Synthesis and in vitro cytotoxic evaluation of some novel hexahydroquinoline derivatives containing benzofuran moiety

摘要

A series of new ethyl 4-(2-(benzofuran-2-yl)-4-substituted-1,4,5,6,7,8-hexahydroquinolin-1-yl)-benzoate 3a-c was synthesized by Michael condensation of benzofuran chalcones 1a-c and cyclohexanone to give 2-(2-benzofuranyl)-4-substituted-5,6,7,8-tetrahydro-4-H -chromene 2a-c, followed by reaction of the latter with ethyl 4-aminobenzoate. Condensation of 3a-c with different amines afforded the corresponding amides 4a-e. On the other hand, upon treatment compounds 3a-c with hydrazine hydrate gave the benzohydrazide derivatives 5a-c. The reaction of compounds 5a-c with different thio/isocyanate gave the corresponding thiosemicarbazide and semicarbazide derivatives 6a-c. Meanwhile compounds 5a-c were reacted with ethyl cyanoacetate and different beta-dicarbonyl compounds such as acetyl acetone, ethyl acetoacetate, and diethyl malonate to afford pyrazolyl derivatives 7a, b; 8a, b; 9a, b; and 10a-c, respectively. Moreover, 5a-c were reacted with carbon disulfide to synthesize the corresponding oxadiazolyl derivatives 11a-c, while their condensation with different aromatic aldehydes gave the corresponding Schiff bases 12a-d. Cytotoxic evaluation of some of the newly synthesized compounds against human hepatocellular carcinoma cell lines (HepG-2) revealed that the tested compounds produce promising inhibitory effect against the growth of HepG-2 cells with IC50 values ranged from 11.9 to 19.3 A mu g/mL.