Synthesis and structure–antifungal activity Relationships of 3-Aryl-5-alkyl-2,5-dihydrofuran-2-ones and Their Carbanalogues: further refinement of tentative pharmacophore group

Pour, Milan; Špulák, Marcel; Balšánek, Vojtěch; Kuneš, Jiřı́; Kubanová, Petra; Buchta, Vladimı́r

doi:10.1016/s0968-0896(03)00220-7

Cited by 67 publications

(48 citation statements)

References 30 publications

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“…1B) with a 4-methoxyphenyl group at C-3 is significantly lower than those of the derivatives with a halogenated phenyl substitution (13). A recent paper (14) has also shown that the pharmacophoric element must include the five-membered lactone ring, as 3-(substituted aryl)cyclopent-2-enones were found to be completely inactive (Fig. 1C).…”

Section: Discussionmentioning

confidence: 85%

“…In agreement with these findings, our antifungal testing revealed that the racemic form of the natural product exhibited only a marginal effect (MIC Ͼ 32 g/ml) on our set of yeast and mold isolates (12). The preparation of synthetic derivatives with halogenated phenyl at C-3 and a methyl group at C-5 led to a significant increase of the in vitro antifungal effect, especially in filamentous fungi (12,13,14). The highest in vitro antifungal activity was linked to the substitution of the phenyl group at C-3 by halogens at positions 3 and 4 and to the presence of an acyloxymethyl group at C-5 (13).…”

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confidence: 99%

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In Vitro Activities of 3-(Halogenated Phenyl)-5-Acyloxymethyl- 2,5-Dihydrofuran-2-ones against Common and Emerging Yeasts and Molds

Buchta

Pour²,

Kubanová³

et al. 2004

Antimicrob Agents Chemother

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Three 3-(halogenated phenyl)-5-acyloxymethyl-2,5-dihydrofuran-2-ones were evaluated for activity against 191 strains of common and emerging yeasts and Aspergillus species by the broth microdilution test performed according to NCCLS guidelines. The furanone derivatives displayed broad-spectrum in vitro activity against potentially pathogenic yeasts and molds, especially Aspergillus spp. (MIC < 2.0 g/ml) and fluconazoleresistant yeast isolates, including Candida glabrata and Saccharomyces cerevisiae. The 4-bromophenyl derivative was the most effective derivative against the majority of species tested, except for the Candida tropicalis and C. glabrata strains, which were more susceptible to the 3-chlorophenyl derivative. The 3,4-dichlorophenyl derivative possessed a lesser in vitro antifungal effect. The potential of further experiments on animal infection and clinical studies is supported by the relatively low cytotoxicity and acute toxicity of the 4-bromophenyl compound. Thus, the halogenated 3-phenyl-5-acyloxymethyl derivatives of 2,5-dihydrofuran-2-one represent a novel, promising group of compounds with significant activity against relevant opportunistic fungi that are pathogenic to humans.The incidence of and mortality due to fungal infections have increased over the past few decades, particularly in the setting of immunocompromised hosts. In spite of the introduction of several new antifungal drugs, such as caspofungin and voriconazole, the therapeutic management of serious invasive mycoses still remains a challenge for pharmaceutical research and industry (11).3-(Halogenated phenyl)-5-acyloxymethyl-2,5-dihydrofuranones (Fig. 1A) represent a novel class of butenolide antimycotics based on (Ϫ)incrustoporin (the minus sign means that the compound is a levorotatory enantiomer), obtained from the extract of fermentation of the basidiomycete Incrustoporia carneola, as the lead structure. The natural product displays an antifungal effect toward phytopathogenic molds and some cytotoxic activity ( Fig. 1) (15). In agreement with these findings, our antifungal testing revealed that the racemic form of the natural product exhibited only a marginal effect (MIC Ͼ 32 g/ml) on our set of yeast and mold isolates (12). The preparation of synthetic derivatives with halogenated phenyl at C-3 and a methyl group at C-5 led to a significant increase of the in vitro antifungal effect, especially in filamentous fungi (12,13,14). The highest in vitro antifungal activity was linked to the substitution of the phenyl group at C-3 by halogens at positions 3 and 4 and to the presence of an acyloxymethyl group at C-5 (13). The conversion of 5-hydroxymethyl derivatives into esters resulted in a broader spectrum of activity and in MICs below 4 g/ml for most yeasts and molds tested. Interestingly, the effect was not stereospecific, i.e., there were no significant differences in the MICs of the enantiomers and the racemate (13).Based on these experiments, we decided to investigate the in vitro profile of the most promising three esters (LNO6...

