Synthesis, characterization and unravelling the molecular interaction of new bioactive 4-hydroxycoumarin derivative with biopolymer: Insights from spectroscopic and theoretical aspect.

In the progress of small molecule as drug candidates, 4-hydroxycoumarin based compounds bearing a crucial place as potent antibiotic agents with appreciable safety in drug invention. Being synthetically and easily obtainable, 4-hydroxycoumarin related compounds with planar structure have been promoted predominantly as DNA targeting agent. Nevertheless, here we elucidate the synthesis, characterization and theoretical study of bio-active small molecule 4-hydroxy-3,4'-bichromenyl-2,2'-dione (4HBD). Then we have illuminated the binding interactions of 4HBD with calf thymus DNA (ctDNA), which is particularly designed for biological application. Extensive investigations of the binding of 4HBD with ctDNA are provided by utilizing multi-spectroscopic and molecular docking approaches, including UV-vis absorbance, steady-state, time-resolved fluorescence spectroscopy and circular dichroism study. The calculated binding and quenching constant value from quantitative data analysis of absorption and emission spectroscopy shows that 4HBD binds to the ctDNA groove. Further confirmation of the same is found by comparative displacement and iodide quenching studies. Negative enthalpy, negative free energy and positive entropy change imply a hydrophobic force monitors the association of 4HBD with the biomacromolecule. Interestingly the small molecule (4HBD) shows potential anti-bacterial activity against the model pathogenic gram-negative (Escherichia coli and Pseudomonas aeruginosa) and gram-positive (Bacillus subtilis and Staphylococcus aureus) bacteria. The noncytotoxic nature of the 4HBD is demonstrated in vitro with the help of MTT assay by normal kidney epithelial (NKE), breast cancer cells (MCF-7) and human prostate cancer cell (PC3) lines. Hemolytic assay exhibits insignificant hemolysis of human erythrocyte cells at the minimum inhibitory concentration (MIC) of these tested bacteria. In this regard the present invention of 4-hydroxycoumarin based antimicrobial and noncytotoxic 4HBD molecule holds future promise in the development of new antibiotics.