Urea and carbamate derivatives of primaquine: Synthesis, cytostatic and antioxidant activities

We describe novel urea and carbamate derivatives of primaquine, and their cytostatic and antioxidant activities. 1-(5-Hydroxypentyl)-3-[4-(6-methoxy-quinolin-8-ylamino)-pentyl]-urea ( 3c) shows extreme selectivity toward SW 620 colon cancer cells. The novel urea primaquine derivatives 3 were prepared by aminolysis of primaquine benzotriazolide 2 with several hydroxyamines and ethylendiamine, while carbamates 4 were synthesized from the same precursor 2 and alcohols. All compounds are fully chemically characterized and evaluated for their cytostatic and antioxidant activities. The most prominent antiproliferative activity was obtained by compounds 3c, 3d, 3g, and 5b (IC 50 = 9–40 μM). 1-(5-Hydroxypentyl)-3-[4-(6-methoxy-quinolin-8-ylamino)-pentyl]urea ( 3c) showed extreme selectivity toward SW 620 colon cancer cells (IC 50 = 0.2 μM) and a bit less toward lung cancer cells H 460. Hydroxyurea 3h showed the highest interaction with DPPH. Primaquine twin drug 3g showed very significant inhibition on LOX soybean (IC 50 = 62 μM). Almost all the tested derivatives highly inhibited lipid peroxidation, significantly stronger than primaquine phosphate.