Synthesis and biological activity of copper(II), silver(I) and gold(III) complexes with azoles as antifungal agents

[N. Lj. Stevanović]

[9], 141, [4] lista

U okviru ove doktorske disertacije, sintetisani su kompleksi bakra(II), srebra(I) i zlata(III) sa azolima koji se klinički koriste kao antifungalni agensi. U prvom delu doktorske disertacije opisani su antifungalni agensi koji se koriste u medicini za lečenje gljivičnih infekcija. Pored toga, dat je pregled kompleksa metala sa azolima kao potencijalnim terapeutskim agensima. U drugom delu disertacije, opisani su postupci za sintezu kompleksa bakra(II), srebra(I) i zlata(III) sa azolima (imidazol, 1-izopropilimidazol, 1-fenilimidazol, flukonazol, itrakonazol, mikonazol, klotrimazol, ekonazol, tiokonazol i vorikonazol) i metode za njihovu karakterizaciju i biološko ispitivanje. U delu disertacije koji se odnosi na Diskusiju rezultata, detaljno su prikazani rezultati spektroskopske i kristalografske karakterizacije sintetisanih kompleksa, rezultati dobijeni ispitivanjem njihove biološke aktivnosti (antimikrobne, antituberkulozne i antiproliferativne), kao i in vivo embriotoksičnost ovih kompleksa na modelu zebra ribica Danio rerio. Sintetisani kompleksi su okarakterisani primenom spektroskopskih (NMR, IR, i UV-Vis), elektrohemijskih (ciklična voltametrija) i kristalografskih metoda (difrakcija X-zraka sa monokristala), kao i primenom masene spektrometrije i merenjem molarne provodljivosti. Antimikrobna i antituberkulozna aktivnost sintetisanih kompleksa je poređena sa njihovom citotoksičnošću na zdravoj ćelijskoj liniji fibroblasta pluća (MRC-5). Kako bi se objasnila struktura kompleksa u rastvoru, korišćeni su DFT proračuni. Pored toga, u cilju definisanja mehanizma antimikrobnog delovanja kompleksa, ispitivane su njihove interakcije sa ct-DNA i BSA u odsustvu i prisustvu markera.

In this doctoral dissertation, copper(II), silver(I) and gold(III) complexes with antifungal azoles were synthesized. In the first part of this thesis, antifungal agents used in medicine for the treatment of fungal infections are described. In addition, metal complexes with azoles as potential therapeutic agents are reviewed. In the second part, procedures for the synthesis of copper(II), silver(I) and gold(III) complexes with azoles (imidazole, 1-isopropylimidazole, 1-phenylimidazole, fluconazole, itraconazole, miconazole, clotrimazole, econazole, tioconazole and voriconazole) and methods for their structural characterization and biological evaluation are given. In the part of the dissertation related to the Discussion of the obtained results, the spectroscopic and crystallographic characteristics of the synthesized complexes and the results obtained by evaluation of their biological activity (antimicrobial, antitubercular and antiproliferative) are presented in detail, as well as their embryotoxicity in the zebrafish model Danio rerio. The synthesized complexes with different azoles were structurally characterized by spectroscopic (NMR, IR, UV-Vis), electrochemical (cyclic voltammetry) and crystallographic methods (single-crystal X-ray diffraction analysis), mass spectrometry and molar conductivity measurements. The antimicrobial and antitubercular activities of the synthesized complexes were investigated and compared with their cytotoxicity on the healthy human lung fibroblast cell line (MRC-5). DFT calculations were used to explain the structure of the synthesized complexes in solution. To define the mechanism of antimicrobial action of the complexes, their interactions with ct-DNA and BSA in the absence and presence of site markers were studied.

546.562:547.78]-386(043.3) 546.571:547.78]-386(043.3) 546.593:547.78]-386(043.3)

Dvovalentni bakar - Kompleksna jedinjenja Jednovalentno srebro - Kompleksna jedinjenja Trovalentno zlato - Kompleksna jedinjenja

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