Anti-thyroid and antifungal activities, BSA interaction and acid phosphatase inhibition of methimazole copper(II) complexes

作者：Urquiza Nora M; Islas Maria S; Ariza Santiago T; Jori Nadir; Martinez Medina Juan J; Lavecchia Martin J; Lopez Tevez Leonor L; Lezama Luis; Rojo Teofilo; Williams Patricia A M; Ferrer Evelina G^*

来源：Chemico-Biological Interactions, 2015, 229: 64-72.

DOI：10.1016/j.cbi.2014.12.036

• Methimazole
• Phenanthroline
• Copper(II)
• Antifungal activity
• Anti-thyroid activity
• BSA interactions

It has been reported that various metal coordination compounds have improved some biological properties. A-high activity of acid phosphatase (AcP) is associated to several diseases (osteoporosis, Alzheimer's, prostate cancer, among others) and makes it a target for the development of new potential inhibitors. Anti-thyroid agents have disadvantageous side effects and the scarcity of medicines in this area motivated many researchers to synthesize new ones. Several copper(II) complexes have shown antifungal activities. In this work we presented for a first time the inhibition of AcP and the anti-thyroid activity produced by methimazole-Cu(II) complexes. Cu-Met ([Cu(MeimzH)(2)(H2O)(2)](NO3)(2)center dot H2O) produces a weak inhibition action while Cu-Met-phen ([Cu(MeimzH)(2)(Phen)(H2O)(2)]Cl-2) shows a strong inhibition effect (IC50 = 300 mu M) being more effective than the reported behavior of vanadium complexes. Cu-Met-phen also presented a fairly good anti-thyroid activity with a formation constant value, K-c = 1.02 x 10(10) M-1 being 10(6) times more active than methimazole (K-c = 4.16 x 10(4) M-1) in opposition to Cu-Met which presented activity (K-c = 9.54 x 10(3) M-1) but in a lesser extent than that of the free ligand. None of the complexes show antifungal activity except Cu-phen (MIC = 11.71 mu g mL(-1) on Candida albicans) which was tested for comparison. Besides, albumin interaction experiments denoted high affinity toward the complexes and the calculated binding constants indicate reversible binding to the protein.

• 出版日期2015-3-5