Goncagül Serdaroğlu2024-03-082024-03-082023https://www.sciencedirect.com/science/article/pii/S147692712300052X?via%3Dihubhttps://hdl.handle.net/20.500.12418/14982Poor 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.en10.1016/j.compbiolchem.2023.107861info:eu-repo/semantics/openAccessArticle1041107861107861370607842-s2.0-85152238515N/AWOS:000983800000001Q2