Alkaloid-Based Isoxazolylureas: Synthesis and Effect in Combination with Anticancer Drugs on C6 Rat Glioma Model Cells
Gulim K. Mukusheva,
Roza I. Jalmakhanbetova,
Altynay Zh. Shaibek,
Manshuk S. Nurmaganbetova,
Aigerym R. Zhasymbekova,
Oralgazy A. Nurkenov,
Ekaterina A. Akishina,
Irina A. Kolesnik,
Evgenij A. Dikusar,
Tatiana I. Terpinskaya,
Vladimir A. Kulchitsky,
Vladimir I. Potkin,
Alexander L. Pushkarchuk,
Dmitry A. Lyakhov,
Dominik L. Michels
Affiliations
Gulim K. Mukusheva
Faculty of Chemistry, Karaganda Buketov University, Karaganda 100024, Kazakhstan
Roza I. Jalmakhanbetova
Faculty of Natural Sciences, L.N. Gumilyov Eurasian National University, Astana 010000, Kazakhstan
Altynay Zh. Shaibek
Faculty of Chemistry, Karaganda Buketov University, Karaganda 100024, Kazakhstan
Manshuk S. Nurmaganbetova
Faculty of Chemistry, Karaganda Buketov University, Karaganda 100024, Kazakhstan
Aigerym R. Zhasymbekova
Faculty of Chemistry, Karaganda Buketov University, Karaganda 100024, Kazakhstan
Oralgazy A. Nurkenov
Institute of Organic Synthesis and Coal Chemistry of the Republic of Kazakhstan, Karaganda 100008, Kazakhstan
Ekaterina A. Akishina
Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus, 220072 Minsk, Belarus
Irina A. Kolesnik
Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus, 220072 Minsk, Belarus
Evgenij A. Dikusar
Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus, 220072 Minsk, Belarus
Tatiana I. Terpinskaya
Institute of Physiology, National Academy of Sciences of Belarus, 220072 Minsk, Belarus
Vladimir A. Kulchitsky
Institute of Physiology, National Academy of Sciences of Belarus, 220072 Minsk, Belarus
Vladimir I. Potkin
Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus, 220072 Minsk, Belarus
Alexander L. Pushkarchuk
Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus, 220072 Minsk, Belarus
Dmitry A. Lyakhov
Computer, Electrical and Mathematical Science and Engineering Division, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia
Dominik L. Michels
Computer, Electrical and Mathematical Science and Engineering Division, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia
Alkaloid-based urea derivatives were produced with high yield through the reaction of anabasine and cytisine with isoxazolylphenylcarbamates in boiling benzene. Their antitumor activity, in combination with the commonly used five anticancer drugs, namely cyclophosphane, fluorouracil, etoposide, cisplatin, ribomustine with different mechanisms of action, was investigated. Based on the quantum chemical calculations data and molecular docking, hypotheses have been put forward to explain their mutual influence when affecting C6 rat glioma model cells.
