An Esterase-Sensitive Prodrug Approach for Controllable Delivery of Persulfide Species
A strategy to deliver a well-defined persulfide species in a biological medium is described. Under near physiological conditions, the persulfide prodrug can be activated by an esterase to generate a “hydroxymethyl persulfide” intermediate, which rapidly collapses to form a defined persulfide. Such persulfide prodrugs can be used either as chemical tools to study persulfide chemistry and biology or for future development as H2S-based therapeutic reagents. Using the persulfide prodrugs developed in this study, the reactivity between S-methyl methanethiosulfonate (MMTS) with persulfide was unambiguously demonstrated. Furthermore, a representative prodrug exhibited potent cardioprotective effects in a murine model of myocardial ischemia-reperfusion (MI/R) injury with a bell shape therapeutic profile.
Zheng, Yueqin,Yu, Bingchen,Li, Zhen,Yuan, Zhengnan,Organ, Chelsea L.,Trivedi, Rishi K.,Wang, Siming,Lefer, David J.,Wang, Binghe
supporting information
p. 11749 - 11753
(2017/09/20)
Generation of reactive oxygen species by a persulfide (BnSSH)
Hydropersulfides (RSxSH) have been implicated as important intermediates in the cell-killing action of the anticancer natural products leinamycin and varacin. It has been suggested that persulfides can mediate the conversion of molecular oxygen to reactive oxygen species (O2 .-, H2O2, and HO.). Here, experiments with synthetic benzyl hydrodisulfide (BnSSH) provide direct evidence that persulfides readily decompose to produce reactive oxygen species under physiologically relevant conditions.
Chatterji, Tonika,Keerthi, Kripa,Gates, Kent S.
p. 3921 - 3924
(2007/10/03)
More Articles about upstream products of 3492-66-8