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

## TL;DR

A new coumarin compound was synthesized and shown to have strong anti-cancer, antimicrobial, and antioxidant effects, with detailed molecular interactions studied.

## Contribution

A novel coumarin derivative was synthesized and comprehensively evaluated for multiple bioactivities with molecular docking and dynamics simulations.

## Key findings

- Compound 2d showed strong cytotoxicity against MCF-7 breast cancer cells.
- Compound 2i exhibited the strongest antioxidant activity comparable to Trolox.
- Molecular docking and dynamics simulations confirmed stable interactions of compound 2d with the 1T8I enzyme.

## Abstract

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 (IC50 = 2.54 ± 0.12 µM), surpassing camptothecin. Compound (2b) showed strong activity against HeLa cervical cancer cells (IC50 = 5.23 ± 0.12 µM), while compound (2a) demonstrated notable effects on HepG2 liver cancer cells (IC50 = 8.57 ± 0.42 µM). All three compounds displayed low toxicity toward normal LLCPK1 kidney cells, with IC50 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 (SC50 = 7.36 ± 0.18 µM), comparable to Trolox (SC50 = 6.12 ± 0.15 µM). Molecular docking indicated that compound (2d) (pose 232) binds tightly to the 1T8I enzyme (ΔG = –9.92 kcal mol−1, Ki = 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.