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Silver (I) Complexes as Antimicrobial and Anticancer Drugs
Curran, Robert J.
This thesis describes the potential use of silver(I) complexes of 9- anthracenecarboxylic (9-acaH) and imidazoles as new antimicrobial and anticancer drugs. The detailed synthesis of silver(I)-containing carboxylates, such as polymeric [Ag2(9-aca)2]n and [Ag2(9-aca)2(DMSO)2]n, and the ammoniacontaining complex, [Ag4(9-aca)4(NH3)2], are provided along with imidazole derivatives, such as [Ag2(9-aca)2(DMSO)2]n and [Ag6(imidH)4(9-aca)6(MeOH)2]. Silver(I) carboxylates containing substituted imidazole ligands were also prepared and include the complex salts, [Ag(1-Me-imid)2]2[Ag4(9-aca)6] and [Ag(1-Bu-imid)2]2[Ag4(9-aca)6], along with [Ag2(1-Me-imid)2(9-aca)2], [Ag(2- Me-imidH)2(9-aca)], [Ag2(1-Bu-imid)2(9-aca)2], [Ag(apim)](9-aca)·H2O, [Ag(4- Ph-imidH)2(9-aca)] and [Ag2(2-Mebenz-imidH)4](9-aca)2. Polymeric silver(I) imidazolate complexes were made from 2-phenylimidazole, 4,5- dicyanoimidazole, benzimidazole and 2-methylbenzimidazole. All complexes were characterised by IR and NMR spectroscopy, microanalysis and, in many instances, by X-ray crystallography. The fluorescence properties of a selection of the complexes were also recorded. Complexes were screened, in vitro, for their antifungal (Candida albicans) and antibacterial activity (Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA)). Many of the new silver(I) complexes were more active than the prescription drugs currently used to treat microbial infections and cancerous tumours. For example, [Ag4(9-aca)4(NH3)2] was ca. 32 times more active than the prescription antifungal drug, Ketoconazole. This complex also exhibited high cytotoxicity towards bacterial cells, being ca. 9 times more active against both E. coli and MRSA than the known antibacterial agent, silver sulfadiazine. The hexanuclear imidazole complex, [Ag6(imidH)4(9-aca)6(MeOH)2], was the most active at inhibiting bacterial growth, being ca. 39 times better than silver sulfadiazine against E. coli. The in vivo cytotoxicity and antifungal characteristics of the silver(I) complexes was also examined using the insect model, Galleria mellonella. Healthy G. mellonella larvae appeared to be unaffected when treated with the silver(I) complexes at concentrations up to 100 μg cm-3. The silver(I) complexes also increased the survival rate of larvae administered with a lethal dose of C. albicans. Again, the ammonia-containing complex, [Ag4(9-aca)4(NH3)2], was the most effective at increasing the survival rate, greatly surpassing the efficacy of Ketoconazole. The silver(I) complexes were screened, in vitro, against a number of mammalian tumour cell lines (MCF-7, HT-29, Hep-G2 and A-498) and they all decreased cell proliferation. While most of the complexes were more active towards MCF-7 cells (breast cancer cells), [Ag(4-Ph-imidH)2(9-aca)] was equally cytotoxic against HT-29 cells (colon cancer cells). [Ag6(imidH)4(9-aca)6(MeOH)2], [Ag(1- Bu-imid)2]2[Ag4(9-aca)6], [Ag(1-Me-imid)2]2[Ag4(9-aca)6] and [Ag4(9- aca)4(NH3)2] were all ca. 7 times more active against breast cancer cells than the anthracene-containing anticancer drug, Mitoxantrone.
Keyword(s): Chemistry; Silver (I) Complexes; Antimicrobial and Anticancer Drugs
Publication Date:
Type: Doctoral thesis
Peer-Reviewed: No
Institution: Maynooth University
Citation(s): Curran, Robert J. (2009) Silver (I) Complexes as Antimicrobial and Anticancer Drugs. PhD thesis, National University of Ireland Maynooth.
File Format(s): application/pdf
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First Indexed: 2020-01-31 06:03:25 Last Updated: 2020-04-02 07:37:19