Functionalized Derivatives of Benzo-Crown Ethers. Part 4. Antifungal Macrocyclic Supramolecular Complexes of Transition Metal Ions Acting as Lanosterol-14-alpha-Demethylase Ihibitors.

Poly- and mononuclear metal complexes of 2,3,11,12-bis[4-(10-aminodecylcarbonyl)]benzo-18- crown-6 (L) and Cu(II); Ni(II); Co(II) and Cr(III) have been synthesized and characterized by standard physico-chemical procedures. In the newly prepared complexes the crown moiety oxygen atoms of the macrocyclic host did not generally interact with metal ions, whereas the two amino groups of the ligand always did. Several of the newly synthesized compounds act as effective antifungal agents against Aspergillus and Candida spp., some of them showing activities comparable to ketoconazole, with minimum inhibitory concentrations in the range of 0.3-0.5 mug/mL. The mechanism of antifungal action of these coordination compounds is probably connected to an inhibition of lanosterol-14-alpha-demethylase, a metallo-enzyme playing a key role in sterol biosynthesis in fungi, bacteria and eukariotes.