Synthesis, and Antitumor Activity of Some N1-(Coumarin-7-yl) Amidrazones and Related Congeners

Abstract

A series of new N1-(coumarin-7-yl)amidrazones incorporating N-piperazines and related congeners were synthesized by reacting the hydrazonoyl chloride derived from 7-amino-4-methylcoumarin with the appropriate piperazines. The chemical structures of the newly prepared compounds were supported by elemental analyses, 1H-NMR, 13C-NMR, and ESI-HRMS spectral data. The antitumor activity of the newly synthesized compounds was evaluated. Among all the compounds tested, 7-{2-[1-(4-(1-benzyl-2-ethyl-4-nitro-1H-imidazol-5-yl)piperazin-1-yl)-2-oxopropylidene]hydrazinyl}-4-methyl-2H-chromen-2-one (3n) was the most potent against MCF-7 and K562 cells, with IC50 values of 20.2 and 9.3 μM, respectively.

Synthesis and Bioassay of Novel Substituted Pyrano[2,3‐f]cinnoline‐2‐ones

“…The N ‐(4‐methyl‐2‐oxo‐2H‐chromen‐7‐yl)‐2‐oxopropanehydrazonoyl chloride synthon ( 3 ), required in this study, was prepared via diazotization of 7‐amino‐4‐methylcoumarin, followed by coupling with 3‐chloro‐2,4‐pentanedione (Japp–Klingemann reaction) in basic medium (NaOAc or pyridine) (Scheme ). The resulting orange‐colored solid precipitate was collected, washed several times with water, dried, and recrystallized from acetonitrile.…”

“…The resulting orange‐colored solid precipitate was collected, washed several times with water, dried, and recrystallized from acetonitrile. The intermediate arenediazonium chloride solution was freshly prepared by diazotization of 7‐amino‐4‐methylcoumarin which, in turn, was prepared from m ‐aminophenol according to literature procedure . On the other hand, synthesis of the respective amidrazones 4a , 4b , 4c , 4d , 4e , 4f , 4g , 4h , 4i , 4j , 4k , 4l , 4m , was achieved in good yield, via interaction of hydrazonoyl chloride ( 3 ) in ethanol in the presence of triethylamine, with the appropriate secondary amines at 0°C.…”

“…Compounds 4a , 4b , 4c , 4d , 4e , 4f , 4g , 4h , 4i , 4j , 4k , 4l , 4m were synthesized according to the following general literature procedure . To a stirred cold suspension (0 to −10°C) of compound 3 (1.0 g, 3.6 m M ) in 20 mL of ethanol, a solution of the appropriate piperazine or secondary amine (2.0 m M ) and triethylamine (3 mL) in 10 mL of ethanol was added.…”

“…Coumarin derivatives have drawn considerable attention from researchers because of their role in natural and synthetic organic chemistry and their interesting biological activities. Compounds containing a coumarin nucleus exhibit various biological activities, such as anticoagulant and antithrombotic properties and also found numerous therapeutic applications in photochemo‐ , antitumor , and anti‐HIV therapy , while others have served as antibacterial , antifungal , anti‐inflammatory , antiviral (including HIV ), anticoagulant agents, antitubercular , and dyes . Interestingly, 7‐amino‐4‐methylcoumarin (AMC) is employed for labeling l ‐α‐amino acids (AA) via coupling of the respective AA‐carboxyl and AMC‐7‐amino functions ; these labeled α‐amino acids are utilized as synthetic fluorogenic and highly specific substrates for aminopeptidases, in which case hydrolysis of the amide bond results in liberation of the fluorescent.…”

“…In view of the interest in the activity spectrum and profile of cinnolines and coumarins, and in continuation of our work on the synthesis and bioassay of new compounds of pharmacological and biological interest , we describe herein the preparation and characterization of some novel 9‐substituted‐4,10‐dimethylpyrano[2,3‐ f ]cinnolin‐2‐ones along with their antitumor activities.…”