Higginsianins A and B, Two Diterpenoid α-Pyrones Produced by Colletotrichum higginsianum, with in Vitro Cytostatic Activity
| Autor: | Maria Chiara Zonno, Marlène Ferderin, Véronique Mathieu, Romana Lisy, Angela Boari, Angela Tuzi, Marco Evidente, Antonio Evidente, Riccardo Baroncelli, Alessio Cimmino, Marco Masi, Alexander Kornienko, Robert Kiss, Gennaro Pescitelli |
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| Přispěvatelé: | Cimmino A., Mathieu V., Masi M., Baroncelli R., Boari A., Pescitelli G., Ferderin M., Lisy R., Evidente M., Tuzi A., Zonno M.C., Kornienko A., Kiss R., Evidente A., Cimmino, Alessio, Mathieu, Veronique, Masi, Marco, Baroncelli, Riccardo, Boari, Angela, Pescitelli, Gennaro, Ferderin, Marlène, Lisy, Romana, Evidente, Marco, Tuzi, Angela, Zonno, Maria Chiara, Kornienko, Alexander, Kiss, Robert, Evidente, Antonio |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
higginsianins Circular dichroism Pharmaceutical Science Drug Screening Assays 01 natural sciences Analytical Chemistry Mice Drug Discovery Animals Circular Dichroism Colletotrichum Cytostatic Agents Diterpenes Drug Screening Assays Antitumor Humans Molecular Structure Nuclear Magnetic Resonance Biomolecular Pyrones Stereoisomerism Structure-Activity Relationship Trinidad and Tobago Drug Discovery3003 Pharmaceutical Science Pharmacology 3003 Organic Chemistry Molecular Medicine Complementary and Alternative Medicine2708 Dermatology Medicine (all) biology Chemistry Absolute configuration Colletotrichum higginsianum Epimer Stereochemistry Nuclear Magnetic Resonance biological activity Article 03 medical and health sciences Structure–activity relationship fungal metabolites biocontrol 010405 organic chemistry Antitumor biology.organism_classification Terpenoid 0104 chemical sciences 030104 developmental biology Complementary and alternative medicine diterpenoid chemical structure bioactive molecules antiproliferative activity fungal metabolites Biomolecular |
| Zdroj: | Europe PubMed Central Journal of natural products 79 (2015): 116–125. doi:10.1021/acs.jnatprod.5b00779 info:cnr-pdr/source/autori:Cimmino, Alessio; Mathieu, Veronique; Masi, Marco; Baroncelli, Riccardo; Boari, Angela; Pescitelli, Gennaro; Ferderin, Marlene; Lisy, Romana; Evidente, Marco; Tuzi, Angela; Zonno, Maria Chiara; Kornienko, Alexander; Kiss, Robert; Evidente, Antonio/titolo:Higginsianins A and B, Two Diterpenoid alpha-Pyrones Produced by Colletotrichum higginsianum, with in Vitro Cytostatic Activity/doi:10.1021%2Facs.jnatprod.5b00779/rivista:Journal of natural products (Print)/anno:2015/pagina_da:116/pagina_a:125/intervallo_pagine:116–125/volume:79 |
| DOI: | 10.1021/acs.jnatprod.5b00779 |
| Popis: | Two new diterpenoid alpha-pyrones, named higginsianins A (1) and B (2), were isolated from the mycelium of the fungus Colletotrichum higginsianum grown in liquid culture. They were characterized as 3-[5a,9b-dimethyl-7-methylene-2-(2-methylpropenyl)dodecahydronaphtho[2,1-b]furan-6-ylmethyl]-4-hydroxy-5,6-dimethylpyran-2-one and 4-hydroxy-3-[6-hydroxy-5,8a-dimethyl-2-methylene-5-(4-methylpent-3-enyl)decahydronaphthalen-1-ylmethyl]-5,6-dimethylpyran-2-one, respectively, by using NMR, HRESIMS, and chemical methods. The structure and relative configuration of higginsianin A (1) were confirmed by X-ray diffractometric analysis, while its absolute configuration was assigned by electronic circular dichroism (ECD) experiments and calculations using a solid-state ECD/TDDFT method. The relative and absolute configuration of higginsianin B (2), which did not afford crystals suitable for X-ray analysis, were determined by NMR analysis and by ECD in comparison with higginsianin A. 1 and 2 were the C-8 epimers of subglutinol A and diterpenoid BR-050, respectively. The evaluation of 1 and 2 for antiproliferative activity against a panel of six cancer cell lines revealed that the IC50 values, obtained with cells reported to be sensitive to pro-apoptotic stimuli, are by more than 1 order of magnitude lower than their apoptosis-resistant counterparts (1 vs >80 mu M). Finally, three hemisynthetic derivatives of 1 were prepared and evaluated for antiproliferative activity. Two of these possessed IC50 values and differential sensitivity profiles similar to those of 1. |
| Databáze: | OpenAIRE |
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