Research Projects

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for treating acute and chronic inflammatory diseases. Their anti-inflammatory activity is primarily due to the reversible inhibition of cyclooxygenases (COX-1 and COX-2) that catalyze the biosynthesis of prostaglandins from arachidonic acid. The COX-2 isoform is mainly induced at inflammatory sites, promoting inflammation and pain. However, most prescribed NSAIDs are non-selective COX inhibitors, leading to undesired side effects in gastrointestinal, renal, and cardiovascular systems. Inflammation is closely associated with cancer, and targeting and inhibiting COX-2 levels in cancer is considered an innovative strategy for controlling cancer progression. Co-administration of NSAIDs with chemotherapeutic drugs is considered a better treatment strategy with efficient drug effectiveness. However, NSAIDs are associated with off-target side effects, which can be resolved by hydrogen sulfide (H2S), a gasotransmitter with multiple beneficial impacts such as anti-inflammatory, cardioprotective, chemopreventive, and cytoprotective activities. H2S has been reported to help maintain gastrointestinal integrity and impart anti-proliferative activity up to a certain concentration. The proposed proposal aims to design stimuli-responsive turn-on fluorogenic prodrugs for adjuvant delivery of anti-inflammatory and/or anti-cancer drugs/compounds with H2S. These prodrugs will be designed to uncage the active drug with the co-delivery of H2S and turn-on fluorescence, allowing targeted delivery of active anti-inflammatory or anti-cancer drugs with minimal off-target side effects. The efficacy of these prodrugs will be studied in aqueous and cellular mediums, with the success of the proposed work potentially impacting cancer and inflammatory disease treatment strategies.