Design & Synthesis of HNO Donors and their NSAID Hybrids

Abstract

HNO, the one-electron reduced congener of NO, exhibits significant therapeutic potential due to its cardioprotective, anticancer, and antioxidant properties. However, its highly unstable and reactive nature necessitates the use of donor molecules for controlled release. In this study, slow-releasing esterase-activated HNO donors were designed and synthesized to overcome the cytotoxicity observed in previous donors from our lab. Additionally, HNO-NSAID hybrids were developed to explore potential synergistic effects and to mitigate known NSAID side effects. The synthesized compounds were characterized, and their HNO release was evaluated alongside kinetic decomposition studies of the HNO-NSAID hybrid. The results demonstrated that the novel esterase-activated donors successfully released HNO, with the hybrid compound showing promising enzymatic activation, paving the way for further exploration of these molecules as therapeutic agents.