Molecular Docking of Cryptoconcatones to α-Tubulin and Related Pironetin Analogues
Cryptoconcatones A-L represent a series of 12 dihydropyrone derivatives isolated from the evergreen tree <i>Cryptocarya concinna</i> Hance, which is well distributed in southeast Asia. The lead compound in the series, cryptoconcatone L, has revealed antiproliferative activity against cul...
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MDPI AG
2023-01-01
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| Series: | Plants |
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| Online Access: | https://www.mdpi.com/2223-7747/12/2/296 |
| _version_ | 1797437672003731456 |
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| author | Gérard Vergoten Christian Bailly |
| author_facet | Gérard Vergoten Christian Bailly |
| author_sort | Gérard Vergoten |
| collection | DOAJ |
| description | Cryptoconcatones A-L represent a series of 12 dihydropyrone derivatives isolated from the evergreen tree <i>Cryptocarya concinna</i> Hance, which is well distributed in southeast Asia. The lead compound in the series, cryptoconcatone L, has revealed antiproliferative activity against cultured cancer cells but its mechanism of action remains unknown. Based on a structural analogy with the anticancer natural product pironetin, which is well known for binding covalently to α-tubulin and for functioning as a microtubule polymerization inhibitor, we investigated the interaction of cryptoconcatones with tubulin dimers using molecular docking. The α-tubulin binding capacity of each compound was quantified (through calculation of the empirical energy of interaction Δ<i>E</i>) and structure–binding relationships were delineated. Two compounds were found to interact with α-tubulin much more potently than pironetin: cryptoconcatones F and L. In both cases, the facile formation of a covalent bond with Cys316 was evidenced, as observed with the parent compound pironetin. A few other pironetin analogues were investigated, including spicigerolide, which is an analogue of another known α-tubulin binder. Altogether, this study points to the identification of a series of 5,6-dihydro-α-pyrones as α-tubulin-binding agents. The study contributes to a better understanding of the mechanism of action of cryptoconcatones and should help the design of analogues targeting the pironetin site of α-tubulin. |
| first_indexed | 2024-03-09T11:25:58Z |
| format | Article |
| id | doaj.art-d81928f072054912b25d0ad97e0a7dcb |
| institution | Directory Open Access Journal |
| issn | 2223-7747 |
| language | English |
| last_indexed | 2024-03-09T11:25:58Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Plants |
| spelling | doaj.art-d81928f072054912b25d0ad97e0a7dcb2023-12-01T00:04:19ZengMDPI AGPlants2223-77472023-01-0112229610.3390/plants12020296Molecular Docking of Cryptoconcatones to α-Tubulin and Related Pironetin AnaloguesGérard Vergoten0Christian Bailly1Institut de Chimie Pharmaceutique Albert Lespagnol (ICPAL), Faculté de Pharmacie, University of Lille, 3 rue du Professeur Laguesse, BP-83, F-59006 Lille, FranceInstitut de Chimie Pharmaceutique Albert Lespagnol (ICPAL), Faculté de Pharmacie, University of Lille, 3 rue du Professeur Laguesse, BP-83, F-59006 Lille, FranceCryptoconcatones A-L represent a series of 12 dihydropyrone derivatives isolated from the evergreen tree <i>Cryptocarya concinna</i> Hance, which is well distributed in southeast Asia. The lead compound in the series, cryptoconcatone L, has revealed antiproliferative activity against cultured cancer cells but its mechanism of action remains unknown. Based on a structural analogy with the anticancer natural product pironetin, which is well known for binding covalently to α-tubulin and for functioning as a microtubule polymerization inhibitor, we investigated the interaction of cryptoconcatones with tubulin dimers using molecular docking. The α-tubulin binding capacity of each compound was quantified (through calculation of the empirical energy of interaction Δ<i>E</i>) and structure–binding relationships were delineated. Two compounds were found to interact with α-tubulin much more potently than pironetin: cryptoconcatones F and L. In both cases, the facile formation of a covalent bond with Cys316 was evidenced, as observed with the parent compound pironetin. A few other pironetin analogues were investigated, including spicigerolide, which is an analogue of another known α-tubulin binder. Altogether, this study points to the identification of a series of 5,6-dihydro-α-pyrones as α-tubulin-binding agents. The study contributes to a better understanding of the mechanism of action of cryptoconcatones and should help the design of analogues targeting the pironetin site of α-tubulin.https://www.mdpi.com/2223-7747/12/2/296anticancer agents<i>Cryptocarya</i> speciescryptoconcatonespironetintubulin binding |
| spellingShingle | Gérard Vergoten Christian Bailly Molecular Docking of Cryptoconcatones to α-Tubulin and Related Pironetin Analogues Plants anticancer agents <i>Cryptocarya</i> species cryptoconcatones pironetin tubulin binding |
| title | Molecular Docking of Cryptoconcatones to α-Tubulin and Related Pironetin Analogues |
| title_full | Molecular Docking of Cryptoconcatones to α-Tubulin and Related Pironetin Analogues |
| title_fullStr | Molecular Docking of Cryptoconcatones to α-Tubulin and Related Pironetin Analogues |
| title_full_unstemmed | Molecular Docking of Cryptoconcatones to α-Tubulin and Related Pironetin Analogues |
| title_short | Molecular Docking of Cryptoconcatones to α-Tubulin and Related Pironetin Analogues |
| title_sort | molecular docking of cryptoconcatones to α tubulin and related pironetin analogues |
| topic | anticancer agents <i>Cryptocarya</i> species cryptoconcatones pironetin tubulin binding |
| url | https://www.mdpi.com/2223-7747/12/2/296 |
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