Extended Aromatic Furan Amidino Derivatives as Anti-<i>Pneumocystis carinii</i> Agents

Kt, Hopkins; Wilson, W. David; Bc, Bender; Dr, McCurdy; Hall, J. E.; Tidwell, R. R.; Kumar, Arvind; Bajić, Miroslav; Dw, Boykin

doi:10.1021/jm980230c

Cited by 182 publications

(81 citation statements)

References 29 publications

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“…1 bind to the AATT sequence in oligo1 as classical minor-groove monomer complexes. The results, where comparable, are equivalent to those in the literature (4,5,23,24) and indicate that the oligomer hairpin models and surface attachment in SPR experiments do not strongly affect the compound-DNA complexes. The agreement between footprinting and SPR results for relative binding of DB293 and DB270 also supports use of the hairpin model systems.…”

Section: Discussionsupporting

confidence: 86%

“…O rganic cations that bind in the DNA minor groove have biological activities that range from anti-opportunistic infection to anticancer properties (1)(2)(3)(4)(5). Such compounds have also provided a wealth of fundamental information about nucleic acid recognition properties, and they continue to be important models in the study of nucleic acid complexes (1,2,(6)(7)(8).…”

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confidence: 99%

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Specific molecular recognition of mixed nucleic acid sequences: An aromatic dication that binds in the DNA minor groove as a dimer

Wang

Bailly

Kumar

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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124

109

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Phenylamidine cationic groups linked by a furan ring (furamidine) and related compounds bind as monomers to AT sequences of DNA. An unsymmetric derivative (DB293) with one of the phenyl rings of furamidine replaced with a benzimidazole has been found by quantitative footprinting analyses to bind to GC-containing sites on DNA more strongly than to pure AT sequences. NMR structural analysis and surface plasmon resonance binding results clearly demonstrate that DB293 binds in the minor groove at specific GC-containing sequences of DNA in a highly cooperative manner as a stacked dimer. Neither the symmetric bisphenyl nor bisbenzimidazole analogs of DB293 bind significantly to the GC containing sequences. DB293 provides a paradigm for design of compounds for specific recognition of mixed DNA sequences and extends the boundaries for small molecule-DNA recognition. O rganic cations that bind in the DNA minor groove have biological activities that range from anti-opportunistic infection to anticancer properties (1-5). Such compounds have also provided a wealth of fundamental information about nucleic acid recognition properties, and they continue to be important models in the study of nucleic acid complexes (1, 2, 6-8). Netropsin ( Fig. 1) was the first minor-groove-binding compound crystallized with a B-form DNA, and the structure of the complex provided clear suggestions about the molecular basis for AT base pair sequence-specific recognition (9). The structure also lead to proposals by the Dickerson and Lown groups for minor-groove binding netropsin analogs, lexitropsins, that could specifically recognize GC base pairs and could, thus, have extended sequence recognition capability (10-12). Initial efforts in the design of analogs of netropsin that could recognize GC base pairs, however, yielded compounds of limited specificity. A breakthrough in this area occurred with the discovery that the monocationic relative of netropsin, distamycin ( Fig. 1), could bind into the minor groove of some AT sequences of DNA as a stacked, antiparallel dimer (7,13,14). Replacement of pyrrole groups in distamycin by imidazole provided lexitropsins with improved GC recognition specificity through dimer complexes, and current design efforts in the pyrrole-imidazole polyamide system have reached a high level of success (15-18). With recent developments by the Dervan group, AT and TA as well as GC and CG base pairs can now be effectively distinguished in DNA sequences by polyamides (15-18).Interestingly, the polyamide system is the only one of the well known minor-groove binding motifs that has yielded conclusive evidence for formation of the stacked-dimer recognition unit, although recent evidence indicates that some monocationic cyanine dyes can form an array of stacked dimers in the DNA minor groove (19). No dications have been found to form the stacked-dimer recognition motif. Netropsin, the first minorgroove-binding agent to be characterized in detail and a dicationic relative of the monocation distamycin (Fig. 1), for example, does n...

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Section: Discussionsupporting

confidence: 86%

mentioning

confidence: 99%

Specific molecular recognition of mixed nucleic acid sequences: An aromatic dication that binds in the DNA minor groove as a dimer

Wang

Bailly

Kumar

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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124

109

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“…45 In each case the key step of benzimidazole ring formation is achieved by oxidative coupling of an aldehyde with a phenylenediamine. For the synthesis of 4 the bis-nitrile was first prepared and then it was converted into the bis-amidine by Pinner methodology.…”

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confidence: 99%

Antimicrobial activity of the DNA minor groove binders furamidine and analogs

Boykin¹

2002

J. Braz. Chem. Soc.

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Análogos arílicos de diamidinas da pentamidina e do berenil que interagem com a fenda menor de DNA estão sendo sintetizados com amplo espectro de atividade antimicrobiana. Várias séries de análogos da furamidina, 1,5-bis[4-amidinofenil]furano foram descritas e apresentaram boa potência quando administradas de forma intravenosa. Entretanto, elas foram inativas quando administradas oralmente. As pró-drogas do tipo amidoxima e carbamato dessas furamidinas são potentes quando administradas oralmente. Atualmente uma dessas pró-drogas, a bis-O-metiloxima está em estudos clínicos de Fase II.Aryl diamidine analogs of pentamidine and berenil that bind to the minor groove of DNA have been developed which show broad spectrum antimicrobial activity. Several series of analogs of 2,5-bis[4-amidinophenyl]furan (furamidine) have been described which are quite effective when given intravenously, however they are ineffective on oral administration. Amidoxime and carbamate prodrugs of furamidine are quite effective when given orally. One of these prodrugs, a bis-O-methylamidoxime is currently in Phase II clinical trials.

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“…Its applications (Fig. 6) as an intermediate for the synthesis of pharmaceuticals [84], antifungal agent [85], macrocyclic ligand [86,87], and organic conductor [88] have been described. DFF is also used as an important monomer for furan based polymers.…”

Section: Catalytic Oxidation Of Hmf To Dffmentioning

confidence: 99%

Advances in selective catalytic transformation of ployols to value-added chemicals

Wang

et al. 2013

Chinese Journal of Catalysis

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Extended Aromatic Furan Amidino Derivatives as Anti-Pneumocystis carinii Agents

Cited by 182 publications

References 29 publications

Specific molecular recognition of mixed nucleic acid sequences: An aromatic dication that binds in the DNA minor groove as a dimer

Specific molecular recognition of mixed nucleic acid sequences: An aromatic dication that binds in the DNA minor groove as a dimer

Antimicrobial activity of the DNA minor groove binders furamidine and analogs

Advances in selective catalytic transformation of ployols to value-added chemicals

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