Diguanidino and "reversed" diamidino 2,5-diarylfurans as antimicrobial agents.
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 microg/mL or less versus Mycobacterium tuberculosis. Of the compounds screened against Candida albicans, three gave MICs of 2 microg/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 <1 microg/mL against 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.
Stephens
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CE
Department of Chemistry, Georgia State University, 1 University Plaza, Atlanta, Georgia 30303-3083, USA.
Tanious
F
F
Kim
S
S
Wilson
W D
WD
Schell
W A
WA
Perfect
J R
JR
Franzblau
S G
SG
Boykin
D W
DW
D000578:Amidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000631:Aminopyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004247:DNA / Q000737:chemistry; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D013329:Structure-Activity Relationship
C427736:2,5-bis(2-methoxy-4-(2-pyridylimino)aminophenyl)furan; C427735:2,5-bis(2-methyl-4-(5-methyl-2-pyridyimino)aminophenyl)furan; D000578:Amidines; D000631:Aminopyridines; D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D005663:Furans; D004247:DNA