engleski

Synthesis of urea-type harmiprims - novel harmine-primaquine hybrids

Many antimalarial agents possess anticancer activity: hydroxychloroquine, chloroquine, and other antimalarial drugs were evaluated or are currently under evaluation in numerous clinical trials against different cancer types. For more than a decade, our research group has been focused on the hybridization of the well-known antimalarial drug primaquine (PQ) in the search for potential anticancer agents. This resulted in several compounds displaying high activity against several cancer cell lines or high selectivity towards MCF-7 cells [1]. As a continuation of our work, we have prepared a series of urea-type PQ hybrids bearing harmine moiety – harmiprims. Harmine is a naturally occurring β-carboline alkaloid with pronounced antitumor activity through diverse mechanisms [2]. The scheme outlines the general route leading to the title compounds (Figure). Benzotriazolide 1 was synthesized by acylation of PQ with 1-benzotriazole carboxylic acid chloride [3], while the preparation of harmine-based amines 2-6 at positions C-1, C-3, O-6, O-7, and N-9 of the β-carboline core was previously described by us [4]. Microwave-assisted synthesis was utilized in the preparation of the title compounds 7-11 from benzotriazolide 1 and a corresponding harmine-based amine. The structures of newly prepared compounds 7-11 were confirmed by standard methods (IR, 1H, 13C NMR, MS). Evaluation of their antiproliferative activity is in progress.

harmine ; primaquine ; urea ; benzotriazole

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