Chemotherapy and drug drug design

Cytoplasmic iron is in the reduced form and therefore ready to undergo oxidation. If nearby lipids are peroxidised, DNA and other macromolecules can be damaged (MacKenzie et al, 2007). This makes severe iron overload and iron deficiency equally disastrous. The concentration of iron in mammalian tissues is not very high because the iron is sequestered by several host proteins like serum transferrin and lactoferrin and is not readily available. The microorganisms which invade the body compete with transferrin for the iron. Secreting siderophores which bind with iron has the property of preventing invasion by pathogenic bacteria (Crossa and Payne, 2004). The growth and multiplication of microorganisms are hindered in the presence of iron present at physiological ph of the body as its solubility is poor. An organism which cannot avail of iron from its many sources would be unsuccessful as a pathogen. Gram negative microorganisms are recognized by the complexes of iron and siderophores at the specific outer membrane receptors. In Gram positive organisms, the iron-siderophore complexes are recognized by the specific binding proteins.
Both Gram positive and Gram negative bacteria take the iron from heme (Crossa and Payne, 2004). Gram negative bacteria use two methods. One is the binding to the outer membrane receptors and periplasmic binding of ABC permeases. The secretion of specialized bacteria proteins sequesters heme from other sources in the second method. Proteins acting like siderophores are called hemophores. Hemophilus influenza is known to have hemophores which captures free heme or from haemoglobin or heme from hemopexin. Pseudomonas organisms and Yersinia pestis are known to have a second hemophore system (Crossa, 2004). Erythropoiesis, immune functions and oxidative metabolism use iron (Munoz et al, 2009). Erythropoiesis is the production of red blood cells (RBCs) or erythrocytes, one of the many types of cells in the blood. The daily turnover of 1011 RBCs in the normal adult is possible through the iron. If damage occurs to RBCs by hemolysis or haemorrhage, the production is stepped up as a rapid response. The question of overproduction never arises as the erythropoiesis is well-regulated by key regulatory proteins to maintain the number of circulating RBCs within a normal range (Munoz et al, 2009, MacKenzie, 2007). The stem cell changes into the burst forming unit erythroid in the bone marrow in the first step of the formation of RBCs. The stages from the burst-forming unit erythroid to the orthochromatic erythroblast are influenced by erythropoietin. The orthochromatic erythroblast changes into reticulocytes circulating in the blood to become mature RBCs in another day. For the differentiation and maturing into RBCs, iron is an essential component along with vitamin B12 and folate. Oxidative metabolism Many metabolic processes essentially requires iron for their functions but an excess of iron also can cause damage to the cells through oxidative stress by the release of free hydroxyl radicals which are reactive and harmful (He et al, 2007, MacKenzie et al, 2007). Iron is absorbed but cannot be excreted