Synthesis, antimicrobial, DNA binding, and computational studies of some bis- and poly(4-methyl-2H-chromen-2-one) derivatives

Abstract

The research focused on studying how 7-hydroxy-4-methyl-2H-chromen-2-one can be used as a building material for new bis- and poly(coumarins) through alkylation with related bis- and poly(halo) compounds. Spectroscopic techniques confirmed the chemical compositions of these compounds. An experiment was conducted to assess the effectiveness of new coumarin derivatives in inhibiting the growth of various harmful bacterial strains in a controlled environment. Among the recently formed compounds, tris-coumarin 19 and bis-coumarin linked to thienothiophene core 26 demonstrated notable antibacterial effectiveness against the bacteria examined. Compounds 19 and 26 were evaluated for their interactions with CT-DNA using UV-Vis spectroscopy, resulting in a significant decrease in absorbance intensity with a slight shift towards longer wavelengths. Research using computer simulations of molecular docking indicates that compounds 19 and 26 can effectively attach to different target proteins such as DNA gyrase, dihydropteroate synthase, MurE ligase, and dihydrofolate reductase, achieving binding scores ranging from -9.76 to -6.68 kcal/mole. This indicates that our derivatives can prevent these proteins and display significant antibacterial characteristics. Additionally, assessments were done on compound 19 for drug-likeness and compound 26 for ADMET properties, indicating their potential as valuable candidates for further drug development.