SO 3 H‐Carbon Catalyzed One‐Pot Multicomponent Synthesis of a Novel Series of 1,4‐Dihydro‐5 H ‐indeno‐[1,2‐ b ]‐pyridin‐5‐one Derivatives and Their Biological Evaluation

Abstract

The development of sustainable catalytic methods for synthesizing biologically relevant fused heterocycles remains an important challenge in organic and medicinal chemistry. This study reports a one‐pot multicomponent synthesis of indeno[1,2‐ b ]pyridin‐5‐one derivatives using glycerol‐derived SO 3 H‐carbon as a solid acid catalyst. The three‐component reaction of 1,3‐indanedione ( 1 ), aromatic aldehydes ( 2a–b ), and β ‐enaminones ( 3a–h and 3k–t ) was performed in water at 110°C using 20 wt% catalyst, affording 20 1,4‐DHIP derivatives ( 4a–t ) in 75%–88% yields. The synthesized compounds were evaluated for anticancer, antibacterial, and antifungal activities. Eleven compounds showing >50% inhibition against at least one cancer cell line at 10 µM were further assessed for IC 50 values against HepG2, DU‐145, MDA‐MB‐231, and SK‐OV‐3 cells. Compound 4j showed the highest potency against HepG2 cells (IC 50 = 3.42 µM), while 4o was most active against DU‐145 cells (IC 50 = 4.42 µM). Compound 4s exhibited the broadest antiproliferative activity, with IC 50 values of 3.68–9.52 µM and a selectivity index of 11.33 against HepG2 cells. Antimicrobial studies showed limited antibacterial and relatively weak antifungal activity. Overall, the SO3H‐carbon‐catalysed method provides a sustainable aqueous route to 1,4‐DHIP derivatives and identifies 4j, 4o, and 4s for further structural optimization and mechanistic investigation.