Title : Exploring the plant-derived natural antimetabolites against pathogenic bacteria: in silico approaches of drug discovery in combating bacterial infection to humans
Emergence of multiple antibiotic resistance among pathogenic bacteria, and lack of suitable antibiotic choice to combat them highlight the urgent need of effective alternatives for the treatment of such bacterial infection to humans. Phytochemicals have been considered as the most useful components of lead molecules in drug discovery. The current study performs in silico molecular docking of phytochemicals from sweet cherry (Prunus avium) and pigeon pea (Cajanus cajan), targeting bacterial enzymes: dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) useful in nucleic acid biosynthesis among bacteria. The phytochemicals (small-molecules) which were utilized as the ligands in docking studies included caffeic acid, p-coumaric acid, sinapic acid and ferulic acid from Prunus avium, and cajaisoflavone, cajaflavanone and cajanone from Cajanus cajan. The anti-DHFR trimethoprim (TMP) and anti-DHPS sulfamethoxazole (SMZ) were used as the reference standards in molecular docking. The molecules studied through docking were then subjected to pharmacological property analysis. The top-scored ligands were selected for molecular dynamic simulation to authenticate the thermodynamically stable binding with the target proteins. The overall findings of the current study signify the usefulness of the phytochemicals as natural antimetabolites against human pathogenic bacteria, and this would also be valuable in aiding precise drug discovery from phytochemicals with systematic pharmacological understanding.