engleski

Synthesis and characterisation of novel primaquine ureas and semicarbazides

Primaquine (PQ), a member of the 8-aminoquinoline group, is a well known antimalarial drug with pronounced antitumour activity as well [1]. Recently, we have reported several papers describing the synthesis, antitumour and antioxidant activity of various primaquine derivatives. The majority of our previously synthesized primaquine semicarbazides showed either prominent cytostatic activity towards all the tested cell lines or high selectivity towards MCF-7 cells with IC50 values in the low micromolar range. Urea derivatives were generally less active than their semicarbazide analogues, but still selective towards MCF-7 cells [2-4]. Among the synthesized compounds, primaquine semicarbazides and ureas with halogenated phenyl moieties showed significant cytostatic activity [4]. Based on these findings, we found it worth to prepare urea and semicarbazide primaquine derivatives bearing various phenyl moieties with electronegative substituents (halogens or oxygen) at the one and primaquine moiety at the other end. Scheme outlines the general preparative route. The starting compound benzotriazole carboxylic acid chloride (1) was used for the preparation of both active ureas (2a-j) and benzotriazolide (4). Compounds 3a-j and 6a-j were obtained in the reaction of primaquine or primaquine semicarbazide (5) and corresponding active ureas (2a-j). Compound 4 with hydrazine hydrate gave primaquine semicarbazide (5). Structures of newly prepared primaquine derivatives were confirmed by IR, 1H and 13C NMR spectroscopy and MS. Evaluation of their biological activity is in progress.

primaquine; synthesis; urea; semicarbazide

nije evidentirano