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

Abstract

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 b-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 IC 50 values ranged from 11.9 to 19.3 lg/mL.

Novel Pyridothienopyrimidine Derivatives: Design, Synthesis and Biological Evaluation as Antimicrobial and Anticancer Agents

“…Heterocyclic ring systems are considered key molecular structures in medicinal chemistry. In addition to their presence in the skeleton of many biological molecules such as hemoglobin, DNA, RNA, vitamins, hormones, and heterocyclic compounds [ 12 , 13 , 14 ], they produce a wide range of biological activities [ 15 , 16 ]. Accordingly, the structural diversity and biological prominence of heterocyclic compounds have made them attractive synthetic targets in drug design and discovery for many years [ 12 , 13 ].…”