The relative and absolute stereochemistry of the antifungal agent preussin.

Johnson, Janice H.; Phillipson, Douglas W.; Kahle, A. D.

doi:10.7164/antibiotics.42.1184

Cited by 72 publications

(44 citation statements)

References 2 publications

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“…as a broad-spectrum antifungal agent active against both yeast and filamentous fungi (22,23,38), has potent growth-inhibitory and apoptosis-inducing effects on human cancer cells. Preussin is structurally related to the protein synthesis inhibitor anisomycin (22,38) (Fig. 1), but its relatively weak effect on translation, seen in the present study, suggests that the crucial target of preussin is different.…”

mentioning

confidence: 99%

Inhibition of Cyclin-Dependent Kinase Activity and Induction of Apoptosis by Preussin in Human Tumor Cells

Achenbach¹,

Slater²,

Brummerhop

et al. 2000

Antimicrob Agents Chemother

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In this paper, we report that (؉)-preussin, a pyrrolidinol alkaloid originally identified as an antifungal agent, has growth-inhibitory and cytotoxic effects on human cancer cells. Preussin was found to be a potent inhibitor of cyclin E kinase (CDK2-cyclin E) in vitro (50% inhibitory concentration; ϳ500 nM) and to inhibit cell cycle progression into S phase. In agreement with these findings, the level of the cyclin-dependent kinase inhibitor p27 KIP-1 is increased in response to preussin treatment while the expression of both cyclin A and the transcription factor E2F-1 is down-regulated. Preussin also induces programmed cell death (apoptosis), which requires caspase activation and involves the release of cytochrome c from mitochondria. This induction of apoptosis is not blocked by high levels of Bcl-2, which usually confers resistance to chemotherapeutic agents. Taken together, our data indicate that preussin could be a promising lead compound for the development of a new class of potent antitumor drugs.

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mentioning

confidence: 99%

Inhibition of Cyclin-Dependent Kinase Activity and Induction of Apoptosis by Preussin in Human Tumor Cells

Achenbach¹,

Slater²,

Brummerhop

et al. 2000

Antimicrob Agents Chemother

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“…The structures of palmitic acid, clionasterol [ 22 ], ergosterol 5,8-endoperoxides [ 14 ], chrysophanic acid ( 1a ) [ 13 ], emodin ( 1b ) [ 14 ], asterriquinol D dimethyl ether ( 2a ) [ 15 ], petromurin C ( 2b ) [ 16 ], kumbicin B ( 2c ) [ 15 ], kumbicin A ( 2d ) [ 15 ], 2″-oxoasterriquinol D methyl ether ( 3 ) [ 17 ], kumbicin D ( 4 ) [ 15 ], preussin ( 5a ) [ 18 , 19 , 20 ], (3 S , 6 S )-3,6-dibenzylpiperazine-2,5-dione ( 6 ) [ 21 ] and 4-(acetylamino) benzoic acid ( 7 ) [ 22 ] were elucidated by analysis of their 1D and 2D NMR spectra as well as HRMS data, and also by comparison of their spectral data to those reported in the literature ( Supplementary Materials, Figures S2–S17, S20–S25, S32–S35 and Tables S1–S4 ).…”

Section: Resultsmentioning

confidence: 99%

“…Chromatographic fractionation and further purification of the crude ethyl acetate extract of the cultures of A. candidus KUFA 0062, furnished two previously undescribed compounds named candidusin D ( 2e ) and preussin C ( 5b ), as well as the previously reported chrysophanic acid ( 1a ) [ 13 ], emodin ( 1b ) [ 14 ], six bis -indolyl benzenoids including asterriquinol D dimethyl ether ( 2a ) [ 15 ], petromurin C ( 2b ) [ 16 ], kumbicin B ( 2c ) [ 15 ], kumbicin A ( 2d ) [ 15 ], 2″-oxoasterriquinol D methyl ether ( 3 ) [ 17 ], kumbicin D ( 4 ) [ 15 ], the hydroxypyrrolidine alkaloid preussin ( 5a ) [ 18 , 19 , 20 ], (3 S , 6 S )-3,6-dibenzylpiperazine-2,5-dione ( 6 ) [ 21 ], and 4-(acetylamino) benzoic acid ( 7 ) [ 22 ] ( Figure 1 ). Additionally, the common fungal metabolites, i.e., palmitic acid, clionasterol [ 23 ], and ergosterol 5,8-endoperoxides [ 14 ] were also isolated ( Supplementary Material, Figure S1 ).…”

