Antimicrobial resistance is an increasingly serious threat to global public health that requires innovative solutions to counteract new resistance mechanisms emerging and spreading globally in infectious pathogens. Classic organic antibiotics are rapidly exhausting the structural variations available for an effective antimicrobial drug and new compounds emerging from the industrial pharmaceutical pipeline will likely have a short-term and limited impact before the pathogens can adapt. Inorganic and organometallic complexes offer the opportunity to discover and develop new active antimicrobial agents by exploiting their wide range of three-dimensional geometries and virtually infinite design possibilities that can affect their substitution kinetics, charge, lipophilicity, biological targets and modes of action. This review describes recent studies on the antimicrobial activity of transition metal complexes of groups 6–12. It focuses on the effectiveness of the metal complexes in relation to the rich structural chemical variations of the same. The aim is to provide a short vade mecum for the readers interested in the subject that can complement other reviews.

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<p>Preparation of a series of ten 3-arylcoumarin molecules, their respective <i>fac</i>-[Re(CO)₃(bpy)L]⁺ and <i>fac</i>-[Re(CO)₃(L⁀L)Br] complexes. All compounds were tested for their antimicrobial efficacy. Whereas the 3-arylcoumarin ligands are virtually inactive against the human-associated pathogens with minimum inhibitory concentrations (MICs) > 150 µM, when coordinated to the <i>fac</i>-[Re(CO)₃]⁺core, most of the resulting complexes showed remarkable antibacterial potency<i>. </i>Several rhenium complexes exhibit activity in nanomolar concentrations against Gram-positive pathogens such as <i>Staphylococcus aureus</i> strains, including methicillin-resistant <i>S. aureus</i> (MRSA) and <i>Enterococcus faecium</i>. The molecules do not affect bacterial cell membrane potential, but some of the most potent complexes strongly interact with DNA, indicating it as a possible target for their mode of action. <i>I</i><i>n vivo </i>studies in the zebrafish model showed that the complexes with anti-staphylococcal/MRSA activity were non-toxic to the organism even at much higher doses of the corresponding MICs. In the zebrafish-MRSA infection model, the complexes increased the survival rate of infected fish up to 100 % and markedly reduced bacterial burden. Moreover, all rescued fish developed normally following the treatments with the metallic compounds.</p>

We have explored the possibility of using organometallic derivatives of cobalamin as a scaffold for the delivery of the same antimalarial drug to both erythro- and hepatocytes. This hybrid molecule approach, intended as a possible tool for the development of multi-stage antimalarial agents, pivots on the preparation of azide-functionalized drugs which, after coupling to the vitamin, are released with a 4-(4-ethynylphenyl)-triazole functionality. Three chloroquine and one imidazolopiperazine derivative (based on the KAF156 structure) were selected as model drugs. One hybrid chloroquine conjugate was extensively studied via fluorescent labelling for in vitro and in vivo bio-distribution studies and gave proof-of-concept for the design. It showed no toxicity in vivo (zebrafish model) as well as no hepatotoxicity, no cardiotoxicity or developmental toxicity of the embryos. All 4-(4-ethynylphenyl)-triazole derivatives of chloroquine were equally active against chloroquine-resistant (CQR) and chloroquine-sensitive (CQS) Plasmodium falciparum strains.