Curran, Robert J.
Silver (I) Complexes as Antimicrobial and Anticancer Drugs.
PhD thesis, National University of Ireland Maynooth.
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
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.
||Silver (I) Complexes; Antimicrobial and Anticancer Drugs;
||Faculty of Science and Engineering > Chemistry
||19 Nov 2010 11:44
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