Diguanidino and "reversed" diamidino 2,5-diarylfurans as antimicrobial agents

C. E. Stephens, F. Tanious, S. Kim, W. D. Wilson, W. A. Schell, J. R. Perfect, S. G. Franzblau, D. W. Boykin

Research output: Contribution to journalArticle

131 Citations (Scopus)

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 <1 μg/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.

Original languageEnglish (US)
Pages (from-to)1741-1748
Number of pages8
JournalJournal of Medicinal Chemistry
Volume44
Issue number11
DOIs
StatePublished - May 24 2001
Externally publishedYes

Fingerprint

Furans
Anti-Infective Agents
Rhizopus
Cryptococcus neoformans
Aspergillus fumigatus
Fluconazole
Candida albicans
Mycobacterium tuberculosis
Freezing
Hot Temperature
DNA
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Stephens, C. E., Tanious, F., Kim, S., Wilson, W. D., Schell, W. A., Perfect, J. R., ... Boykin, D. W. (2001). Diguanidino and "reversed" diamidino 2,5-diarylfurans as antimicrobial agents. Journal of Medicinal Chemistry, 44(11), 1741-1748. https://doi.org/10.1021/jm000413a

Diguanidino and "reversed" diamidino 2,5-diarylfurans as antimicrobial agents. / Stephens, C. E.; Tanious, F.; Kim, S.; Wilson, W. D.; Schell, W. A.; Perfect, J. R.; Franzblau, S. G.; Boykin, D. W.

In: Journal of Medicinal Chemistry, Vol. 44, No. 11, 24.05.2001, p. 1741-1748.

Research output: Contribution to journalArticle

Stephens, CE, Tanious, F, Kim, S, Wilson, WD, Schell, WA, Perfect, JR, Franzblau, SG & Boykin, DW 2001, 'Diguanidino and "reversed" diamidino 2,5-diarylfurans as antimicrobial agents', Journal of Medicinal Chemistry, vol. 44, no. 11, pp. 1741-1748. https://doi.org/10.1021/jm000413a
Stephens, C. E. ; Tanious, F. ; Kim, S. ; Wilson, W. D. ; Schell, W. A. ; Perfect, J. R. ; Franzblau, S. G. ; Boykin, D. W. / Diguanidino and "reversed" diamidino 2,5-diarylfurans as antimicrobial agents. In: Journal of Medicinal Chemistry. 2001 ; Vol. 44, No. 11. pp. 1741-1748.
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