Combining DFT and QSAR studies for predicting psychotomimetic activity of substituted phenethylamines using statistical methods

Aouidate, Adnane; Ghaleb, Adib; Ghamali, Mounir; Chtita, Samir; Choukrad, M’barek; Sbai, Abdelouahid; Bouachrine, Mohammed; Lakhlifi, Tahar

doi:10.1016/j.jtusci.2016.07.001

Cited by 9 publications

(15 citation statements)

References 19 publications

(24 reference statements)

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“…Among the introduced previous QSAR models, only Aouidate et al [8a] . used external validation for the assessment of their models.…”

Section: Methodsmentioning

confidence: 99%

“…Available QSAR models for the prediction of the psychotomimetic activity of the substituted require physico‐chemical as well as electronic and charge descriptors [8] . For example, Aouidate et al [8a] . used a quantum mechanical DFT‐B3LYP method with the base set 6–31G (d) to calculate electronic and charge descriptors.…”

Section: Introductionmentioning

confidence: 99%

“…The largest experimental data of the psychotomimetic activity of 116 of the substituted phenethylamines are used to derive and test the new model. The reliability of this approach is compared with the outputs of the external validation test of two MLR and MNLR models of Aouidate et al [8a] . as well as some compounds of different classes of the substituted phenethylamines.…”

Section: Introductionmentioning

confidence: 99%

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A simple method for assessing the psychotomimetic activity of the substituted phenethylamines

Keshavarz

Shirazi

Rezayat

2021

Zeitschrift anorg allge chemie

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A novel approach is introduced for the prediction of the psychotomimetic activity of the substituted phenethylamines as psychedelic drugs. In contrast to the available quantitative structure-activity relationship (QSAR) methods where they need complex computer codes, unusual descriptors, and expert users, it requires the molecular structure of the desired phenethylamine derivative. The largest reported values for 116 different substituted phenethylamines are used to derive and test the new correlation by 93 and 23 experimental data, respectively. The new correlation is based on the contributions of specific isomers under certain conditions and halogen atoms. Cross validations of the new correlation corresponding to the coefficients of determination for leave-one-out (Q 2 LOO) and the leave-many-out (Q 2 LMO) are the same and equal to 0.895, which is close to the coefficient of determination (R 2 = 0.900) of the training set. Further statistical parameters also confirm the goodness-of-fit, goodness-of-prediction, accuracy, and precision of the novel model. For eleven compounds where their outputs of external validation data set of psychotomimetic activity from multiple linear regression analysis (MLR) and non-linear multiple regression analysis (MNLR) QSAR models were available, the values of root mean squared error (RMSE) of the new model, MLR and MNLR are 0.172, 0.624 and 0.539, respectively.

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“…Among the introduced previous QSAR models, only Aouidate et al [8a] . used external validation for the assessment of their models.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A simple method for assessing the psychotomimetic activity of the substituted phenethylamines

Keshavarz

Shirazi

Rezayat

2021

Zeitschrift anorg allge chemie

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“…[45][46][47][48][49][50][51][52][53] There are also few QSAR studies involving these molecules. 28,[54][55][56][57][58][59][60][61][62][63][64][65] In view of this scenario, the present study has sought to obtain a QSAR model that can assess the potential risk of amphetamine-type substances on the basis of the common structure of amphetamines and cathinones. To evaluate this possibility, we have studied a set of 26 derivatives with in vitro measured activity against NET.…”

Section: Introductionmentioning

confidence: 99%

In silico Risk Assessment Studies of New Psychoactive Substances Derived from Amphetamines and Cathinones

Melo¹,

Martins²,

Rodrigues³

et al. 2020

J. Braz. Chem. Soc.

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The amount and variety of new psychoactive substances (NPS) are expanding, and there are difficulties in assessing their risks. In this regard, in silico methods are potentially useful to predict NPS properties faster and at a lower cost. In this work a quantitative structure-activity relationship (QSAR) model was used to verify the risk of drugs derived from amphetamines and cathinones. A dataset of 26 derivatives with in vitro affinity for norepinephrine transporter (NET) was selected. To ensure reproducibility of the results, only geometric molecular descriptors (AM1 (Austin model 1) level) obtained from the platform ChemDes and ordered predictors selection (OPS) were used. The model presents good internal statistics (n = 23; coefficient of determination (R 2) = 0.914). The small number of samples was divided into seven training sets (n = 17) and seven test sets (n = 6). The average R 2 pred = 0.754 showed that the model has good predictive capacity. Based on the tests, this model can accurately predict the risk range of three previously selected derivatives: methedrone (low), ethcathinone (medium), and methamphetamine (high), even when only data referring to NET are employed. We used these data to create a simple free program in Java that focuses on the risk assessment of recreational drugs belonging to this class of compounds.

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“…Evidence for the distinction of entactogens from both methamphetamine and psychedelics ( Fig. 1) comes from structure-activity relationship (SAR) studies and animal models (6,7).…”

mentioning

confidence: 99%

Evaluation of phenylethylamine type entactogens and their metabolites relevant to ecotoxicology – a QSAR study

Takač

Magina

Takać³

2019

Acta Pharmaceutica

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The impact of the selected entactogens and their o-quinone metabolites on the environment was explored in QSAR studies by the use of predicted molecular descriptors, ADMET properties and environmental toxicity parameters, i.e., acute toxicity in Tetrahymena pyriformis (TOX_ATTP) expressed as Th_pyr_pIGC50/mmol L−1, acute toxicity in Pimephales promelas, the fathead minnow (TOX_FHM) expressed as Minnow LC50/mg L−1, the acute toxicity in Daphnia magna (TOX_DM) expressed as Daphnia LC50/mg L−1 and bioconcentration factor (BCF). The formation of corresponding o-quinones via benzo-dioxo-lone ring, O-demethylenation was predicted as the main metabolic pathway for all entactogens except for 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)propan-2-amine (DiFMDA). The least favourable ADMET profile was revealed for N-(1-(benzo[d][1,3]dioxol-5-yl)propan-2-yl)-O-methylhydroxylamine (MDMEO). QSAR studies revealed significant linear correlations between MlogP of entactogens and MlogP of o-quinone metabolites (R = 0.99), and Th_pyr_pIGC50/mmol L−1 (R = 0.94), also their MlogPs with Minnow_LC50/mg L−1 (R = 0.80 and R = 0.78), BCF (R = 0.86 and R = 0.82) and percentage of o-quinones’ yields (R = 0.73 and R = 0.80). Entactogens were predicted as non-biodegradable molecules, whereas the majority of their o-quinones were biodegradable.

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Combining DFT and QSAR studies for predicting psychotomimetic activity of substituted phenethylamines using statistical methods

Cited by 9 publications

References 19 publications

A simple method for assessing the psychotomimetic activity of the substituted phenethylamines

A simple method for assessing the psychotomimetic activity of the substituted phenethylamines

In silico Risk Assessment Studies of New Psychoactive Substances Derived from Amphetamines and Cathinones

Evaluation of phenylethylamine type entactogens and their metabolites relevant to ecotoxicology – a QSAR study

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