Antifungal and antibacterial activities of diarylamidine derivatives

Abstract

The antifungal and antibacterial properties of a series of 70 diarylamidine derivatives were evaluated. Several of these compounds exhibited considerable antimicrobial potency. A survey of the structure-activity relationship demonstrated that minor structural variations resulted in significant changes of antimicrobial activity. In general, the structural features required for antifungal activity coincided with those required for antibacterial activity. Both the antifungal and the antibacterial properties of the diarylamidines depended on the presence and the positions, of both amidino groups, on the nature of the central bridge connecting the two aryl moieties, and on the nature of these aryl residues (preferably indole). The most active compound was evaluated for its activity against Candida albicans infection in mice.

Novel Broad-Spectrum Bis-(Imidazolinylindole) Derivatives with Potent Antibacterial Activities against Antibiotic-Resistant Strains

“…This class of compounds has been evaluated previously for antimicrobial properties (2), as well as for antiproteolytic, anticoagulant (23), and antiproliferative activity (5). In our study, four bis-(imidazolinylindole) compounds from the diarylamidine library exhibited very potent activity in the macrophage rescue screen.…”

A Resistance Determinant to Nucleic Acid-Binding Compounds in Methicillin-Resistant Staphylococcus Aureus

“…the determinant bind to a variety of anionic compounds including nucleic acids, mast-cell heparin and mucopolysaccharides. Bis(guany1hydrazones) (Denny and Cain, 1979), quaternary ammonium compounds (Scott, 1962) and diamidine compounds such as propamidine and amicarbalide (Anne et al, 1980) bind to nucleic acids, and the DNA-intercalating properties of ethidium bromide (Cain et al, 1978) and the acridines (Wolfe et al, 1972) have been well documented. This common property of binding to nucleic acids has prompted us to refer to the determinant encoding resistance to these compounds as the NAB (nucleic acid-binding compounds)-resistance determinant.…”

Dicationic DNA Minor Groove Binders as Antimicrobial Agents

“…16 Because the length of these target molecules varies significantly it was necessary to compare the DNA binding of these molecules to oligomers of varying AT-tracts. Table 16.9 contains comparisons of DT m values for furamidine (17) and its three extended analogs 29-31 with three different oligomers with 4,6-and 8-AT base pair binding sites. Subsequently, 29 has been found to bind to DNA in an unusual dimer motif which has potential for development of a new gene-regulation paradigm [144][145][146].…”

“…However, on oral administration of pentamidine dioxime in the immunosuppressed rat model for PCP it was only moderately effective [106]. We have reported that the bisamidoxime and bis-O-methylamidoxime of furamidine (17) were quite effective anti-PCP agents in the rat model on both oral and intravenous administration (see Tab. 16.13) [108]. However, the bis-O-ethylamidoxime of 17 was ineffective, demonstrating a remarkable sensitivity to structure.…”