Synthesis, antitumor activity, and electrochemical behavior of some piperazinyl amidrazones

Abstract

New piperazinyl amidrazones have been synthesized by direct interaction of the corresponding aryl hydrazones with the appropriate piperazine. On the basis of preliminary screening data for these new compounds, the antitumor activity of 1-(4-methylpiperazin-1-yl)-1,2-propandione 1-[2-(4-chlorophenyl)hydrazone] and 1-(4-ethylpiperazin-1-yl)-1,2-propandione 1-[2-(4-chlorophenyl)hydrazone] was evaluated. Mean 50% growth inhibition (GI ₅₀), 50% cell killing (LC ₅₀), and total growth inhibition (TGI) for both compounds were calculated on the basis of data obtained from 55 test cell lines. Mean GI ₅₀ is significantly lower for the methylpiperazine derivative (4.81 μM) compared with that of the ethylpiperazine derivative (4.92 μM) (p > 0.01); however, mean TGI is not measurably different (p > 0.1) for both compounds (4.52 and 4.52 μM, respectively). Both compounds exhibit substantial antitumor activity against a number of cell lines at 4 μM concentration. It was found that the methylpiperazine derivative is more potent against leukemia cell lines (mean GI ₅₀ = 4.73 μM and mean TGI = 4.36 μM), whereas the ethylpiperazine derivative is more potent against CNS cell lines (GI ₅₀ = 4.68 μM and mean TGI = 4.37 μM). Cancers of the breast are least susceptible to methylpiperazine derivative activity compared with all other cell lines (mean GI ₅₀ = 4.91 μM). Melanomas and renal cancers are least susceptible to the ethylpiperazine derivative activity as compared with other cancer types (mean GI ₅₀ = 5.06 μM). Cyclic voltammetry has been employed to probe the electrochemical oxidation and reduction of the piperazinyl amidrazones at glassy carbon electrodes in dimethylformamide containing tetramethylammonium tetrafluoroborate.

Graphical abstract