A phenolic ether 2-methoxy-carvacrol isolated from Rhabdocaulon lavanduloides (Benth) Epling. (Lamiaceae): New crystal structure, Hirshfeld surface, quantum chemical calculation, anxiolytic and anticonvulsant potential in zebrafish, and molecular docking of GABAA receptor

IF 4 2区化学 Q2 CHEMISTRY, PHYSICAL

Journal of Molecular Structure Pub Date : 2025-03-02 DOI:10.1016/j.molstruc.2025.141927

Moises Bruno Marinho Rocha , Luiz Everson da Silva , Wanderlei do Amaral , Cícero Deschamps , Ricardo Andrade Rebelo , Iêda Maria Begnini , Adriana Daniel Boyen , Maria Kueirislene Amâncio Ferreira , Francisco Rogenio da Silva Mendes , Emmanuel Silva Marinho , Marcia Machado Marinho , Emanuel Paula Magalhães , Ramon Róseo Paula Pessoa Bezerra de Menezes , Antônio César Honorato Barreto , Alejandro Pedro Ayala , Alexandre Magno Rodrigues Teixeira , Jane Eire Silva Alencar de Menezes , Hélcio Silva dos Santos

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Abstract

The drugs that treat anxiety disorder have variable efficacy and associated side effects. This study evaluated the anxiolytic and anticonvulsant potential of natural product 2-methoxy-carvacrol isolated from Rhabdocaulon lavanduloides, its respective mechanism of action in adult zebrafish (ZFa), in addition to an in silico. Each animal (n=6/group) was treated intraperitoneally (i.p.; 20 µL) with the natural product (4, 20 and 40 mg/Kg) and with the vehicle (DMSO 3 %; 20 µL), being submitted to the tests of locomotor activity and 96 h acute toxicity. The study showed that 2-methoxy-carvacrol was not toxic in the assessment of locomotion behavior of adult zebrafish at all doses evaluated. The two highest doses displayed anxiolytic effect, and when examining the mechanism of action, it was found that this effect is neuromodulated by the GABAergic pathway. Furthermore, the sample was able to reverse the convulsive behavior of the animals in the early stage of analysis (Stage I). Molecular docking simulations indicate that 2-methoxy-carvacrol has a distinct affinity from that of the co-crystallized inhibitor, suggesting allosteric activity. Furthermore, its interactions with the GABAAR receptor are like those of DZP, highlighting potential anxiolytic effects. The pharmacokinetic test showed that PAMPA suggests high cellular permeability for potential intestinal absorption.

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来源期刊

Journal of Molecular Structure 化学-物理化学

CiteScore

7.10

自引率

15.80%

发文量

2384

审稿时长

45 days

期刊介绍： The Journal of Molecular Structure is dedicated to the publication of full-length articles and review papers, providing important new structural information on all types of chemical species including: • Stable and unstable molecules in all types of environments (vapour, molecular beam, liquid, solution, liquid crystal, solid state, matrix-isolated, surface-absorbed etc.) • Chemical intermediates • Molecules in excited states • Biological molecules • Polymers. The methods used may include any combination of spectroscopic and non-spectroscopic techniques, for example: • Infrared spectroscopy (mid, far, near) • Raman spectroscopy and non-linear Raman methods (CARS, etc.) • Electronic absorption spectroscopy • Optical rotatory dispersion and circular dichroism • Fluorescence and phosphorescence techniques • Electron spectroscopies (PES, XPS), EXAFS, etc. • Microwave spectroscopy • Electron diffraction • NMR and ESR spectroscopies • Mössbauer spectroscopy • X-ray crystallography • Charge Density Analyses • Computational Studies (supplementing experimental methods) We encourage publications combining theoretical and experimental approaches. The structural insights gained by the studies should be correlated with the properties, activity and/ or reactivity of the molecule under investigation and the relevance of this molecule and its implications should be discussed.