Sulfur is the most common atom in small molecule medicines after oxygen and nitrogen, and a quarter of the most prescribed small molecule drugs are organosulfur compounds. At the functional group level, more than 37% of all FDA-approved organosulfur drugs contain the sulfonyl group, emphasizing the importance of this particular group in drug design. Organosulfur compounds are widely present in our bodies: some example are the aminoacids cysteine, methionine and taurine, vitamin B1 (thiamine) and the major cellular antioxidant glutathione (GSH). They are also widespread in the natural environment, being found garlic, onions, shallots, broccoli, cauliflower, turnip and similar vegetables. Medical research finds that when consumed, they can protect against cancer, heart disease and even diabetes. There is also evidence of these compounds’ antiviral and antibacterial uses. About a quarter of all pharmaceutical drugs currently contain sulfur in their structure; just think that penicillins and their derivative antibiotics called cephalosporins have at least one suflur atom in their structure. However, the use of sulfur atoms in the manufacturing of drugs is a double-edged sword.
Sulfur is tricky to introduce into a molecule because currently available chemical tools do not allow researchers to introduce sulfur into molecules with high levels of precision. There are challenges to the current synthetic methods that are used to make organosulfur compounds, For example, chemists often struggle to synthesize organosulfur compounds with a specific structural geometry. Usually, existing syntheses result in mixtures of products of different chemo-, regio- and stereo- isomers. Compounds with different chemo-, regio- and stereo- structures are made by the same types and numbers of atoms, but assembled in different ways. This shortcoming impacts scientists’ ability to make molecules that can one day become medicines, as well as the eventual efficacy of future drugs that rely on a particular geometry of synthetic sulfur molecules. UTSA has launched research that aims to solve this roadblock to expedite new drug development. Chemistry intends to develop methods to improve the outcome of synthesizing these sulfur-containing products with specific chemo-, regio- and stereoselectivity.
UTSA researchers plan to use intermediate oxidation states of organosulfur reagents, in particular sulfinates, to solve the industry’s limitations of current methods including the lack of efficient methods to synthesize sulfinates directly from abundant precursors. The UTSA group will use more than $1 million in funding from the National Institutes of Health to improve the development of these therapeutic agents. Their end goal is to build a broad range of synthetic sulfur-containing molecules that will become readily accessible for organic synthesis and drug discovery applications. Larionov’s research group focuses on complex molecule synthesis with a special focus on compounds targeting cancer. It’s expected that this research will yield results in four years. Figuring out how to improve the use of sulfur in drug development also has implications beyond medicine. Improving the use of OSCs can advance functional materials such as photovoltaics, organic electronics, carbon materials, nanotechnology, liquid crystals, magnetic materials, surfaces and interfaces, and biomaterials.
- Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
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