Structure and antimicrobial activity of silver(I) complexes with some clinically used azoles

[M. Stanković]

[5], 107, [3] listova

Predmet ove doktorske disertacije obuhvata sintezu, karakterizaciju i ispitivanje antimikrobne i citotoksične aktivnosti osam novih kompleksa srebra(I) sa azolima koji se koriste za lečenje gljivičnih infekcija (klotrimazol, ekonazol i vorikonazol). Za karakterizaciju sintetisanih kompleksa korišćene su NMR, IR i UVVis cpektroskopske metode, masena spektrometrija i ciklična voltametrija. Sastav i čistoća kompleksa su potvrđeni primenom elementalne mikroanalize, dok je kristalna struktura određena metodom rendgenske strukturne analize. Kvantno-mehanički proračuni su korišćeni u cilju utvrđivanja termodinamički najpovoljnije strukture kompleksa u rastvoru. Ispitivana je aktivnost sintetisanih kompleksa srebra(I) prema različitim bakterijskim i gljivičnim sojevima, pri čemu su utvrđene minimalne inhibitorne koncentracije (MIC) u opsegu od 0,01 – 49,2 μM, dok je citotoksični potencijal određen na zdravoj ćelijskoj liniji fibroblasta pluća, sa IC50 vrednostima od 10 – 36,1 µM. Pored toga, ispitivana je i sposobnost inhibicije formiranja biofilmova, pri čemu je zabeleženo smanjenje formiranja biofilma od 77 do 90%. U Opštem delu disertacije prikazan je pregled lekova koji se koriste u terapiji gljivičnih infekcija, uz poseban osvrt na pojavu i rast rezistentnosti mikroorganizama na konvencionalne antigljivične lekove. Akcenat je stavljen i na značaj kompleksnih jedinjenja u medicini sa fokusom na antimikrobna svojstva kompleksa srebra(I). Drugi deo disertacije obuhvata metodologiju sinteze kompleksa srebra(I) sa azolima i metode spektroskopske, kristalografske i biološke analize. Završni deo disertacije posvećen je diskusiji rezultata, uključujući interpretaciju spektroskopskih i kristalografskih podataka, kao i procenu antimikrobne i citotoksične aktivnosti sintetisanih jedinjenja i rezultata teorijskih proračuna.

The subject of this doctoral dissertation is related to the synthesis, characterization, and evaluation of the antimicrobial and cytotoxic activities of eight new silver(I) complexes with azoles used in the treatment of fungal infections (clotrimazole, econazole, and voriconazole). The synthesized complexes were characterized using NMR, IR, and UV-Vis spectroscopic methods, mass spectrometry, and cyclic voltammetry. The composition and purity of the complexes were confirmed by elemental microanalysis, while their crystal structures were determined by single crystal X-ray diffraction analysis. Quantum-mechanical calculations were employed to determine the thermodynamically favorable structures of the complexes in solution. The activity of the synthesized silver(I) complexes was tested against various bacterial and fungal species, with minimum inhibitory concentration (MIC) values ranging from 0.01 to 49.2 μM. The cytotoxic potential was assessed on a healthy human lung fibroblast cell line, yielding IC50 values in the range of 10 – 36.1 µM. In addition, the ability of the complexes to inhibit biofilm formation was investigated, revealing a reduction in biofilm formation of 77 – 90%. The Introductory section of the dissertation provides an overview of antifungal drugs currently used in therapy, with particular emphasis on the emergence and increasing resistance of microorganisms to conventional antifungal agents. Special attention is also given to the importance of coordination compounds in medicine, focusing on the antimicrobial propreties of silver(I) complexes. The second part of the dissertation describes the syntetics procedures for the preparation of silver(I)-azole complexes, as well as the spectroscopic, crystallographic and biological methods applied for their characterization. The final section of the dissertation is devoted to the discussion of the results, including the interpretation of spectroscopic and crystallographic data, as well as the evaluation of antifmicrobial and cytotoxic activities and theoretical calculations.

546.571-386(043.3)

Srebro, jednovalentno - Antimikrobna aktivnost - Citotoksična aktivnost

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