Assessment of the Xenobiotics Toxicity Taking into Account Their Metabolism

Filimonov, Dmitry; Дмитриев, А. В.; Rudik, Anastasia V.; Poroikov, Vladimir

doi:10.1007/978-3-031-20730-3_2

Cited by 1 publication

(1 citation statement)

References 131 publications

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“…After examining the docking studies of the two selected compounds of the previous stage and the approved drugs utilizing Moe 2019 48,49 , a proper conformer of the standard drug and compounds 306, and 580 was entered into a molecular simulation study via GROMACS 2018 50,51 . Then, the prediction of cytochrome P450 mediated metabolism for the three said compounds with the use of the SMARTCyp online server 52,53 was investigated. Finally, to maintain a reasonable level of safety prior to administration into the body, cardiotoxicity prediction was done by Pred-hERG tool 54,55 .…”

Section: Methodsmentioning

confidence: 99%

In silico discovery of potential sodium–glucose cotransporter-2 inhibitors from natural products for Prevent Kidney Failure in Patients with Type 2 Diabetes

Shakour

Hoseinpoor

Iranshahi

et al. 2023

Preprint

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Associated with Type 2 diabetes (T2DM), renal dysfunction contributes to an increased death rate. Consequently, it would appear that preventing the advancement of renal disease is crucial in the treatment of diabetic patients. SGLT2 inhibitors have been linked to reduced renal mortality, decreased hospitalization, and slowed the progression of renal impairment and albuminuria. The objective of this study was aimed to identify natural SGLT2 inhibitors using an in silico evaluation of the compounds of zinc database using structure-based virtual screening. Using pharmacophore modelling of the standard drug, a total of 1,1336 natural compounds that have the potential to act as SGLT2 inhibitors were identified; six of these compounds, 580, 1131, 212, 357, 822, and 306, had a similar docking affinity to the four known SGLT2 inhibitors. The top two finds, 580 and 306, were chosen due to the convenience of the pharmacokinetic characteristics from the absorption, distribution, metabolism and excretion (ADME), oral bioavailability, and parameters from molecular dynamics simulation (MD). Compound 580 was discovered as a potential treatment candidate after estimations of the metabolic processes and cardiotoxicity. This study may assist in the advancement of both in vitro and in vivo validation, as well as the development of new SGLT2 inhibitors.

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