Preclinical data on morpholine (3,5-di-tertbutyl-4-hydroxyphenyl) methanone induced anxiolysis

Cabral, Iara Barbosa; Moreira, Caroline Vitória de Lima; Rodrigues, Ana Carolina Cavalcante; Moreira, Lorrane Kelle da Silva; Pereira, Jhon Kennedy Alves; Gomides, Christian Dias; Lião, Luciano Morais; Machado, Lucas Santos; Vaz, Boniek G.; Cunha, Luíz Carlos da; Neto, Jerônimo Raimundo de Oliveira; Silva-Júnior, Edeildo Ferreira da; Aquino, Thiago Mendonça de; Santos-Júnior, Paulo Fernando da Silva; Rocha, Fábio Fagundes da; Costa, Élson Alves; Menegatti, Ricardo; Fajemiroye, James Oluwagbamigbe

doi:10.1007/s00210-023-02502-9

Cited by 1 publication

(7 citation statements)

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“…It is very well known that BHT (1) exhibits reversible electrochemical behavior at peak potentials lower than 0.4 V (neutral pH), which in fact explains its widespread use as an antioxidant [24,[27][28][29][30][31]. The reversibility of the BHT (1) moiety of LQFM 289 (3) was confirmed with SWV (Figure 2B, inset).…”

Section: Computational Data and Electrochemical Characterizationmentioning

confidence: 71%

“…In a previous work, LQFM289 (3) 10 mg/kg induced anxiolytic-like activity in mice without interfering with the animals' motor activity [27]. The anxiolytic-like effects of LQFM289 (3) (10 mg/kg) were attenuated by flumazenil pretreatment, which suggests the participation of benzodiazepine binding sites.…”

Section: Introductionmentioning

confidence: 67%

Section: Introductionmentioning

confidence: 86%

“…The docking of LQFM289 (3) showed strong interactions with benzodiazepine binding sites and matched well with receptor binding data. LQFM289 (3) also lowered corticosterone and tumor necrosis factor alpha levels in LQFM289 (3)-treated mice at a single oral dose of 10 mg/kg, which suggests that the anxiolytic-like effect observed in this compound can modulate other pathways [27]. In addition, owing to the electroactivity of BHT (1) and its derivatives, electroanalysis emerges as a promising tool to evaluate its redox properties, which may be useful in complementary chemical characterization, and also to estimate the oxidative stability and antioxidant properties of the compound, as well as offering an analytical target for further quantitative determinations [28][29][30][31].…”

Section: Introductionmentioning

confidence: 87%

“…In order to optimize the pharmacophoric groups of TMZ, a new lead compound named LQFM289 (3) can be obtained through a molecular hybridization strategy by replacing the first trimethoxybenzene with a bioactive compound possessing a stronger antioxidant profile, butylhydroxytoluene (BHT) [23] (1), as represented in Figure 1. In addition to its antioxidant properties, which make it a common ingredient in food [24] and cosmetic products [25], some studies have revealed that BHT can enhance the potential effects of antidepressant drugs as well as anxiolytics in neurodegenerative models [26][27][28].…”

Section: Introductionmentioning

confidence: 99%

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LQFM289: Electrochemical and Computational Studies of a New Trimetozine Analogue for Anxiety Treatment

Pereira,

Costa,

Rodrigues

et al. 2023

IJMS

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This study employs electrochemical and Density Functional Theory (DFT) calculation approaches to investigate the potential of a novel analogue of trimetozine (TMZ) antioxidant profile. The correlation between oxidative stress and psychological disorders indicates that antioxidants may be an effective alternative treatment option. Butylatedhydroxytoluene (BHT) is a synthetic antioxidant widely used in industry. The BHT-TMZ compound derived from molecular hybridization, known as LQFM289, has shown promising results in early trials, and this study aims to elucidate its electrochemical properties to further support its potential as a therapeutic agent. The electrochemical behavior of LQFM289 was investigated using voltammetry and a mechanism for the redox process was proposed based on the compound’s behavior. LQFM289 exhibits two distinct oxidation peaks: the first peak, Ep1a ≈ 0.49, corresponds to the oxidation of the phenolic fraction (BHT), and the second peak, Ep2a ≈ 1.2 V (vs. Ag/AgCl/KClsat), denotes the oxidation of the amino group from morpholine. Electroanalysis was used to identify the redox potentials of the compound, providing insight into its reactivity and stability in different environments. A redox mechanism was proposed based on the resulting peak potentials. The DFT calculation elucidates the electronic structure of LQFM289, resembling the precursors of molecular hybridization (BHT and TMZ), which may also dictate the pharmacophoric performance.

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