ammonium salts into the triterpenic structure of active compounds. Those ammonium salts are connected to the 18-carboxylic acid via alkylester linker. Compounds containing both aliphatic and aromatic quarternary ammonium salts were studied and patented and they showed high in vitro cytotoxic activities.
Development status: 
Laboratory scale, data on cell lines, primarily human tumors, orientational pharmacology/toxicology on rodents.
Advantages: 
The invention provides a large group of novel compounds active on broad spectrum of cancer cell lines. New anti-cancer pharmaceuticals can be based on the invention as well as abnormal proliferation therapeutics.
Commercial offer: 
Exclusive/non-exclusive licence to the patent, related know-how and data
Papers: 
Kvasnica, M., Urban, M., Dickinson, N. J., Sarek, J. Pentacyclic triterpenoids with nitrogen- and sulfur-containing heterocycles: synthesis and medicinal significance. Nat Prod Rep. 2015 Jun 1. PubMed PMID: 26030604 Borkova, L., Jasikova, L., Rehulka, J., Frisonsova, K., Urban, M., Frydrych, I., Popa, I., Hajduch, M., Dickinson, N. J., Vlk, M., Dzubak, P., Sarek, J. Synthesis of cytotoxic 2,2-difluoroderivatives of dihydrobetulinic acid and allobetulin and study of their impact on cancer cells. Eur J Med Chem. 2015 May 26, doi: 10.1016/j.ejmech.2015.03.068. Epub 2015 Apr 1. PubMed PMID: 25942059. Biedermann, D., Eignerova, B., Hajduch, M., Sarek, J. Synthesis and Evaluation of Biological Activity of the Quaternary Ammonium Salts of Lupane-, Oleanane-, and Ursane-Type Acids. Synthesis – Stuttgart 2010, 22, 3839
IP protection: 
CZ 301158
Technology/IP owners: 
Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc
Contact: 
More information is available upon signing a CDA/NDA. Please contact IMTM´s director (director@imtm.upol.cz) or the technology transfer office (tto@imtm.upol.cz).