Diguanidino and "reversed" diamidino 2,3-diarylfurans as antimicrobial agents

Dicationic 2,5-bis(4-guanidinophenyl)furans 5a-5f, 2,5-bis [4-(arylimino)am inophenyl] 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-butylstan nyl] furan. Thermal melting studies with poly dA . dT and the duplex oligom er d(CGCGAATTCGCG)2 demonstrated high DNA binding affinities for a number o f the compounds. The binding affinities are highly dependent on structure a nd are significantly affected by substituents both on the phenyl rings of t he 2,5-diphenylfuran nucleus and on the cationic centers. Of the 17 novel d icationic compounds synthesized, six (6a, 6b, 5b, 6f, 6fi, 6i) exhibited MI Cs of 2 mug/mL or less versus Mycobacterium tuberculosis. Of the compounds screened against Candida albicans, three gave MICs of 2 mug/mL or less (5b, 6h, Si), and two (5b, 6i) were fungicidal, unlike a standard antifungal dr ug fluconazole, which was fungistatic. In addition, one of the tested compo unds (6i) exhibited a MIC of <1 mug/mL against Aspergillus fumigatus, while also being a fungicidal against this organism. Finally, when evaluated aga inst an expanded fungal panel, compound 6h showed good activity against Cry ptococcus neoformans and Rhizopus arrhizus.