Naslov
In silico ADMET Properties of Methoxy-propenyl-1,3-benzodioxoles and Methoxy-propenyl-benzenes – QSAR Study

Autori
Jadrijević-Mladar Takač, Milena ; Takač, Tin

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Workshop Program - QSAR 2021 – From QSAR to New Approach Methodologies, 19th International Workshop on (Quantitative) Structure-Activity in Environmental and Health Sciences / - Gaithersburg (MD) : The International Council of Chemical Associations Long-Range Research Initiative (ICCA-LRI), 2021, 18-18

Skup
19th International Workshop on (Quantitative) Structure-Activity Relationships in Environmental and Health Sciences (QSAR 2021)

Mjesto i datum
Gaithersburg (MD), Sjedinjene Američke Države, 07.06.2021. - 09.06.2021

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Methoxy-propenyl-1, 3-benzodioxoles ; Methoxy-propenyl-benzenes ; Naturally occuring bioactive ethers ; Myristicin ; Elemicin ; ADMET, Ecotoxicity
(Methoxy-propenyl-1, 3-benzodioxoles ; Methoxy-propenyl-benzenes ; Naturally bioactive ethers ; Myristicin ; Elemicin ; ADMET, Ecotoxicity)

Sažetak
Naturally occurring ethers from the group of methoxy-propenyl-1, 3-benzodioxoles and methoxy-propenyl-benzenes are biologically active compounds, and those like myristicin and elemicin, the two main constituents of the nutmeg essential oil, are assumed to be responsible for the experienced psychoactivity as a result of nutmeg consumption. The metabolic conversion of these compounds into amphetamine similar to 3-methoxy-4, 5-methylenedioxy-amphetamine (MMDA), a precursor of ecstasy (MDMA), and 3, 4, 5- trimethoxyamphetamine (TMA), respectively, have been proposed as the mechanism for the psychoactivity of these compounds. In this QSAR study, the relationship between ADMET properties of methoxy-propenyl-1, 3-benzodioxolones and methoxy-propenyl-benzenes (n =29) predicted by ADMET PredictorTM was evaluated. The MDMA was also included in this study. The majority of the investigated compounds were revealed as nonbiodegradable, except for several mono-methoxy-propenyl-benzenes. The bioconcentration factor of these molecules was predicted in a wide range, from 6.228 to 965.605. According to ECCS, all compounds belong to Class 2 (neutral or basic compounds with high permeability, predominantly cleared by metabolism). The main ADMET risk connected with CYP1A2 oxidation was revealed for all investigated compounds. However, the risk of mutagenicity was predicted for isomyristicin, croweacin, asaricin, apiol, isoapiol, and nothoapiol, and the risk of hepatotoxicity for piperonal, chavicol, eugenol, and isoeugenol. All molecules were predicted to be skin sensitizers. QSAR study revealed the best correlations between lipophilicity (MlogP) vs. CYP2C19_Km (R2=0.869), and vs. Andro_RBA (R2=0.735), as well as between permeability, S+Peff, vs. CYP2C19_Km (R2=0.717), vs. CYP3A4_Ki_testo (R2=0.720), and vs. Rat_Acute (R2=0.703).

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Farmacija

Napomena
Skup je održan virtualno.

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