engleski

Novel cinnamic acid-primaquine conjugates of semicarbazide type

Molecular hybridization approach based on the combination of pharmacophoric moieties of different compounds was used to produce new hybrid molecules with cinnamic acid derivatives (CAD) and primaquine (PQ) motifs bind via spacer. CAD, a large group of compounds appearing naturally in plants, have a long history of human use. Impressive number of papers report on their biological activities (antitumor, antimicrobial, antioxidative, antidiabetic, hepatoprotective, hypolipemic, antimalarial) and low toxicity (1-3). On the other hand, primaquine is a well-known antimalarial drug with antiproliferative potential. In our recent work we have shown that primaquine derivatives with substituted terminal amino group possess significant cytostatic activity in low micromolar concentrations towards various cancer cell lines (4, 5) or high selectivity towards MCF- 7(breast cancer). The starting compound benzotriazole carboxylic acid chloride 1 was used for the preparation of primaquine benzotriazolide 2, which reacted with hydrazine hydrate and gave semicarbazide 3. The title CAD-primaquine conjugates 5a-k were prepared by acylation of product 3 with corresponding CAD chlorides 4a-k. The following CAD were used: cinnamic acid, -methylcinnamic acid, methoxy, dimethoxy, trimethoxy, methylenedioxy, chloro, fluoro, trifluoromethyl and bistrifluoromethyl cinnamic acid. Structures of newly prepared N- cinnamoyl-primaquine conjugates were confirmed by IR, 1H and 13C NMR and MS spectroscopy. Evaluation of their biological activity is in progress.

primaquine ; cinnamic-acid derivative ; conjugate ; synthesis

Poster je izlagan i na 6. simpoziju studenata farmacije i medicinske biokemije FARMEBS 2017, Zagreb, 27.5.2017.