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Maintenance of redox homeostasis is essential for cellular survival and growth. Small gaseous entities which are reactive biological species derived from oxygen, nitrogen as well as sulfur are generated and quenched during these processes. These small gaseous molecules mediate a number of cellular processes and signalling events. The major challenges in this field include reliable detection, controlled generation as well as inhibition of biosynthesis of these species. Our lab works on developing tools to study these complex biological processes in a systematic manner. Using fundamental and mechanistic organic chemistry as the basis, we design and develop small molecules that can fragment to produce the aforementioned species.
Reactive Oxygen Species (ROS)
Superoxide radical is inadvertently generated during respiration and it is subsequently converted to hydrogen peroxide. Fenton chemistry produces hydroxyl radical, which can cause extensive damage to various cellular components. While ROS is considered as a cancer therapeutic, the role of ROS in bacteria has recently become controversial with a number of studies indicating that ROS can inhibit bacterial growth. Our lab works on developing new methodologies to generate ROS including the use of natural product-based scaffolds. We intend to develop new strategies to target Mycobacterium tuberculosis and Methicillin-resistant Staphylococcus aureus.
Reactive Sulfur Species (RSS)
Together with nitric oxide and carbon monoxide, hydrogen sulfide is now considered as the third gasotransmitter. Our lab is developing new sources of hydrogen sulfide. Sulfur dioxide is a product of oxidation of hydrogen sulfide and is used routinely in the food industry as a preservative and antibacterial agent. Our lab is developing new sources of sulfur dioxide to study is biological effects as well as to explore its therapeutic potential. We find that thiol-activated sources of sulfur dioxide are capable of inhibiting Mycobacterium tuberculosis at low micromolar levels.
Reactive Nitrogen Species (RNS)
Nitric oxide (NO) was long considered an environmental pollutant but in the past three decades, NO has been found to mediate numerous cellular processes. Due to its ability to cause biomacromolecular damage, the use of NO as a therapeutic has been suggested. However, a major challenge associated with the use of NO is to direct its delivery. Our lab develops new methodologies for directed delivery of NO. For example, we are developing methods to produce NO in certain unique cellular situations such as hypoxia which is characterized by a reducing environment. Furthermore, our lab is also working on developing new tools to study cellular responses to peroxynitrite.