Journal of Chemistry and Biochemistry

Synthesis, Characterization and Anticancer Activity of Novel 1, 3, 4- Oxadiazolyl- and Pyrazolylquinoxalines
Omaima O. M. Farahat, Kamal F. M. Atta

Abstract
Synthesis of 2-[3-(5-hydroxymethyl)-1-phenyl-1H-pyrazol-3-yl]-2-oxoquinoxalin-1-yl acetohydrazide (3) was accomplished by the reaction of 3-(5-acetoxymethyl-1- phenyl-1H-pyrazol-3-yl)-1,2-dihydroquinoxalin-2-one (1) with ethyl bromoacetate followed by treatment with hydrazine hydrate under reflux. The key starting material 3 was used for the preparation of the target oxadiazolylpyrazolyl- and dipyrazolylquinoxalines. Thus, the reaction of 3 with ethyl formate or acetic acid afforded the acyl carbohydrazide derivatives 4 and 5 respectively. Moreover, benzoylation of 3 with benzoyl chloride in pyridine yielded the N-,O-dibenzoyl derivative 6 which, upon boiling with acetic anhydride or dimethyl formamide gave the O-benzoyl derivative 11. Furthermore, treatment of 3 with formic acid or acetic acid in the presence of phosphoryl chloride yielded the respective oxadiazolylpyrazolylquinoxalines 9 or 10. O-Acetylation of 4 and 9 or 3, 5 and 8 give the corresponding 1,3,4-oxadiazolylpyrazolyl quinoxalines 7 or 8. Additionally, synthesis of [3-(5-hydroxymethyl)-1-phenyl-1H-pyrazol-3-yl]-1-[(5-mercapto-1,3,4- oxadiazol-2-yl)methyl]quinoxalin-2-one (12) was performed by refluxing the carbhydrazide 3 with carbon disulphide which upon acetylation afforded the O-,Sdiacetyl derivative 13. On the other hand, the dipyrazolylquinoxalines 14 and 16 were obtained upon heterocyclization of the hydrazide 3 with acetylacetone or ethyl acetoacetate respectively. Acetylation of 14 and 16 gave the monoacetyl derivatives 15 and 17, respectively. The structural investigation of the new compounds is based on chemical and spectroscopic evidences. Anti-tumor evaluation of the synthesized compounds in vitro against three cell lines HCT-116 (colon carcinoma), HEPG2 (liver carcinoma) and MCF-7 (breast carcinoma) revealed that they possess high anti-tumor activities.

Full Text: PDF     DOI: 10.15640/jcb.v2n2a7