engleski

Synthesis of new carbamate-type harmicenes

Harmine is a naturally occurring β-carboline alkaloid that possesses a broad range of biological activities, including antitumor and antimalarial. We designed and prepared several series of hybrid compounds in which harmine was covalently linked to other biologically active compounds: cinnamic acid derivatives (CADs, harmicines), quinolines (harmiquins), coumarins (harmirins) and ferrocene (harmicens), with the aim of improving its biological activities and overcoming the growing resistance to malaria and cancer chemotherapy. The linker between the two moieties was either an amide bond or triazole ring. Our research showed that hybridization is a valuable strategy for obtaining compounds with enhanced activities. Encouraged by those results, we decided to prepare novel carbamate-type harmicines at the N-9 position of harmine’s β- carboline core. The targeted carbamates 4a-g were obtained by the reaction of amine 1 and cinnamyl alcohols 2a-g under mild reaction conditions. Cinnamyl alcohols 2a-g were prepared from the corresponding CADs, whereas amine 1 was prepared from harmine. To investigate the effect of substituents at the CADs benzene ring on harmicines biological activity, we chose seven CADs with different substitution pattern (o-Cl, m-Cl, m-OCF3, p-Br, p-CH3, p-CF3, p-NO2). Reactions which require anhydrous conditions were performed under argon atmosphere in anhydrous solvents. All reagents and solvents were purchased from commercial sources. The title compounds 4a-g were purified by column chromatography, triturated with diethyl ether and fully characterized by standard methods (IR, 1H- and 13C-NMR, and MS).

harmine, cinnamic acid derivatives, harmicines, resistance, carbamate-type

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