Two Novel Coumarin Compounds: Synthesis, in Vitro Antibacterial Anticancer, and in Silico Docking and Molecular Dynamics

Coumarin derivatives possess diverse biological activities, encompassing antibacterial, antifungal, anticancer, antidiabetic, antiinflammatory, and antioxidant effects. This study concentrates on the synthesis of two new coumarins: the first derived from rhizomes of Luvunga scandens and the second from 7-(diethylamino)-4-methyl-2H-chromen-2-one via bromination facilitated by NBS (N-bromosuccinimide) reagent. Their antibacterial and anticancer properties were evaluated in vitro, alongside in silico docking targeting the chromen-2-one group. Bromination of compound 1 yielded novel compound 2, while compound 4 was efficiently synthesized from 7-(diethylamino)-4-methyl-2H-chromen-2-one (3) using NBS. Testing on lung, breast, and liver cancer cell lines indicated that compound 2 effectively inhibited Staphylococcus aureus and Bacillus cereus at concentrations of 13.20 and 6.6 µM, respectively. It also demonstrated significant inhibition against MCF-7 breast cancer cells with a half-maximal inhibitory concentration (IC50) value of 50.37 ± 3.70 µM. Molecular docking revealed compound 2’s interaction with 2VF5 enzyme, elucidating its bacterial inhibition mechanism, with Gibbs energy and inhibition constant values of –7.42 kcal mol–1 and 3.62 µM, respectively. Additionally, compound 2 exhibited anticancer activity via alignment with topoisomerase 1 (3TOP): 1T8I, supported by molecular dynamics simulations illustrating strong ligand interactions. Analysis of pharmacophore kinetics highlighted the complex’s hydrophilic nature, indicating its potential therapeutic efficacy.