Abstract:
Hydrogen sulfide (H2S) is an endogenous gaseous signaling molecule, which mediates
cardiovascular homeostasis and exhibits antioxidant activity. When H2S was
administered along with non-steroidal anti-inflammatory drugs (NSAIDs), in animal
models, the side effects associated with NSAIDs were reduced. With the growing
importance of H2S as a signaling molecule, new and effective methods are needed for
its production and detection. This lead to the development of H2S donors, which could
release H2S in a controlled and targeted manner inside the cells. Over the years, a
number of analytical techniques for release and detection have been reported.
However these techniques are associated with some limitations such as lack of
selectivity between H2S and other biological thiols, rapid oxidation on air exposure,
consumption of H2S and production of toxic by-products. Thus development of a H2S
donor with an inbuilt reporter would be useful. In this respect, aim of the project is to
design of one such H2S donor, which can give direct release of H2S, with a concurrent
fluorescence signal. It will minimize the reliability on secondary assay for H2S detection.
With nitro-reductase as the enzyme trigger and umbelliferone as fluorescence reporter,
we tried to study the release of H2S. The design also addresses the production of
potential toxic by-products. Following some synthetic difficulties, we modified the
fluorescence reporter to 3-hydroxy-6H-benzo[c]chromen-6-one and studied the release
of H2S.