Synthesis of a novel coumarin via the Mannich reaction: in vitro and in silico evaluation of anti-cancer, antimicrobial and antioxidant activities

The novel coumarin derivatives ( 2a – 2j ) were synthesized via the Mannich reaction and evaluated for anti-cancer, antimicrobial and antioxidant activities. Compound ( 2d ) exhibited the most potent cytotoxicity against MCF-7 breast cancer cells (IC 50 = 2.54 ± 0.12 µM), surpassing camptothecin. Compound ( 2b ) showed strong activity against HeLa cervical cancer cells (IC 50 = 5.23 ± 0.12 µM), while compound ( 2a ) demonstrated notable effects on HepG2 liver cancer cells (IC 50 = 8.57 ± 0.42 µM). All three compounds displayed low toxicity toward normal LLCPK1 kidney cells, with IC 50 values exceeding 94 µM. Antimicrobial assays revealed that compounds ( 2a ) and ( 2f ) effectively inhibited Bacillus subtilis , with minimum inhibitory concentration values of 25 and 75 µM, respectively. Compound ( 2i ) showed the strongest antioxidant effect (SC 50 = 7.36 ± 0.18 µM), comparable to Trolox (SC 50 = 6.12 ± 0.15 µM). Molecular docking indicated that compound ( 2d ) (pose 232) binds tightly to the 1T8I enzyme (Δ G = –9.92 kcal mol −1 , K i = 0.01 µM), forming key interactions with Arg 488 and Lys 532. Molecular dynamics simulations confirmed the complex’s stability in aqueous solution over 90 ns.