NATURAL IRON SEQUESTERING AGENTS: THEIR ROLES IN NATURE AND THERAPEUTIC POTENTIAL

Iron is one of the essential elements involved in many cellular processes that are necessary for life, including oxygen sensing, oxygen transport, electron transfer, energy metabolism, DNA synthesis etc. Although, iron is not readily available in the naturally available iron III form, microorganisms have evolved to produce smaller high affinity chelating small organic molecules called siderophores for its acquisition. The study of siderophores has opened up investigations of small-molecule inhibitors, which can hinder the biosynthesis of siderophores and thereby suppress the growth and virulence of bacteria in iron-limiting backgrounds. One of the most important applications of siderophores is selective drug delivery to defeat drug-resistant bacteria. It uses the iron transport capabilities of siderophores in carrying drugs/molecules into cells, synthetic through conjugates between siderophores and antimicrobial agents forming sideromycins. Some siderophore such as Desferrioxamine B have been found to be useful in the treatment of malaria caused by Plasmodiumfalciparum through intracellular iron depletion mechanisms. Importantly, iron overload diseases can be efficiently treated with siderophore based drugs as they can quench iron effectively. Moreover, siderophores such as dexrazoxane, desferriexochelins, isonicotinoyl hydrazine derivatives are being used in cancer therapy, as they prevent the formation of free radicals by reducing iron and retard the tumor growth by disturbing the iron regulation in tumor cells. In addition to bacterial siderophores, it is reported that plant-derived polyphenols, phenolic acids,and flavonoid compounds show siderophores like activity scavenging iron which gives rise to their antioxidant and anticancer activity.