In vitro and in vivo studies into the biological activities of 1,10-phenanthroline, 1,10-phenanthroline-5,6-dione and its copper(ii) and silver(i) complexes

Abstract

1,10-Phenanthroline ( phen, 5), 1,10-phenanthroline-5,6-dione ( phendione, 6), [Cu( phendione) 3 ]-(ClO 4 ) 2 ·4H 2 O (12) and [Ag( phendione) 2 ]ClO 4 (13) are highly active, in vitro, against a range of normal and cancerous mammalian cells, fungal and insect cell lines, with the metal complexes offering a clear enhancement in activity. Cytoselectivity was not observed between the tumorigenic and non-tumorigenic mammalian lines. In in vivo tests, using Galleria mellonella and Swiss mice, all four compounds were well tolerated in comparison to the clinical agent, cisplatin. In addition, blood samples taken from the Swiss mice showed that the levels of the hepatic enzymes, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), remained unaffected. Immunocompromised nude mice showed a much lower tolerance to 13 and, subsequently, when these mice were implanted with Hep-G2 (hepatic) and HCT-8 (colon) human-derived tumors, there was no influence on tumor growth.

Imidazole Schiff base ligands: Synthesis, coordination complexes and biological activities

“…[Ag(6)]ClO 4 was the least active across all of the microbial species, and the activities of the other water-insolubl e Ag(I) complexes were similar to that observed for water-soluble AgNO 3 . In these cases, activity against the fungal pathogen , C. albicans , was greater than that for bacterial pathogens, which is a trend similar to that previously reported for other Ag(I) complexes [5,6,16]. Although there was no clear discriminatory trends observed in activities between Gram-positive (S. aureus and MRSA) and Gram-negati ve (E. coli and P. aeruginosa ) bacteria, most of the complexes, and especially [Ag(4)]ClO 4 ÁMeOH, were more cytotoxic against P. aeruginosa .…”

Synthesis, characterisation and antimicrobial studies of organotin(IV) complexes with 1,10-phenanthroline derivatives

“…The only reagent to show good broad spectrum activity against all three bacteria was the dione ligand. This ligand has been previously shown by McCann and co-workers to be very active against several microbes, as well as the yeast Candida Albicans [12,15,16]. Furthermore, when they made silver(I) complexes with the dione ligand, they found that the activity against all the bacteria was increased.…”

“…The recent work of McCann and co-workers into the copper(II) and silver(I) complexes of 1,10-phenanthroline and 1,10-phenanthroline-5,6-dione have shown that they are active in vitro anticancer agents against selected cancer cell lines [12][13][14][15][16][17][18][19]. Our interest in the area of therapeutic agents, especially metal-based drugs, is fuelled by the search for new effective medicines for human health, particularly in the areas of cancer therapy and antimicrobials.…”

Re(I) tricarbonyl complex of 1,10-phenanthroline-5,6-dione: DNA binding, cytotoxicity, anti-inflammatory and anti-coagulant effects towards platelet activating factor

“…Recently, the anticancer activity of phendione and its Cu 2+ and Ag + complexes has been studied in a wide spectrum of cell lines, containing not only mouse's and monkeys' cells, but also human-derived cancer cell lines [23,24,26]. In the majority of cases, these complexes exhibit excellent biological activity and represent a class of DNA-targeting compounds capable of inhibiting nucleotide synthesis.…”

“…An interesting class of ligands is phenanthrolines and substituted derivatives which interact with DNA by aromatic π stacking between the base pairs, both when they are free or coordinated to a metal centre. Among the phenanthroline derivatives, 1,10-phenanthroline-5,6-dione (phendione), displays significant anticancer role with and without a coordinated metal [23,24], whereas it also displays antibacterial and antifungal activity [23][24][25][26][27].…”