Diguanidino and "Reversed" Diamidino 2,5-Diarylfurans as Antimicrobial Agents
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- 作者：Chad E. Stephens ; Farial Tanious ; Susan Kim ; W. David Wilson ; Wiley A. Schell ; John R. Perfect ; Scott G. Franzblau ; and David W. Boykin
- 刊名：Journal of Medicinal Chemistry
- 出版年：2001
- 出版时间：May 24, 2001
- 年：2001
- 卷：44
- 期：11
- 页码：1741 - 1748
- 全文大小：89K
- 年卷期：v.44,no.11(May 24, 2001)
- ISSN：1520-4804
文摘
Dicationic 2,5-bis(4-guanidinophenyl)furans 5a-5f, 2,5-bis[4-(arylimino)aminophenyl]furans6a-6b and 6e-6k, and 2,5-bis[4-(alkylimino)aminophenyl]furans 6c-6d have been synthesizedstarting from 2,5-bis[tri-n-butylstannyl]furan. Thermal melting studies with poly dA
dT andthe duplex oligomer d(CGCGAATTCGCG)2 demonstrated high DNA binding affinities for anumber of the compounds. The binding affinities are highly dependent on structure and aresignificantly affected by substituents both on the phenyl rings of the 2,5-diphenylfuran nucleusand on the cationic centers. Of the 17 novel dicationic compounds synthesized, six (6a, 6b, 5b,6f, 6h, 6i) exhibited MICs of 2 
r.gif">g/mL or less versus Mycobacterium tuberculosis. Of thecompounds screened against Candida albicans, three gave MICs of 2 r.gif">g/mL or less (5b, 6h,6i), and two (5b, 6i) were fungicidal, unlike a standard antifungal drug fluconazole, whichwas fungistatic. In addition, one of the tested compounds (6i) exhibited a MIC of <1 r.gif">g/mLagainst Aspergillus fumigatus, while also being a fungicidal against this organism. Finally,when evaluated against an expanded fungal panel, compound 6h showed good activity againstCryptococcus neoformans and Rhizopus arrhizus.
dT andthe duplex oligomer d(CGCGAATTCGCG)2 demonstrated high DNA binding affinities for anumber of the compounds. The binding affinities are highly dependent on structure and aresignificantly affected by substituents both on the phenyl rings of the 2,5-diphenylfuran nucleusand on the cationic centers. Of the 17 novel dicationic compounds synthesized, six (6a, 6b, 5b,6f, 6h, 6i) exhibited MICs of 2 r.gif">g/mL or less versus Mycobacterium tuberculosis. Of thecompounds screened against Candida albicans, three gave MICs of 2 r.gif">g/mL or less (5b, 6h,6i), and two (5b, 6i) were fungicidal, unlike a standard antifungal drug fluconazole, whichwas fungistatic. In addition, one of the tested compounds (6i) exhibited a MIC of <1 r.gif">g/mLagainst Aspergillus fumigatus, while also being a fungicidal against this organism. Finally,when evaluated against an expanded fungal panel, compound 6h showed good activity againstCryptococcus neoformans and Rhizopus arrhizus.