Ligand-free MCR for linking quinoxaline framework with a benzimidazole nucleus: a new strategy for the identification of novel hybrid molecules as potential inducers of apoptosis

Abstract

We report a true MCR involving the reaction of N-(prop-2-ynyl)quinoxalin-2-amine derivatives with 2-iodoanilines and tosyl azide in the presence of 10 mol% of CuI and Et3N in DMSO to afford the pre-designed hybrid molecules containing quinoxaline framework linked with a benzimidazole nucleus. The MCR proceeds in the absence of any ligand and/or lateral addition of the catalyst/base affording products within 30 min in good yields, some of which showed encouraging apoptosis inducing properties in zebrafish.

Small hybrid heteroaromatics: resourceful biological tools in cancer research

“…The anticancer activity studies revealed that these compounds induced signicant apoptosis in zebrash embryos. 29 In another study, green chemistry was applied to link the three pharmacophoric groups (quinoline, triazole, and dihydroquinoline) to form a novel series of hybrid molecules. The process involved one-pot sequential azidation and coppercatalyzed azide-alkyne cycloaddition (CuAAC) in water under mild conditions.…”

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

“…The multicomponent strategy has provided an easy access to the synthesis of complex bioactive molecules with multiple point diversity incorporating up to eight components in one-pot [8]. The pharmaceutical industry has witnessed a considerable surge in drug synthesis via multicomponent strategies [9][10][11], including the synthesis of atorvastatin, a potent HMG-CoA reductase inhibitor. Dömling and co-workers efficiently demonstrated an Ugi-based MCR approach towards the synthesis of atorvastatin in four steps ruling out the lengthy seven step protocol, and paving a rapid entry to the drug discovery market [12].…”

Synthesis, anticancer evaluation and molecular docking studies of new benzimidazole- 1,3,4-oxadiazole derivatives as human topoisomerase types I poison

“…These drugs are known to hinder the breakage/reunion reaction of topoisomerase I, in which the enzyme is reversibly trapped in a state where the DNA is cleave 6 . Furthermore, benzimidazole is known to be a versatile scaffold that possess potential anticancer, antitumor and antiproliferative activities [21][22][23][24][25][26][27] . Similarly, oxadiazole has engrossed significant attention of medicinal chemists owing to their wide range of useful pharmacological actions particularly cytotoxic activities against DNA topoisomerase I [28][29][30][31] .…”