A scent of therapy: pharmacological implications of natural products containing redox-active sulfur atoms

A range of sulfur-containing natural products from plants, fungi, bacteria and animals have recently been investigated to determine their therapeutic potential. Preliminary in vitro and in vivo studies of compounds such as ergothioneine, ovothiols, allicin, leinamycin, varacin, lenthionine and diallyltetrasulfide have provided evidence for antioxidant, antibacterial, antimicrobial, antifungal and anticancer properties. The biological activity of these compounds is the result of specific chemical properties which converge in chemotypes such as thiols, disulfides, sulfenic and sulfinic acids, thiosulfinates, sulfoxides, sulfones and polysulfides. Redox-activity, catalysis, metal binding, enzyme inhibition and radical generation allow reactive sulfur species to interact with oxidative stressors, to affect the function of redox- sensitive cysteine proteins and to disrupt the integrity of DNA and cellular membranes. In some cases, the biological activity of sulfur-containing plant products depends on initial enzymatic activation, which allows thiosulfinates and isothiocyanates to be generated with high target selectivity. Not surprisingly, research into the biochemical and pharmacological properties of the lesser known sulfur chemotypes is rapidly gathering momentum.