Biologically active triterpenoid derivatives I

Introduction: 
Triterpenoids are naturally occurring substances showing a large range of biological activities, including strong cytotoxic activity. This would make them suitable for use as pharmaceuticals.
Technology description: 
The present invention relates to the use of a compound of formula (I), or a pharmaceutically acceptable salt, crystal form, complex, hydrate, or hydrolysable ester thereof, in the preparation of a medicament for treating a patient suffering from leukemia, cancer or other proliferative disorder. A further embodiment relates to the use a compound of formula (I) in an assay for detecting the phosphorylation state of cellular substrates. The present invention also relates to novel compounds of formula (I), and the chemical synthesis thereof.
Development status: 
Laboratory scale, data on cell lines, limited ADME/Tox data, in vivo pharmacology and pharmacodynamics.
Advantages: 
The invention provides a novel class of compounds possessing a cytotoxic activity to a wide range of tumor cell lines. Our recent data demonstrate that selected compounds covered by these patents are hedge-hog inhibitors, pro-apoptotic compounds inducing selective release of cytochrome c from tumor cells, tubulin polymerization inhibitors, hemoxygenase I inducers, HIV maturation inhibitors, etc. These compounds will be useful as medicaments for the treatment of cancer and other diseases connected with abnormal proliferation and/or HIV infection.
Commercial offer: 
Exclusive/non-exclusive license to the know-how and data
Papers: 
Kvasnica, M., M. Urban, N. J. Dickinson, J. Sarek. Pentacyclic triterpenoids with nitrogen- and sulfur-containing heterocycles: synthesis and medicinal significance. Natural Product Reports. 2015, 20(32), 1303-1330. ISSN 0265-0568. IF: 10.986. PMID: 26030604 Borkova, L., L. Jasilkova, J. Rehulka, K. Frisonsova, M. Urban, I. Frydrych, I. Popa, M. Hajduch, N. J. Dickinson, M. Vlk, P. Dzubak, J. Sarek. Synthesis of cytotoxic 2,2-difluoroderivatives of dihydrobetulinic acid and allobetulin and study of their impact on cancer cells. European Journal of Medicinal Chemistry. 2015, 96(-), 482-490. ISSN 0223-5234. IF: 3.902. PMID: 25942059 Urban, M., M. Vlk, P. Dzubak, M. Hajduch, J. Sarek. Cytotoxic heterocyclic triterpenoids derived from betulin and betulinic acid. Bioorganic & Medicinal Chemistry. 2012, 20(11), 3666-3674. ISSN 0968-0896. IF: 2.903. PMID: 22551630 Urban, M., J. Sarek, M. Kvasnica, I. Tislerova, M. Hajduch. Triterpenoid Pyrazines and Benzopyrazines with Cytotoxic Activity. Journal of Natural products. 2007, 70(4), 526-532. ISSN 0163-3864. IF: 2.418. PMID: 17371067 Urban, M., J. Klinot, I. Tislerova, D. Biedermann, M. Hajduch, I. Cisarova. Reactions of activated lupane oxo-compounds with diazomethane: An approach to new derivatives of cytotoxic triterpenes. Synthesis-Stuttgart. 2006, 23, 3979-3986. ISSN 0039-7881. IF: 2.401. Sarek, J., M. Kvasnica, M. Urban, J. Klinot, M. Hajduch. Correlation of cytotoxic activity of betulinines and their hydroxy analogues. Bioorganic & Medicinal Chemistry Letters. 2005, 15(19), 4196-4200. ISSN 0960-894X. IF: 2.333. PMID: 16051489 Urban, M., J. Sarek, J. Klinot, G. Korinkova, M. Hajduch. Synthesis of A-seco derivatives of betulinic acid with cytotoxic activity. Journal of Natural Products. 2004, 67(7), 1100-1105. ISSN 0163-3864. IF: 1.849. PMID: 15270560 Urban, M., J. Sarek, I. Tislerova, P. Dzubak, M. Hajduch. Influence of esterification and modification of A-ring in a group of lupane acids on their cytotoxicity. Bioorganic & Medicinal Chemistry. 2005, 13(19), 5527-5535. ISSN 0968-0896. IF: 2.018. PMID: 16087342 Sarek, J., P. Dzubak, E. Klinotova, V. Noskova, V. Krecek, G. Korinkova, J. O. Thomson, A. Janostakova, S. Wang, S. Parsons, P.M. Fischer, N. Zhelev, M. Hajduch. New lupane derived compounds with Pro-Apoptotic activity in cancer cells: Synthesis and structure-activity relationships. Journal of Medicinal Chemistry. 2003, 46(25), 5402-5415. ISSN 0022-2623. IF: 4.566. PMID: 14640549
Technology/IP owners: 
Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc Charles University, Prague Cyclacel Ltd.
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)