Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 44, Issue 11, Pages 1741-1748Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm000413a
Keywords
-
Categories
Funding
- NIAID NIH HHS [R01AI 46365-01A2] Funding Source: Medline
- PHS HHS [R01GN61587] Funding Source: Medline
Ask authors/readers for more resources
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, 6fi, 6i) exhibited MICs 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 drug fluconazole, which was fungistatic. In addition, one of the tested compounds (6i) exhibited a MIC of <1 mug/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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available