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The &#8216;superbug&#8217; infection caused by metallo-&#946;-lactamases (M&#946;Ls) has grown into an emergent health threat. Given the clinical importance of M&#946;Ls, a novel scaffold, dithiocarbamate, was constructed. The obtained molecules, DC1, DC8 and DC10, inhibited M&#946;Ls NDM-1, VIM-2, IMP-1, ImiS and L1 from all three subclasses, exhibiting an IC₅₀ &lt; 26 &#956;M. DC1 was found to be the best inhibitor of ImiS (IC₅₀ &lt; 0.22 &#956;M). DC1-2, DC4, DC8 and DC10 restored antimicrobial effects of cefazolin and imipenem against <i>E. coli</i>-BL21, producing NDM-1, ImiS or L1, and DC1 showed the best inhibition of <i>E. coli</i> cells, expressing the three M&#946;Ls, resulting in a 2-16-fold reduction in the minimum inhibitory concentrations (MICs) of both antibiotics. Kinetics and isothermal titration calorimetry (ITC) assays showed that DC1 exhibited a reversible, and partially mixed inhibition, of NDM-1, ImiS and L1, with Ki values of 0.29, 0.14 and 5.06 &#181;M, respectively. Docking studies suggest that the hydroxyl and carbonyl groups of DC1 form coordinate bonds with the Zn (II) ions, in the active center of NDM-1, ImiS and L1, thereby inhibiting the activity of the enzymes. Cytotoxicity assays showed that DC1, DC3, DC7 and DC9 have low toxicity in L929 mouse fibroblastic cells, at a dose of up to 250 &#956;M. These studies revealed that the dithiocarbamate is a valuable scaffold for the development of M&#946;Ls inhibitors.