Synthesis, Biological Activities and Molecular Docking analysis of a Novel Series of 11H-Indeno[1,2-b]quinoxalin-11-one Derivatives

Abstract

In this study, olefin adducts were synthesized from Wittig reactions on carbonyl group and stereo-identity of the alkene products. The reaction of 11H-Indeno[1,2-b]quinoxalin-11-one with few stabilized phosphonium ylides yielded a combination of the corresponding E and Z olefins in each case. On the other hand, the reaction of 11H-indeno[1,2-b]quinoxalin-11-one with dialkyl phosphites gave related phosphonates. The aldol condensation reaction of 11H-Indeno[1,2-b]quinoxalin-11-one with boiling dry acetone and/or 2-butanone in presence of aluminum oxide or anhydrous potassium carbonate as a catalyst led to the formation of the β-hydroxy ketones. The nucleophilic addition reaction of acetone and/or 2- butanone to (E)-alkyl 2-(11H-indeno[1,2-b]quinoxalin-11-ylidene)acetate in presence of aluminum oxide or anhydrous potassium carbonate as a catalyst led to the formation of the corresponding an addition products.Reaction mechanisms are taken into consideration and the structural assignments of the new compounds are based on the chemical and spectroscopic evidences. The cytotoxic activity of some new compounds had been evaluated against human hepatocellular carcinoma cell line (HePG2) and human Caucasian breast adenocarcinoma (MCF7). Compounds 6b,c showed higher cytotoxicity towards breast (MCF7) most cancers cellular line than the reference drug (Doxorubicin). The binding mode of phosphonates 6 changed into similarly tested by using molecular docking studies