Synthesis, DFT studies, and cytotoxicity against (HepG-2) of some hetero furan-hydrazide derivatives

Abstract

Herein, the building block synthon cyano-(furan-2-ylmethylene)-acetohydrazide (3) was synthesized and utilized for constructing a wide variety of nitrogen heterocyclic compounds. Cyclization of acetohydrazide 3 in boiling EtOH and 0.5 ml piperidine afforded 2-cyano-(furan-2-ylmethylene)-3-phenylacrylohydrazide (5). Also, a new series of a new chromen-2-imine derivatives 8a-d have been synthesized via stirring starting moiety 3 with 2-hydroxy-5-(phenyldiazenyl)benzaldehyde derivatives 6a-d under heating at 50 °C in the presence of piperidine as a catalyst. Moreover, coupling of active methylene 3 with arylamine diazonium salts 10 a-h formed the corresponding 2-(2-furan-2-ylmethylene)hydrazineyl)-N-(4-substitutedphenyl)-2-oxoaceto-hydrazonoyl cyanide derivatives 11a-h in overall good yields. Furthermore, creating molecules with pyrazole rings was prepared by coupling acetohydrazide 3 with heterocyclic amine diazonium salts 14–16. The structural elucidation was achieved for the target molecules by different spectral parameters such as FTIR, 1H NMR, and 13C NMR spectra. Molecular modeling studies displayed the geometrical structures for the investigated compounds by using the geometrical studies (DFT) of the synthesized molecules that were investigated by the initio/3021 G quantum mechanical method. The in vitro cytotoxic activity of new furan-hydrazide derivatives against the HepG-2 cell line was evaluated using the reference doxorubicin. Compounds 8a and 8b exhibited high reactivity against the HepG-2 cell line, with IC-50 values of 9, and 8.1 μM, respectively. Cell cycle studies indicate that the most potent furan derivatives 8a and 8b arrested cells at the G2/M phase and induced apoptosis.