Diguanidino and “Reversed” Diamidino 2,5-Diarylfurans as Antimicrobial Agents

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 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.

Arylfurans as potential Trypanosoma cruzi trypanothione reductase inhibitors

“…(trimethylstannyl)furan 16 by reaction of furan with TMEDA and n-butyllithium and subsequent addition of trimethyltin chloride (Seitz et al 1983), and (2) palladium catalyzed coupling reaction between the distannane 16 and various arylhalides (Stille coupling) (Stephens et al 2001).…”

“…In view of these results, and aiming at the discovery of new trypanocidal compounds we evaluated the effect of the synthetic compounds 5-15 (Fig. 4) on TR and the whole trypomastigote and amastigote forms of the parasite.(trimethylstannyl)furan 16 by reaction of furan with TMEDA and n-butyllithium and subsequent addition of trimethyltin chloride (Seitz et al 1983), and (2) palladium catalyzed coupling reaction between the distannane 16 and various arylhalides (Stille coupling) (Stephens et al 2001).In vitro assay with T. cruzi TR -Recombinant T. cruzi TR was obtained as described by Borges et al (1995). The colorimetric microtitre plate assay was adapted from that described by Hamilton et al (2003).…”

“…Arylfurans present a broad-spectrum of biological activities [for example, antimicrobial activity (Stephens et al 2001, Lanteri et al 2004, effects against neurodegenerative, cardiovascular, and proliferative diseases (Lockhart et al 2004), inhibitory activity against the enzymes farnesyltransferase (Mitsch et al 2004) and PDE4 (Perrier et al 1999), vascularization inhibitor effect (Kuwano et al 1994)] and previous works (JockersScherübl et al 1989, Paulino et al 2002, Aguirre et al 2004 have shown that furan derivatives could be potential ligands for TR. In view of these results, and aiming at the discovery of new trypanocidal compounds we evaluated the effect of the synthetic compounds 5-15 (Fig.…”

Si̇stemi̇k Mantar Enfeksi̇yonlarinin Tedavi̇si̇nde Yeni̇ Hedefler Ve Yeni̇ Bi̇leşi̇kler: New Targets and New Compounds for the Treatment of Systemic Fungal Infections

“…Diğer bir çalışmada ise diguanido-2,5-difenilfuran türevlerinin (Şekil 5) DNA'ya bağlanma ilgileri, antifungal ve antimikobakteriyal etkileri oldukça iyi olarak bildirilmektedir (114). Halen bu alanda yoğun çalışmalar yürütülmekte olup yeni sordarin analogları arasında GM-191519, GM-211676, GM-222712, GM-237354 ve GR-135402 yer almaktadır (130)(131)(132) albicans'a karşı ketokonazol ile kıyaslanabilir bir etkiye sahip olduğunu bildirmişlerdir.…”

Novel linear triaryl guanidines, N-substituted guanidines and potential prodrugs as antiprotozoal agents

“…Structures with rigid frameworks of fused ring systems as linkers for the dicationic groups (e.g. carbazole, benzofuran, benzothiophene, 9H-fluorene, fluorenone, acridine and anthraquinone) were also reported as effective antimicrobial agents [22][23][24][25] and had high DNA minor groove binding affinity and postulated to involve water mediated interactions [26,27].…”