Diguanidino and “Reversed” Diamidino 2,5-Diarylfurans as Antimicrobial Agents

Abstract

Dicationic 2,5-bis(4-guanidinophenyl)furans 5a − 5f, 2,5-bis[4-(arylimino)aminophenyl]furans 6a − 6b and 6e − 6k, and 2,5-bis[4-(alkylimino)aminophenyl]furans 6c − 6d have been synthesized starting from 2,5-bis[tri-n-butylstannyl]furan. Thermal melting studies with poly dA•dT and the duplex oligomer d(CGCGAATTCGCG)₂ demonstrated high DNA binding affinities for a number of the compounds. The binding affinities are highly dependent on structure and are significantly affected by substituents both on the phenyl rings of the 2,5-diphenylfuran nucleus and on the cationic centers. Of the 17 novel dicationic compounds synthesized, six (6a, 6b, 5b, 6f, 6h, 6i) exhibited MICs of 2 μg/mL or less versus Mycobacterium tuberculosis. Of the compounds screened against Candida albicans, three gave MICs of 2 μg/mL or less (5b, 6h, 6i), and two (5b, 6i) were fungicidal, unlike a standard antifungal drug fluconazole, which was fungistatic. In addition, one of the tested compounds (6i) exhibited a MIC of Aspergillus fumigatus, while also being a fungicidal against this organism. Finally, when evaluated against an expanded fungal panel, compound 6h showed good activity against Cryptococcus neoformans and Rhizopus arrhizus.