Synthesis and charachterisation of new urea derivatives of chloroquine and aminoalcohols

Klorokin je antimalarijski lijek za kojeg je poznato da ima i antitumorsko djelovanje. U ovom radu dan je pregled literaturnih podataka o antitumorskom djelovanju antimalarika, s naglaskom na klorokinu, kao i o njihovom potencijalu da posluže kao spojevi uzori za sintezu novih antitumorskih lijekova. Detaljnije je opisan proces autofagije, budući da se smatra da je glavni mehanizam kojim klorokin inhibira preživljavanje stanica raka vezan uz inhibiciju autofagije. U svrhu daljnjeg istraživanja potencijalne antitumorske aktivnosti derivata klorokina sintetizirano je 5 novih spojeva: BtcCQ (3) i uree 4a-d. Novosintetizirani spojevi su okarakterizirani uobičajenim analitičkim tehnikama (IR, MS, 1H i 13C NMR). Spojevi 3 i 4a-d u potpunosti odgovaraju Lipinskijevim, Gelovanijevim i Veberovim pravilima, odnosno kriterijima alata Bioavailability radar (SwissAdme). U daljnjim istraživanjima, koja prelaze okvire ovoga diplomskog rada, bit će ispitano njihovo citostatsko djelovanje.Chloroquine is an antimalarial drug with well-known cytostatic properties. This thesis gives an overview of the current literature regarding the cytotoxic activity of antimalarials and their potential to serve as lead compounds for the synthesis of new anticancer agents. The process of autophagy is described in more detail since it is believed that chloroquine owes its anticancer activity to the inhibition of autophagy. Five novel chloroquine derivatives were synthesized: BtcCQ (3) and ureas 4a-d. Newly synthesized compounds were characterized by standard analytical techniques (IR, MS, 1H and 13C NMR). Compounds 3 and 4a-d comply with Lipinski, Gelovani and Veber rules, as well as with the criteria of Bioavailability radar (SwissAdme). Future investigations will focus on the evaluation of their cytostatic activity