Design and Synthesis of Small Organic Molecules having Potential Biological Activity

Abstract

Signaling molecules come in all sizes and chemical dispositions, ranging from relatively large proteins, lipids, and peptides through biogenic amines and amino acids, to gaseous molecules. Endogenously generated gaseous molecules involved in signaling process are called “Gasotransmitters”. Gasotransmitters are endogenously generated in mammalian cells with specific substrates and enzymes; their production is regulated to fulfill signaling messenger functions. They are involved in signal transduction and have specific cellular and molecular targets. Nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S) are powerful signaling molecules that play a variety of roles in mammalian biology. Recently, cumulative evidences present sulfur dioxide (SO2) as another potential gasotransmitters. SO2 is a lipid soluble, membrane permeable gas molecule. SO2 can be generated endogenously during the metabolism of sulfur-containing amino acids such as L-cysteine. Endogenous SO2 was reported to exert a negative regulation on vascular smooth muscle cell proliferation by suppressing the Erk/MAPK pathway. Its sulfite and bisulfite derivatives also showed endothelium-independent vasorelaxation effect partially by the PGI (2)-AC-cAMP-PKA signal pathway. In addition to its physiological effects in the cardiovascular system, SO2 also showed potentials as a therapeutic agent with a variety of pathophysiological effects, including anti-hypertensive, anti-atherosclerotic, anti-oxidative, and anti-mycobacterial effects, as well as protective effects against cardiac ischemia-reperfusion (I/R) injury. Different investigations are required to explore the potentials of SO2 as gasotransmitter. These investigations include: exploration of the difference between the toxic and therape