Physicochemical properties, drug likeness, ADMET, DFT studies, and in vitro antioxidant activity of oxindole derivatives
| dc.contributor.author | Goncagül Serdaroğlu | |
| dc.date.accessioned | 2024-03-08T05:03:20Z | |
| dc.date.available | 2024-03-08T05:03:20Z | |
| dc.date.issued | 2023 | tr |
| dc.department | Eğitim Fakültesi | tr |
| dc.description.abstract | Poor pharmacokinetic and safety profiles create significant hurdles in the drug development process. This work focuses on a detailed understanding of drug discovery interplay among physicochemical, pharmacokinetic, toxicity endpoints, and antioxidant properties of oxindole derivatives. DFT compıutations were also performed at B3LYP/6-311G** level to evaluate the physicochemical properties, global reactivity features, and intramolecular interactions. The BOILED-Egg pharmacokinetic model envisaged gastrointestinal absorption, blood-brain barrier penetration, and no interaction with p-glycoprotein for compounds C1 and C2. The physicochemical evaluation revealed that C1 possesses superior drug-like properties fit for oral absorption. Both derivatives were predicted to have high plasma protein binding, efficient distribution, and inhibiting CYP 450 major isoforms but serve as substrates only for a few of them. Both molecules have mild to moderate clearance rates. Out of ten toxicity parameters, only hepatotoxicity was predicted. DFT results implied that the meta position of the -OH group made the possibility of charge transfer greater than -para positioned -OH, due to the ΔNmax (eV) values of molecules C1 and C2 being calculated at 2.596 and 2.477, respectively. Both C1 and C2 exhibited a concentration dependant DPPH and ABTS radical scavenging activity. The chemical structure-physicochemical-pharmacokinetic relationship identified the meta position as the favorite for the electron-withdrawing hydroxyl group. This provides useful insight to medicinal chemists to design 6-chlorooxindole derivatives with an acceptable drug-like and pharmacokinetic property. | tr |
| dc.identifier.doi | 10.1016/j.compbiolchem.2023.107861 | en_US |
| dc.identifier.endpage | 107861 | tr |
| dc.identifier.issue | 1 | tr |
| dc.identifier.pmid | 37060784 | en_US |
| dc.identifier.scopus | 2-s2.0-85152238515 | en_US |
| dc.identifier.scopusquality | N/A | |
| dc.identifier.startpage | 107861 | tr |
| dc.identifier.uri | https://www.sciencedirect.com/science/article/pii/S147692712300052X?via%3Dihub | |
| dc.identifier.uri | https://hdl.handle.net/20.500.12418/14982 | |
| dc.identifier.volume | 104 | tr |
| dc.identifier.wos | WOS:000983800000001 | en_US |
| dc.identifier.wosquality | Q2 | |
| dc.indekslendigikaynak | Web of Science | en_US |
| dc.indekslendigikaynak | Scopus | en_US |
| dc.indekslendigikaynak | PubMed | en_US |
| dc.language.iso | en | en_US |
| dc.publisher | Elsevier | tr |
| dc.relation.ispartof | Computational Biology and Chemistry | en_US |
| dc.relation.publicationcategory | Uluslararası Hakemli Dergide Makale - Kurum Öğretim Elemanı | tr |
| dc.rights | info:eu-repo/semantics/openAccess | tr |
| dc.title | Physicochemical properties, drug likeness, ADMET, DFT studies, and in vitro antioxidant activity of oxindole derivatives | en_US |
| dc.type | Article | en_US |
