Potential of Pyridine Amphiphiles as Staphylococcal Nuclease Inhibitor

The present study explores the potential of pyridine-based synthetic amphiphiles C1 and C2 having 4-carbon and 12-carbon hydrophobic tails, respectively, as staphylococcal nuclease inhibitors. UV-visible titration with calf-thymus DNA (CT-DNA) revealed a hypochromic shift in the absorbance bands of C1 and C2, whereas fluorescence titration indicated a reduction in the emission intensity of the monomer bands of the amphiphiles. Interaction of deoxyribonuclease I (DNase 1) and micrococcal nuclease (MNase) with C1 or C2 led to a decrease in the emission intensity of tryptophan at λ=345 nm along with an increase in the monomer emission intensity of C1 and C2 at λ=375 nm for DNase I and excimer emission intensity at λ=470 nm for both DNase I and MNase. Scatchard's analysis indicated superior interaction of C2 with DNase I. Circular dichroism spectroscopy revealed major changes in the secondary structures of both DNase I and MNase upon interaction with the amphiphiles. A solution-based nuclease assay in conjunction with gel electrophoresis indicated amphiphile-mediated protection against nuclease-directed DNA cleavage. Interestingly, C2 could render inhibition of nuclease present in the culture supernatant of Staphylococcus aureus MTCC 96, which highlights the therapeutic prospect of the amphiphile against S. aureus.