Capreomycin--a polypeptide antitubercular antibiotic with unusual binding properties toward copper(II).

Capreomycin is an important therapeutic agent having intriguing and diverse molecular features. Its polypeptidic structure rich in nitrogen donors makes the drug a promising chelating agent for a number of transition metal ions, especially for copper(II). The results of the model investigational studies suggest that capreomycin anchors Cu(2+) ion with an amino function of the α,ß-diaminopropionic acid residue at pH around 5. At physiological pH copper(II) ion is coordinated by two deprotonated amide nitrogen atoms of the α,ß-diaminopropionic acid, the serine residue as well as the amino function deriving from the ß-lysine. Above that pH value we observe a rearrangement within the coordination sphere leading to movement of Cu(2+) to the center of the peptide ring with concurrent coordination of four nitrogen donors. Spin-lattice relaxation enhancements and potentiometric measurements clearly indicate that deprotonated amide nitrogen atom from the ß-ureidodehydroalanine moiety is the fourth donor atom.

Biological activity and structure dependent properties of cuprous iodide complexes with phenanthrolines and water soluble tris (aminomethyl) phosphanes.

This paper presents the biological activity of copper(I) iodide complexes with 1,10-phenanthroline (phen) or 2,9-dimethyl-1,10-phenanthroline (dmp) and three tris (aminomethyl) phosphanes: P(CH2N(CH2CH2)2NCH3)3 (1), P(CH2N(CH2CH2)2O)3 (2) and P (CH2N(CH3)CH2CH2OH)3 (3). Crystallographic and DFT data indicate a significantly stronger binding ability of 3 in the complexes [CuI (phen) P (CH2N (CH3)CH2CH2OH)3] (3P) and [CuI(dmp)P(CH2N(CH3)CH2CH2OH)3] (3N) in comparison to the 1 or 2 ligands. Most probably, this is caused by the relatively small steric requirements of 3. The complexes with dmp exhibit a very high in vitro activity against the Staphylococcus aureus strain (MIC - minimal inhibitory concentration: 2.5-5 µg/mL) and Candida albicans diploid fungus (MIC: 1.25-2.5 µg/mL). All the tested complexes also show a strong in vitro antitumor activity against human ovarian carcinoma cell lines: MDAH 2774 (IC50: 7-2 µM) and cisplatin-resistant SCOV3 (IC50: 3-2 µM). Interestingly, the complexes with dmp of higher biological activity more weakly interact with bovine serum albumin (BSA) and less efficiently cleave the pBluescriptSK+ plasmid.