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In order to maintain the capacity to treat infections it is necessary to adopt strategies for the development of new drugs. The use of metal ions in medicine for their antimicrobial effects was prevalent for many years before the advent of antibiotics. During the second half of the twentieth century, active metal complexes with different chemical, physicochemical and biochemical properties than the constituents reborn by the threat posed by microbial multidrug resistance. In this review, essential transition metal drugs with Cu(II), Zn(II) and Fe(III), showing known chemical structure, antimicrobial activities better than the free ligands and reported in the last ten years, are presented. The scientific information realizes many metal complexes having antimicrobial activity, which covers Gram negative and Gram positive bacteria, mycobacteria, yeast and fungi and many of them would be good candidates for further pharmaceutical studies. For these reasons the strategy of metal coordination is a potent tool to get numerous and diverse new antimicrobial agents. the development of new drugs. The strategies proposed include the reduction of antimicrobials demand, through vaccination, improving water and sanitation and a supply of food free from bacterial pathogens; the development of new ways to treat infectious, like antibiotic cycling, finding agents that renew the antibacterial currently in use and bacteriophages therapy; and the search for new antimicrobials to treat low but growing numbers of MDR microbial infections [1]. With this aim, organic chemists have synthesized analogues and modifications or derivatives of existing organic compounds [2] or have researched on novel structures which microorganisms have never been exposed. This is the case of bedaquiline, the first drug in a new class of anti-Tuberculosis (TB) medications to be approved in more than 40 years by the US Food and Drug Administration [3]. Other strategies are the development of inhibitors that are coadministrated with antibiotics to neutralize resistance mechanisms; the search for natural occurring compound in bacteria, in plants, in the marine world and through the novel growth of uncultured microorganism; the search for synergistic action between older antimicrobials and between antimicrobial and essential oils; the search of entire genomes for new antibacterial targets; and new formulations of metals-based compounds for use as antimicrobial agents alterative to antibiotics. This last strategy is of interest in this report [4-7]. The use of metal compounds in medicine for their antimicrobial effects was prevalent for many years before the advent of antibiotics. These antibiotics were almost exclusively based on synthetic and natural organic products. Despite the recognition of the pharmacological properties of metal ions, scarce attention has been given to inorganic substances. However, during the second half of the twentieth century the use of molecules or ions coordinated with metals reborn by the threat posed by microbial MDR and became a good tool to provide new pharmacological active molecules [8]. This strategy was used in several areas of the pharmacology. In spite of the fact that metal-based drugs represent a relatively small percentage of total drugs, they fulfill important roles in medicine. Just consider the cisplatin (platinum-containing anti-cancer drug), the aurothioglucose (chrysotherapy for the treatment of rheumatoid arthritis) and the Ag-sulfadiazine (silver complex with antibacterial activity used in burns) to realize the importance of this field [9-11]. Introduction The research for new and better antimicrobial compounds is an important field due to different factors. The use of invasive medical procedures and extensive surgeries, the increase of immune compromised patients, among others, can affect the incidence of infections. Another big problem associated is that treatment of infectious diseases is being seriously hampered by the emergence and spread of microbial resistance. While the majority of human pathogens remain sensitive to antimicrobials, multi drug resistant (MDR) pathogens have emerged, being antimicrobial use the driving force behind their appearance. Frequently MDR bacteria are common cause of hospital infections, causing some community acquired infections too, and some strains are resistant to all current available antimicrobial. This phenomenon is the result of the microorganism ability to find a quick response to overcome an adverse environment through mutation and acquisition of new genes [1]. In order to maintain the capacity to treat infections it is necessary to adopt strategies that prevent or delay the development of resistance and preserve the efficiency of actual or new antimicrobials and

Essential Transition Metal Ion Complexation as a Strategy to Improve the Antimicrobial Activity of Organic Drugs