Neat multicomponent assembly of highly functionalized Acenaphtho[1,2‐b]pyrroles, in vitro evaluation for antioxidant and cytotoxic activities

A facile one-pot multicomponent route for the synthesis of acenaphtho[1,2-b] pyrroles from acenaphthenequinone using amines and activated alkynes is reported. The method involves the formation of a zwitterionic intermediate through Huisgen dipolar cycloaddition reaction of amines and activated alkynes. The solvent free method was found to be superior than conventional methods in terms of reaction resulted in excellent yields in the presence of electron releasing and halogen containing substituents on the primary aromatic amine and on altering the alkyl substituents of the acetylenic ester. Antioxidant activity of the titled derivatives (4a-j) was investigated by the Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging method. Compounds 4b and 4j showed relative radical scavenging potential comparable to that of ascorbic acid (IC50 = 25.20 mu g/mL). Cell growth inhibition testing was carried out using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay in two different human cancer cell lines colon (HT- 29) and breast (MCF-7). Compound 4j is comparatively effective against HT-29 cells (GI50 = 23.6 +/- 0.11) in comparison with standard 5-FU (GI50 = 25.5 +/- 0.29) and also moderately effective against MCF-7 cells (GI50 = 10.3 +/- 0.12) in comparison with standard Doxorubicin (GI50 = 2.6 +/- 0.06) among the other evaluated derivatives. The results revealed the promising lead compounds 4j for further optimization toward the discovery and development of new anti-cancer agents.