- Synthesis and cytotoxic activities of semisynthetic zearalenone analogues
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Zearalenone is a β-resorcylic acid macrolide with various biological activities. Herein we report the synthesis and cytotoxic activities of 34 zearalenone analogues against human oral epidermoid carcinoma (KB) and human breast adenocarcinoma (MCF-7) cells as well as noncancerous Vero cells. Some zearalenone analogues showed moderately enhanced cytotoxic activities against the two cancer cell lines. We have discovered the potential lead compounds with diminished or no cytotoxicity to Vero cells. Preliminary structure–activity relationship studies revealed that the double bond at the 1′ and 2′ positions of zearalenone core was crucial for cytotoxic activities on both cell lines. In addition, for zearalenol analogues, the unprotected hydroxyl group at C-2 and an alkoxy substituent at C-4 played key roles on cytotoxic effects of both cell lines.
- Tadpetch, Kwanruthai,Kaewmee, Benyapa,Chantakaew, Kittisak,Kantee, Kawalee,Rukachaisirikul, Vatcharin,Phongpaichit, Souwalak
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p. 3612 - 3616
(2016/07/21)
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- Pochonins A-F, new antiviral and antiparasitic resorcylic acid lactones from Pochonia chlamydosporia var. catenulata
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Monorden (1) and the novel resorcylic acid lactones pochonins A (2), B (4), C (6), D (7), and E (8) as well as tetrahydromonorden (5) and pseurotin A (22) were isolated from cultures of the clavicipitaceous hyphomycete Pochonia chlamydosporia var. catenulata strain P 0297. Fermentation of P 0297 in bromide-containing culture media led to a shift in secondary metabolite production and yielded monocillins III (3) and II (9) as major metabolites besides monorden (1) as well as the novel compounds pochonin F (10) and a monocillin II glycoside (11) as minor metabolites. Most of these compounds showed moderate activities in a cellular replication assay against Herpes Simplex Virus 1 (HSV1) and against the parasitic protozoan Eimeria tenella. In contrast to the structurally related zearalenone derivatives none of the metabolites of strain P 0297 were found to be active in a fluorescence polarization assay for determination of modulatory activities on the human estrogenic receptor ERβ. β-Zearalenol (17), but not zearalenone (15) and α-zearalenol (16), showed antiherpetic effects. We report the production, isolation, and structure elucidation of compounds 1-11 and their biological characterization.
- Hellwig, Veronika,Mayer-Bartschmid, Anke,Müller, Hartwig,Greif, Gisela,Kleymann, Gerald,Zitzmann, Werner,Tichy, Hans-Volker,Stadler, Marc
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p. 829 - 837
(2007/10/03)
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- Comparative study of conformational effects on stereoselective lipase catalysed acetylation of sec hydroxy groups in diastereomeric 14-membered lactones and their acyclic analogs
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Stereoselective acetylation of sec hydroxy groups in a diastereomeric (1:1) mixture of macrocyclic lactones 14, 15, catalysed by seven microbial lipases in n-heptane afforded the C(7)-O-acetyl derivative 17 with up to 99% diastereomeric excess (d.e.), whereas acetylation of their acyclic analogs 10, 11 afforded C(5)-O-acetyl derivative 13 with up to 93% d.e. Six lipases, from Pseudomonas cepacia (PCL), Pseudomonas fluorescens (PFL), Geotrichum candidum (GCL), Candida cylindracea (CCL) and Pseudomonas cepacia immobilised on ceramics (PS-C) predominantly acetylate cyclic diastereomer (3S,7S)-15 to (3S,7S)-17; only Candida antarctica-B (CAL-B) lipase predominantly acetylates (3S,7R)-14 to (3S,7R)-16. With acyclic analogs 10, 11 the same set of lipases exhibited different diastereoselective bias; CAL-B, GCL and CCL predominantly acylate (1S,5S)-11 to (1S,5S)-13, whereas PCL, PS-C, PFL and PSL acylate predominantly (1S,5R)-10 to (1S,5R)-12. Only GCL exhibited higher stereoselectivity for an acyclic pair of stereoisomers with higher conformational flexibility, over cyclic diastereomeric substrates with a conformationally restricted macrocyclic ring. The preference of PCL for macrocyclic substrates is particularly interesting, in view of the recently suggested binding mode of a series of acyclic sec alcohols in the extended conformation. (C) 2000 Elsevier Science Ltd.
- Ljubovic,Sunjic
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p. 9135 - 9138
(2007/10/03)
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- Enzymatic kinetic separation of stereoisomeric macrocyclic lactone derivatives, 7α,β-O-acyl trans-zearalenols and 7α,β-O-acyl zearanols
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Diastereomeric mixtures of resorcyclic acid macrocyclic lactones, 7α,β-O-acyl zearalenols (1,2 and 3,4 full name: trans-3,4,5,6,9,10-octahydro-14,16-dihydroxy-7-acyloxy-3-methyl 1H-2-benzoxacyclotetradecin-1-ones (3S,7S or 3S,7R)), and 7α,β-acyl zearanols
- Gelo, Mirjana,Sunjic, Vitomir
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p. 6511 - 6520
(2007/10/02)
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- Microbial Transformation of Zearalenone. 2. Reduction, Hydroxylation, and Methylation Products
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Microbial transformations have been employed as a means of preparing analogues of the resorcylic acid lactone zearalenone.Microbial transformation products were initially identified by thin-layer chromatography of fermentation extracts and then prepared by large-scale incubations.Each metabolite was subjected to structural elucidation employing carbon-13 and proton NMR, mass spectrometry, and infrared analysis.Metabolites were identified as α- and β-zearalenol, α- and β-zearalanol, zearalanone, 8'(S)-hydroxyzearalenone, 2,4-dimethoxyzearalenone, and 2-methoxyzearalenone.Binding affinities to rat uterine estrogen receptors were carried out.Only those metabolites having a free 4-phenolic group were capable of binding to the estrogen receptor.However, 8'-hydroxyzearalenone, even with a 4-phenolic hydroxyl, did not bind to the receptor.It is possible that hydrogen bonding of the aliphatic hydroxyl groups to the C-6' carbonyl of zearalenone or equilibrium between the hydroxy ketone and its tautomeric hemiketal may lead to distortion of the conformation of the molecule resulting in loss of binding to the receptor.
- El-Sharkawy, Saleh H.,Abul-Hajj, Yusuf J.
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p. 515 - 519
(2007/10/02)
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