Antifungal promising agents of zinc(II) and copper(II) derivatives based on azole drug

Author(s):Show less -

de Azevedo-Franca, Jose Aleixo ^[1] ; Borba-Santos, Luana Pereira ^[2] ; Pimentel, Giovana de Almeida ^[1] ; Franco, Chris Hebert Jesus ^[1] ; Souza, Cassiano ^[1] ; Celestino, Jaqueline de Almeida ^[1] ; de Menezes, Emanuella Figueiredo ^[2] ; dos Santos, Nathalia Pinheiro ^[2] ; Vieira, Eduardo Guimaraes ^[3] ; Ferreira, Ana Maria Da Costa ^[3] ; de Souza, Wanderley ^{[4, 5]} ; Rozental, Sonia ^[2] ; Navarro, Maribel ^{[6, 1]}

Affiliation

^[1] Univ Fed Juiz de Fora, Lab Quim Bioinorgan & Catalise, Dept Quim, ICE, Juiz De Fora, MG - Brazil

^[2] Univ Fed Juiz de Fora, Lab Biol Celular Fungos, Inst Biofis Carlos Chagas Filho, Juiz De Fora, MG - Brazil

^[3] Univ Sao Paulo, Inst Quim, Lab Bioinorgan Catalise & Farmacol, S ao Paulo, SP - Brazil

^[4] Univ Fed Rio de Janeiro, Lab Ultraestrutura Celular Hertha Meyer, Inst Biofis Carlos Chagas Filho, Inst Nacl Ciencia & Tecnol INBEB, Rio De Janeiro - Brazil

^[5] Univ Fed Rio de Janeiro, Ctr Nacl Biol Estrutural & Bioimagens, Rio De Janeiro - Brazil

^[6] INMETRO, Inst Nacl Metrol Qualidade & Tecnol, Xerem, RJ - Brazil

• Document type: Journal article
• Source: Journal of Inorganic Biochemistry; v. 219, JUN 2021.
• Web of Science Citations: 2

Abstract

A series of new metal complexes, {[}Zn(KTZ)2(Ac)2].H2O (1), {[}Zn(KTZ)2Cl2].0.4CH3OH (2), {[}Zn(KTZ)2(H2O) (NO3)](NO3) (3), {[}Cu(KTZ)2(Ac)2].H2O (4), {[}Cu(KTZ)2Cl2].3.2H2O (5), {[}Cu(KTZ)2(H2O)(NO3)](NO3).H2O (6), were synthesized by a reaction of ketoconazole (KTZ) with their respective zinc or copper salts under mild conditions. Similarly, six corresponding metal-CTZ (clotrimazole) complexes {[}Zn(CTZ)2(Ac)2].4H2O (7), {[}Zn (CTZ)2Cl2] (8), {[}Zn(CTZ)2(H2O)(NO3)](NO3).4H2O (9), {[}Cu(CTZ)2(Ac)2].H2O (10), {[}Cu(CTZ)2Cl2].2H2O (11), {[}Cu(CTZ)2(H2O)(NO3)](NO3).2H2O (12), were obtained. These metal complexes were characterized by elemental analyses, molar conductivity, 1H and 13C[1H] nuclear magnetic resonance, UV/Vis, and infrared spectroscopies. Further, the crystal structure for complexes 7 and 10 was determined by single-crystal X-ray diffraction. The antifungal activity of these metal complexes was evaluated against three fungal species of medical relevance: Candida albicans, Cryptococcus neoformans, and Sporothrix brasiliensis. Complexes 1 and 3 exhibited the greatest antifungal activity with a broad spectrum of action at low concentrations and high selectivity. Some morphological changes induced by these metal complexes in S. brasiliensis cells included yeasthyphae conversion, an increase in cell size and cell wall damage. The strategy of coordination of clinic drugs (KTZ and CTZ) to zinc and copper was successful, since the corresponding metal complexes were more effective than the parent drug. Particularly, the promising antifungal activities displayed by Zn-KTZ complexes make them potential candidates for the development of an alternative drug to treat mycoses. (AU)

• FAPESP's process: 16/16735-8 - Imobilization of potential metallopharmaceuticals in inorganic and organic matrices for modified delivery
• Grantee: Eduardo Guimarães Vieira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
• Grantee: Ohara Augusto
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC