Dapsone resistance is a serious impediment to the implementation of the present
leprosy control strategies. In the recent past, many studies have been undertaken to address the
antibiotic activity and binding pattern of
dapsone against both native and mutant (Pro55Leu) folP1. Yet, there is no well-developed structural basis for understanding
drug action and there is dire need for new antibacterial
therapies. In the present study, molecular simulation techniques were employed alongside experimental strategies to address and overcome the mechanism of
dapsone resistance. In essence, we report the identification of small molecule compounds to effectively and specifically inhibit the growth of M. leprae through targeting
dihydropteroate synthase, encoded by folP1 which is involved in
folic acid synthesis. Initially, ADME and toxicity studies were employed to screen the lead compounds, using
dapsone as standard
drug. Subsequently, molecular docking was employed to understand the binding efficiency of
dapsone and its lead compounds against folP1. Further, the activity of the screened lead molecule was studied by means of molecular dynamics simulation techniques. Furthermore, we synthesized 4-(2-fluorophenylsulfonyl)benzenamine, using (2-fluorophenyl)boronic
acid and 4-aminobenzenesulfonyl
chloride, and the compound structure was confirmed by (1)H NMR and (13)C NMR spectroscopic techniques. Most importantly, the antibacterial activity of the compound was also examined and compared against
dapsone. Overall, the result from our analysis suggested that CID21480113 (4-(2-fluorophenylsulfonyl)benzenamine) could be developed into a promising lead compound and could be effective in treating
dapsone resistant
leprosy cases.