Section: Introductionmentioning

confidence: 99%

Bis-Indolyl Benzenoids, Hydroxypyrrolidine Derivatives and Other Constituents from Cultures of the Marine Sponge-Associated Fungus Aspergillus candidus KUFA0062

et al. 2018

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A previously unreported bis-indolyl benzenoid, candidusin D (2e) and a new hydroxypyrrolidine alkaloid, preussin C (5b) were isolated together with fourteen previously described compounds: palmitic acid, clionasterol, ergosterol 5,8-endoperoxides, chrysophanic acid (1a), emodin (1b), six bis-indolyl benzenoids including asterriquinol D dimethyl ether (2a), petromurin C (2b), kumbicin B (2c), kumbicin A (2d), 2″-oxoasterriquinol D methyl ether (3), kumbicin D (4), the hydroxypyrrolidine alkaloid preussin (5a), (3S, 6S)-3,6-dibenzylpiperazine-2,5-dione (6) and 4-(acetylamino) benzoic acid (7), from the cultures of the marine sponge-associated fungus Aspergillus candidus KUFA 0062. Compounds 1a, 2a–e, 3, 4, 5a–b, and 6 were tested for their antibacterial activity against Gram-positive and Gram-negative reference and multidrug-resistant strains isolated from the environment. Only 5a exhibited an inhibitory effect against S. aureus ATCC 29213 and E. faecalis ATCC29212 as well as both methicillin-resistant S. aureus (MRSA) and vancomycin-resistant enterococci (VRE) strains. Both 1a and 5a also reduced significant biofilm formation in E. coli ATCC 25922. Moreover, 2b and 5a revealed a synergistic effect with oxacillin against MRSA S. aureus 66/1 while 5a exhibited a strong synergistic effect with the antibiotic colistin against E. coli 1410/1. Compound 1a, 2a–e, 3, 4, 5a–b, and 6 were also tested, together with the crude extract, for cytotoxic effect against eight cancer cell lines: HepG2, HT29, HCT116, A549, A 375, MCF-7, U-251, and T98G. Except for 1a, 2a, 2d, 4, and 6, all the compounds showed cytotoxicity against all the cancer cell lines tested.

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“…We have also established a flexible approach to prepare trans-5-alkyl-4-benzyloxy-2-pyrrolidinones 14 and trans-6-alkyl-5-benzyloxy-2-piperidinones 15 (Scheme 2), [6] which were used as key intermediates in the stereoselective syntheses of several natural products and pharmaceuticals such as nemonapride (1), [6c] (R)-ypaoamide (2), [7] hapalosin (3), [8] morusimic acid D (8), [9] and awajanomycin (9). [10] To access cis-5-alkyl-4-benzyloxy-2-pyrrolidinones, which are useful building blocks for the syntheses of natural products and drugs such as preussin (4), [11] streptopyrrolidine (5), [12] (2S,3S)-L-733,060 (7), and b-hydroxy-g-amino acids such as 6 a-6 c, two stepwise methods have been developed. [13,14] In view of a step-economical synthesis, [3] a versatile and direct approach to cis-5-alkyl-4-hydroxy-2-pyrroli-dinones and cis-6-alkyl-5-hydroxy-2-piperidinones is highly desirable.…”

Section: Introductionmentioning

confidence: 99%

Towards Reaction Control: cis‐Diastereoselective Reductive Dehydroxylation of 5‐Alkyl‐4‐Benzyloxy‐5‐Hydroxy‐2‐Pyrrolidinones

Wang

Xie

et al. 2012

Asian J Org Chem

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A chemo-, regio-, and stereoselectively controlled reaction is highly desirable, yet challenging in organic synthesis. Diversely substituted cis and trans isomers of 2-alkyl-3-pyrrolidinols, 5-alkyl-4-hydroxy-2-pyrrolidinones, b-hydroxy-g-amino acids, and their higher homologues are key structural units found in numerous drugs, drug candidates, and bioactive natural products. Previously, we established a flexible approach to trans-5-alkyl-4-benzyloxy-2-pyrrolidinones 14 and trans-6-alkyl-5-benzyloxy-2-piperidinones 15. Herein, we report a direct, flexible, moisture insensitive, and highly diastereoselective approach to the corresponding cis diastereomers 16. This stereocontrolled method is based on the MsOH-mediated (Ms = methane sulfonyl) reductive dehydroxylation of hemiaminal 12 with NaBHA C H T U N G T R E N N U N G (OAc) 3 . cis-5-Alkyl-4benzyloxy-2-pyrrolidinones 16 are useful building blocks for the syntheses of natural products such as (+)-preussin (4) and streptopyrrolidine (5) as well as (3S,4S)-g-alkyl-bhydroxy-g-amino acids (6).

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The relative and absolute stereochemistry of the antifungal agent preussin.

Cited by 72 publications

References 2 publications

Inhibition of Cyclin-Dependent Kinase Activity and Induction of Apoptosis by Preussin in Human Tumor Cells

Inhibition of Cyclin-Dependent Kinase Activity and Induction of Apoptosis by Preussin in Human Tumor Cells

Bis-Indolyl Benzenoids, Hydroxypyrrolidine Derivatives and Other Constituents from Cultures of the Marine Sponge-Associated Fungus Aspergillus candidus KUFA0062

Towards Reaction Control: cis‐Diastereoselective Reductive Dehydroxylation of 5‐Alkyl‐4‐Benzyloxy‐5‐Hydroxy‐2‐Pyrrolidinones

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