New molecule may reduce cellular damage after heart attack

LOS ANGELES, Jan 1:  Scientists have developed molecules with the potential to deliver healing power to stressed cells – such as those involved in heart attacks, cancer and Alzheimer’s disease.

The research – done at a cellular level in the lab – involves the design of organic molecules that break down to release hydrogen sulphide when triggered by specific conditions such as increased oxidative stress.

Oxidative stress damages cells and is tied especially to heart disease and cancer, as well as Alzheimer’s and Parkinson’s disease.

“We have discovered that small organic molecules can be engineered to release a molecule called carbonyl sulphide, which is the most prevalent sulphur-containing molecule in the atmosphere, but more importantly converts rapidly to hydrogen sulphide under biological conditions,” said Michael Pluth, professor at University of Oregon in the US.

“We developed and demonstrated a new mechanism to release small molecules that provide therapeutic hydrogen sulphide,” said Pluth.

Hydrogen sulphide, a colourless gas, has long been known for its dangerous toxicity – and its telltale smell of rotten eggs – in the environment, but it also is produced in mammals, including humans, with important roles in molecular signalling and cardiac health.

Researchers used benzyl thiocarbamates to design responsive organic molecules that release carbonyl sulphide.

They adapted the molecule so it remains nontoxic and stable until cellular conditions trigger it to release the carbonyl sulphide, which is converted to hydrogen sulphide by carbonic anhydrase enzymes in the body.

Finding a way to generate restorative hydrogen sulphide in the body has been a goal of many research labs around the world in the last two decades.

Researchers in 2013 developed a probe that detects the gas in biological samples, providing a framework to test potential donor molecules, either synthetically produced or isolated from natural products.

“To do that we need to develop new chemistry. We are synthetic chemists. We make molecules with the goal of developing new research tools or therapeutic tools,” said Pluth.

“As for treating a disease, we are not there yet, but these cell-based studies suggest that those types of protective effects might be possible,” he said.

During a heart attack or loss of blood flow, for example, increased levels of reactive oxygen species like hydrogen peroxide emerge, he added.

The recently developed donor molecules are programmed to react to the overexpression of reactive oxygen species.

Current hydrogen sulphide donors are generally slow-release molecules that donate hydrogen sulphide passively.

The research shows that it is possible to build molecular scaffolds to release carbonyl sulphide and then hydrogen sulphide by creating a trigger in the molecule to start the delivery process, researchers said. (AGENCIES)