Distribution of 5,6-dihydro-α-pyrones by electrospray ionization ion trap mass spectrometry in different aerial parts of Hyptis monticola

Silva, Aline Soares da; Martínez-Fructuoso, Lucero; Simas, Rosineide C.; Leitão, Gilda Guimarães; Fragoso‐Serrano, Mabel; Barros, Yasmim Santana; Souza, Diego Ramalho de; Pereda‐Miranda, Rogelio; Leitão, Suzana Guimarães

doi:10.1016/j.phytochem.2021.112706

Cited by 2 publications

(1 citation statement)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In conclusion, our work, entirely consistent with other observations, attests that the cryptoconcatone and pironetin scaffolds can be further exploited to design anticancer agents. There exists a variety of 5,6-dihydro-α-pyrones in plants, such as monticolides [ 49 ], pulchrinervialactone [ 50 ], cryptorigidifoliols [ 51 ], cryptomoscatones [ 36 ] and others. All these compounds should be tested as modulators of microtubule dynamics.…”

Section: Discussionmentioning

confidence: 99%

Molecular Docking of Cryptoconcatones to α-Tubulin and Related Pironetin Analogues

Vergoten

Bailly

2023

Plants

View full text Add to dashboard Cite

Cryptoconcatones A-L represent a series of 12 dihydropyrone derivatives isolated from the evergreen tree Cryptocarya concinna 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 ΔE) 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.

show abstract