title: Anti-thyroid and antifungal activities, BSA interaction and acid phosphatase inhibition of methimazole copper(II) complexes.
abstract: 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·H2O) produces a weak inhibition action while Cu-Met-phen ([Cu(MeimzH)2(phen)(H2O)2]Cl2) shows a strong inhibition effect (IC50 = 300 μM) 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, Kc=1.02 × 10(10)M(-1) being 10(6) times more active than methimazole (Kc = 4.16 × 10(4)M(-1)) in opposition to Cu-Met which presented activity (Kc=9.54 × 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 μgmL(-1) on Candidaalbicans) 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.
authors: Cátedra de Química Analítica, Instituto de Química Analítica, Facultad de Bioquímica, Química y Farmacia, Universidad Nacional de Tucumán, Ayacucho 471, 4000 San Miguel de Tucumán, Argentina.
authors: Nora M
authors: NM
authors: Urquiza
authors: Centro de Química Inorgánica (CEQUINOR/CONICET, UNLP), Facultad de Ciencias Exactas, UNLP, C. Correo 962, 1900 La Plata, Argentina.
authors: María S
authors: MS
authors: Islas
authors: Centro de Química Inorgánica (CEQUINOR/CONICET, UNLP), Facultad de Ciencias Exactas, UNLP, C. Correo 962, 1900 La Plata, Argentina.
authors: Santiago T
authors: ST
authors: Ariza
authors: Centro de Química Inorgánica (CEQUINOR/CONICET, UNLP), Facultad de Ciencias Exactas, UNLP, C. Correo 962, 1900 La Plata, Argentina.
authors: Nadir
authors: N
authors: Jori
authors: Universidad Nacional del Chaco Austral, Cte. Fernández 755, 3700 Roque Sáenz Peña, Chaco, Argentina.
authors: Juan J
authors: JJ
authors: Martínez Medina
authors: Instituto de Investigación Biomedicina de Buenos Aires (IBioBA)-CONICET-Partner Institute of the Max Planck Society, Godoy Cruz 2390, C1425FQA Buenos Aires, Argentina.
authors: Martín J
authors: MJ
authors: Lavecchia
authors: Universidad Nacional del Chaco Austral, Cte. Fernández 755, 3700 Roque Sáenz Peña, Chaco, Argentina.
authors: Leonor L
authors: LL
authors: López Tévez
authors: Departamento de Química Inorgánica, Facultad de Ciencia y Tecnología, Universidad del País Vasco, Apdo 644, 48080 Bilbao, Spain.
authors: Luis
authors: L
authors: Lezama
authors: Departamento de Química Inorgánica, Facultad de Ciencia y Tecnología, Universidad del País Vasco, Apdo 644, 48080 Bilbao, Spain.
authors: Teófilo
authors: T
authors: Rojo
authors: Centro de Química Inorgánica (CEQUINOR/CONICET, UNLP), Facultad de Ciencias Exactas, UNLP, C. Correo 962, 1900 La Plata, Argentina.
authors: Patricia A M
authors: PA
authors: Williams
authors: Centro de Química Inorgánica (CEQUINOR/CONICET, UNLP), Facultad de Ciencias Exactas, UNLP, C. Correo 962, 1900 La Plata, Argentina. Electronic address: evelina@quimica.unlp.edu.ar.
authors: Evelina G
authors: EG
authors: Ferrer
mesh_terms: D000135:Acid Phosphatase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D013956:Antithyroid Agents / Q000737:chemistry / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy; D002417:Cattle; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D003300:Copper / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008713:Methimazole / Q000737:chemistry / Q000494:pharmacology*; D011487:Protein Conformation / Q000187:drug effects; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000935:Antifungal Agents; D013956:Antithyroid Agents; D056831:Coordination Complexes; D012710:Serum Albumin, Bovine; D008713:Methimazole; D003300:Copper; D000135:Acid Phosphatase
keywords: Anti-thyroid activity; Antifungal activity; BSA interactions; Copper(II); Methimazole; Phenanthroline