Identification of biosimilar for trimethoprim-andrographis paniculata phytochemicals inhibits dihydrofolate reductase (Dhfr)

Abstract

Staphylococcus aureus a pathogenic bacterium responsible for hospital and community-acquired infections. Trimethoprim is generally administrated for treating S.aureus infection in combination with sulfamethoxazole. But increasing antimicrobial resistance towards antibiotics is a major concern. Trimethoprim targets Dihydrofolate reductase (DHFR), a crucial enzyme involved in nucleic acid and amino acid biosynthesis pathways. DHFR catalyzes the conversion of dihydrofolate to tetrahydrofolate using NADH as a cofactor. Andrographis paniculata is a traditionally used medicinal plant for treating various ailments, including microbial infections. More than 25 bioactive phytochemicals have been reported to exhibit various activities. The aim of the present study is to identify the lead phytochemical(s) mediating antimicrobial property of A. paniculata by using computational analysis. Molecular docking of A.paniculata phytochemicals with wild and mutated DHFR were performed. Results reveal phytochemicals interact and exhibit strong binding affinity with active site residues of wild and mutated strains. 14-deoxy-11-oxoandrographolide showed binding energy greater than 10 kCal/mol with both strains. Further analysis of A. paniculata phytochemicals for their efficacy would lead to the development of potential drugs for the treatment of microbial infections.