Synthesis and Theoretical Study of Novel Imidazo[4,5-b]pyrazine-Conjugated Benzamides as Potential Anticancer Agents

A green synthetic protocol has been developed for the synthesis of imidazo[4,5- b ]pyrazine-conjugated benzamides in 80–85% yield via one-pot three-component reaction of phthalic anhydride, substituted anilines, and pyrazine-2,3-diamine in the presence of phosphoric acid as catalyst in water at 95–100°C for 100–120 min. The proposed protocol has the advantages of mild reaction conditions, good yields, short reaction times, and environmental friendliness. The products have been isolated as clean compounds without using column chromatography. The synthesized imidazo[4,5- b ]pyrazine-conjugated benzamides were tested for their anticancer activity against liver and ovarian cancer cell lines (HepG2 and HeLa) with IC 50 values ranging from 9.8 to 100 µM. Molecular modeling studies revealed the crucial binding interactions of the target protein and the synthesized ligands. In addition, permeability and bioavailability properties have been predicted along with molecular descriptors such as shape index, molecular complexity, and molecular flexibility. The insights drawn from these studies, would help us to design better potent analogs in the future.