71030-11-0Relevant academic research and scientific papers
Enantioselective total synthesis of β-zearalenol from (s)-propylene oxide
Kotla, Ravindar,Murugulla, Adharvana Chari,Ruddarraju, Radhakrishnamraju,Aparna,Donthabakthuni, Shobha,Sridhar, Gattu
, p. 747 - 752 (2018/03/29)
The total synthesis of 14-membered resorcylic acid macrolide, β-zearalenol, was accomplished starting from commercially available enantiomerically pure propylene oxide and methyl 2,4-dihydroxy-6-methylbenzoate using Grignard reaction, asymmetric dihydroxy
Synthesis and cytotoxic activities of semisynthetic zearalenone analogues
Tadpetch, Kwanruthai,Kaewmee, Benyapa,Chantakaew, Kittisak,Kantee, Kawalee,Rukachaisirikul, Vatcharin,Phongpaichit, Souwalak
supporting information, p. 3612 - 3616 (2016/07/21)
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.
In vitro phase i metabolism of cis -zearalenone
Drzymala, Sarah S.,Herrmann, Antje J.,Maul, Ronald,Pfeifer, Dietmar,Garbe, Leif-Alexander,Koch, Matthias
, p. 1972 - 1978 (2015/02/19)
The present study investigates the in vitro phase I metabolism of cis-zearalenone (cis-ZEN) in rat liver microsomes and human liver microsomes. cis-ZEN is an often ignored isomer of the trans-configured Fusarium mycotoxin zearalenone (trans-ZEN). Upon the influence of (UV-) light, trans-ZEN isomerizes to cis-ZEN. Therefore, cis-ZEN is also present in food and feed. The aim of our study was to evaluate the in vitro phase I metabolism of cis-ZEN in comparison to that of trans-ZEN. As a result, an extensive metabolization of cis-ZEN is observed for rat and human liver microsomes as analyzed by HPLC-MS/MS and high-resolution MS. Kinetic investigations based on the substrate depletion approach showed no significant difference in rate constants and half-lives for cis- and trans-ZEN in rat microsomes. In contrast, cis-ZEN was depleted about 1.4-fold faster than trans-ZEN in human microsomes. The metabolite pattern of cis-ZEN revealed a total of 10 phase I metabolites. Its reduction products, α- and β-cis-zearalenol (α- and β-cis-ZEL), were found as metabolites in both species, with α-cis-ZEL being a major metabolite in rat liver microsomes. Both compounds were identified by co-chromatography with synthesized authentic standards. A further major metabolite in rat microsomes was monohydroxylated cis-ZEN. In human microsomes, monohydroxylated cis-ZEN is the single dominant peak of the metabolite profile. Our study discloses three metabolic pathways for cis-ZEN: reduction of the keto-group, monohydroxylation, and a combination of both. Because these routes have been reported for trans-ZEN, we conclude that the phase I metabolism of cis-ZEN is essentially similar to that of its trans isomer. As trans-ZEN is prone to metabolic activation, leading to the formation of more estrogenic metabolites, the novel metabolites of cis-ZEN reported in this study, in particular α-cis-ZEL, might also show higher estrogenicity.
Preparative enzymatic synthesis of glucuronides of zearalenone and five of its metabolites
Stevenson, David E.,Hansen, Richard P.,Loader, Jared I.,Jensen, Dwayne J.,Cooney, Janine M.,Wilkins, Alistair L.,Miles, Christopher O.
experimental part, p. 4032 - 4038 (2010/03/31)
The resorcylic acid lactones zearalenone (1), α-zearalenol (2), β-zearalenol (3), α-zearalanol (zeranol) (4), β-zearalanol (taleranol) (5), and zearalanone (6) were converted to their glucuronides on a preparative scale in good yields. Reactions were conducted with bovine uridine 5′-diphosphoglucuronyl transferase (UDPGT) as catalyst and uridine 5′-diphosphoglucuronic acid (UDPGA) as cofactor. The glucuronides were isolated by column chromatography and characterized by NMR spectroscopy and mass spectrometry. Although the principal products were 4-O-glucuronides (i.e., linkage through a phenolic hydroxyl), significant quantities of the 6′-O-glucuronides (i.e., linkage through the aliphatic hydroxyl) of alcohols 2, 4, and 5 were also isolated. In the case of 3, the 2-O-glucuronide was isolated as the minor product. Overall isolated yields of glucuronides, performed on a 20-50 mg scale, were typically ca. 80% based on the resorcylic acid lactone starting material. LC-UV-MS2 analysis of purified specimens revealed MS2 fragmentations useful for defining the point of attachment of the glucuronide moiety to the zearalenone nucleus.
The use of π-allyltricarbonyliron lactone complexes in the synthesis of the resorcylic macrolides α- and β-zearalenol
Burckhardt, Svenja,Ley, Steven V.
, p. 874 - 882 (2007/10/03)
A highly stereoselective synthesis of the natural products α- and β-zearalenol 1 and 2 has been achieved using π-allyltricarbonyliron lactone complexes to control the 1,5-stereochemical relationship of the oxygen functionalities found in these resorcylic macrolides.
The use of π-allyltricarbonyliron lactone complexes in the synthesis of the resorcylic macrolides α- and β-zearalenol
Ley, Steven V.,Burckhardt, Svenja
, p. 3028 - 3030 (2007/10/03)
A highly stereoselective synthesis of α- and β-zearalenol 1 and 2 is accomplished utilising π-allyltricarbonyliron lactone complexes 5 and 6 to establish the 1,5-stereochemical relationship of oxygen functionalities present in the natural products. The Royal Society of Chemistry 2000.
Enzymatic kinetic separation of stereoisomeric macrocyclic lactone derivatives, 7α,β-O-acyl trans-zearalenols and 7α,β-O-acyl zearanols
Gelo, Mirjana,Sunjic, Vitomir
, p. 6511 - 6520 (2007/10/02)
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
Microbial Transformation of Zearalenone. 2. Reduction, Hydroxylation, and Methylation Products
El-Sharkawy, Saleh H.,Abul-Hajj, Yusuf J.
, p. 515 - 519 (2007/10/02)
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.
