Design and Synthesis of Nitroreductase activated HNO Donor

Abstract

HNO, which is the 1-e - reduced form of NO, has recently been reported to enhance the antimycobacterial activity of anti-TB drugs like Rifampicin, enhance H2O2 mediated bacterial cell killing, increase the RSS levels in various bacterial cells such as S. Aureus. However, the HNO donor, Angeli’s salt used in these studies concomitantly release Nitrite (NO2) which may complicate the conclusions. Also, the esterase activated HNO donors reported from our lab, has shown high antibacterial activity (micromolar MIC values), however, also showed equal cytotoxic nature. We hypothesized that this cytotoxic nature of these donors can be bypassed by changing the trigger for HNO release from an ubiquitous esterase trigger to a more bacteria specific trigger, such as nitroreductase enzyme. In this project, we designed and synthesized nitroreductase activated HNO donors and evaluated the HNO release from them.