Cystinuria is an inherited autosomal recessive disease
of the kidneys
of recurring nature that contributes to frequent urinary tract infections
due to bacterial growth and biofilm formation surrounding the stone
microenvironment. In the past, commonly used strategies for managing
cystinuria involved the use of (a) cystine crystal growth inhibitors
such as l-cystine dimethyl ester and lipoic acid, and (b)
thiol-based small molecules such as N-(2-mercaptopropionyl)
glycine, commonly known as tiopronin, that reduce the formation of
cystine crystals by reacting with excess cystine and generating more
soluble disulfide compounds. However, there is a dearth of simplistic
chemical approaches that have focused on the dual treatment of cystinuria
and the associated microbial infections. This work strategically exploited
a single chemical approach to develop a nitric oxide (NO)-releasing
therapeutic compound, S-nitroso-2-mercaptopropionyl
glycine (tiopronin-NO), for the dual management of cystine stone formation
and the related bacterial infections. The results successfully demonstrated
that (a) the antibacterial activity of NO rendered tiopronin-NO effective
against the stone microenvironment inhabitants, Escherichia
coli and Pseudomonas aeruginosa, and (b) tiopronin-NO retained the ability to undergo disulfide
exchange with cystine while being reported to be safe against canine
kidney and mouse fibroblast cells. Thus, the synthesis of such a facile
molecule aimed at the dual management of cystinuria and related infections
is unprecedented in the literature.