Design synthesis and evaluation of bioactivable organic donors of sulfur dioxide

Abstract

Sulfur dioxide SO2 is colourless pungent gas and has long been considered as a toxic pollutant but has recently emerged as a possible mediator of cellular signaling SO2 is widely used as a food preservative and as an antibacterial agent in winemaking SO2 is produced endogenously by metabolism of sulfur containing amino acids and by oxidation of H2S In aqueous media SO2 gets hydrated forms sulfite and bisulfite In order to study physiological roles of SO2 typically inorganic or organic sources of SO2 are used To investigate precisely several untapped roles of SO2 in biological system tools that generate SO2 inside cell in a reliable and controllable manner are needed Hitherto few chemical tools have been known to generate SO2 and they all have certain limitations that we proposed to address Our lab for the very first time previously has reported thiol activated SO2 donors and their biological activity against Mycobacterium tuberculosis Mtb Structural modifications for thiol activated SO2 donors led us to a new set of compounds that were excellent inhibitors of Staphylococcus aureus S aureus Together we have developed chemical tools for SO2 donation based on diverse activation mechanisms with potential applications as antibacterials Next we describe efforts towards the new and improved SO2 donors First we designed and synthesized a series of esterase sensitive SO2 donors These compounds undergo self immolation to generate SO2 upon exposure to esterase an enzyme that is widely prevalent in cells Using this design as a prototype we next directed the delivery of SO2 to bacteria using the bacterial enzyme nitroreductase The strategy was adapted to co deliver SO2 and a clinically used antibiotic In this strategy we presented the design and synthesis of a nitroreductase stimuli specific fluoroquinolone conjugated novel class of prodrugs In this approach we synthesized theranostic prodrug of ciprofloxacin as therapeutic with coumarin fluorophore for real time monitoring for drug release newline newline