Synthesis, cytotoxic, anti-lipoxygenase and anti-acetylcholinesterase capacities of novel derivatives from harmine

We synthesized two series of new hydrazide harmine derivatives. The reaction of harmine 1 with ethyl acetate chloride afforded the corresponding ethyl ester 2. The treatment of 2 with hydrazine hydrate gave the hydrazide 3 which further converted into hydrazones 4a–j and dihydrazides 5a–c. A series of new triazoles 7a–f has also been prepared from the suitable propargyl harmine 6. The synthesized derivatives were characterized by ¹H-NMR, ¹³C-NMR, and HRMS and evaluated for their activities against MCF7, HCT116 OVCAR-3, acetylcholinesterase and 5-lipoxygenase. The most hydrazones derivatives 4a-j have a good cytotoxic activity against all cell lines, when 4a, 4d, 4f and 4 g are more active than 1 (against OVCAR-3 IC₅₀ 16.7–2.5 μM). The compound 6 was the most active (IC₅₀=1.9 μM) against acetylcholinesterase. Some compounds exhibited significant activity against 5-lipoxygenase (IC₅₀=30.9–63.1 μM).