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Section: Discussionmentioning

confidence: 85%

mentioning

confidence: 99%

In Vitro Activities of 3-(Halogenated Phenyl)-5-Acyloxymethyl- 2,5-Dihydrofuran-2-ones against Common and Emerging Yeasts and Molds

Buchta

Pour²,

Kubanová³

et al. 2004

Antimicrob Agents Chemother

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“…In particular, compounds bearing the 2-furanone backbone have exhibited diverse biological activities, such as antiprotozoal, antibacterial (including inhibition of biofilm formation), antimycobacterial, antitumoral, antifungal, and cyclooxygenase-2 inhibition (8)(9)(10)(11)(12)(13)(14). The efficacy of several butyrolactone derivatives against mycobacteria suggests that these structures be a new template for tuberculosis drug development (14,15).…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis, andIn vitroantituberculosis activity of 2(5H)-Furanone derivatives

Ngwane

Panayides²,

Chouteau

et al. 2016

IUBMB Life

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A series of 2(5H)-furanone-based compounds were synthesized from commercially available mucohalic acids. From the first-generation compounds, three showed inhibitory activity (10 mg/mL) of at least 35% against Mycobacterium smegmatis mc 2 155 growth (Bioscreen C system). In screening the active first-generation compounds for growth inhibition against Mycobacterium tuberculosis H37Rv, the most active compound was identified with a minimum inhibitory concentration (MIC 99 ) of 8.07 mg/mL (15.8 mM) using BACTEC 460 system. No cross-resistance was observed with some current first-line anti-TB drugs, since it similarly inhibited the growth of multidrug resistant (MDR) clinical isolates. The compound showed a good selectivity for mycobacteria since it did not inhibit the growth of selected Gram-positive and Gram-negative bacteria. It also showed synergistic activity with rifampicin (RIF) and additive activity with isoniazid (INH) and ethambutol (EMB). Additional time-kill studies showed that the compound is bacteriostatic to mycobacteria, but cytotoxic to the Chinese Additional Supporting Information may be found in the online version of this article. 612 IUBMB LifeHamster Ovarian (CHO) cell line. From a second generation library, two compounds showed improved anti-TB activity against M. tuberculosis H37Rv and decreased CHO cell cytotoxicity. The compounds exhibited MIC values of 2.62 mg/mL (5.6 mM) and 3.07 mg/mL (5.6 mM) respectively. The improved cytotoxicity against CHO cell line of the two compounds ranged from IC 50 5 38.24 mg/mL to IC 50 5 45.58 mg/mL when compared to the most active first-generation compound (IC 50 5 1.82 mg/mL). The two second generation leads with selectivity indices (SI) of 14.64 and 14.85 respectively, warrant further development as anti-TB drug candidates. V C 2016 IUBMB Life, 68(8):612-620, 2016

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“…1). Furan-2(5H)-ones are attractive targets in organic and medicinal chemistry owing to their potency and wide spectrum of biological activities including antifungal [5], anti-inflammatory [6], antitumor [(? )-bullatacin possesses notable levels of cytotoxicity against many human tumor cell lines] [7], and antibacterial (inhibitory activity against Escherichia coli) [8].…”

Section: Introductionmentioning

confidence: 99%

SnO nanoparticles: a robust and reusable heterogeneous catalyst for the synthesis of 3,4,5-substituted furan-2(5H)-ones

Safaei‐Ghomi

Heidari-Baghbahadorani

Shahbazi‐Alavi

2014

Monatsh Chem

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SnO nanoparticles as an efficient and recyclable catalyst have been successfully prepared and were used as a heterogeneous catalyst for the one-pot synthesis of 3,4,5-substituted furan-2(5H)-ones by the three-component reaction of aniline derivatives, dialkyl acetylene dicarboxylate, and aromatic aldehydes in ethanolic medium at room temperature. This work consistently has the advantages of excellent yields, short reaction time, simple workup, and recyclability of the catalyst up to six runs without appreciable loss of activity.

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Synthesis and structure–antifungal activity Relationships of 3-Aryl-5-alkyl-2,5-dihydrofuran-2-ones and Their Carbanalogues: further refinement of tentative pharmacophore group

Cited by 67 publications

References 30 publications

In Vitro Activities of 3-(Halogenated Phenyl)-5-Acyloxymethyl- 2,5-Dihydrofuran-2-ones against Common and Emerging Yeasts and Molds

In Vitro Activities of 3-(Halogenated Phenyl)-5-Acyloxymethyl- 2,5-Dihydrofuran-2-ones against Common and Emerging Yeasts and Molds

Design, synthesis, andIn vitroantituberculosis activity of 2(5H)-Furanone derivatives

SnO nanoparticles: a robust and reusable heterogeneous catalyst for the synthesis of 3,4,5-substituted furan-2(5H)-ones

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