Investigation of Newly Synthesized Fluorinated Isatin-Hydrazones by In Vitro Antiproliferative Activity, Molecular Docking, ADME Analysis, and e-Pharmacophore Modeling

ACS Omega, Journal Year: 2024, Volume and Issue: 9(24), P. 26503 - 26518

Published: June 5, 2024

In this study, we investigated the in vitro antiproliferative activities and performed computational studies of newly synthesized fluorinated isatin-hydrazones. The chemical structures compounds were confirmed by FT-IR, 1D NMR (1H- 13C APT), 2D (HETCOR HMBC), elemental analysis. All (1–15) tested human lung (A549) liver (HepG2) cancer cell lines for 72 h. screened against a healthy embryonic kidney line (HEK-293T) under same conditions to determine their toxic effects. According results obtained, one compounds, particular, compound 8 was effective at inhibiting growth cancerous cells, its effects on both similar IC50 values 42.43 48.43 μM A549 HepG2, respectively. Compound 8, which determined be best anticancer agent vitro, chosen interact with target via molecular docking. This selected ligand (compound 8) interacted targets 4HJO, 4ASD, 3POZ, 7TZ7, docked into active sites. docking score, Glide energy, emodel calculated lower than those reference cisplatin. pharmacokinetic properties, stability, drug-likeness parameters all designed estimated using SwissADME. Finally, binding affinities four MM-GBSA method.

Language: Английский

New Sulfonate Ester‐Linked Fluorinated Hydrazone Derivatives as Multitarget Carbonic Anhydrase and Cholinesterase Inhibitors: Design, Synthesis, Biological Evaluation, Molecular Docking and ADME Analysis

Chemistry & Biodiversity, Journal Year: 2024, Volume and Issue: 21(12)

Published: Aug. 19, 2024

Abstract In this study, some new hydrazone derivatives ( 2a – g ) was designed, synthesized for first time, and evaluated as multitarget inhibitors of AChE, BChE, hCA I II. The chemical structures hybrids were confirmed by elemental analysis spectroscopic techniques. All tested compounds showed low nanomolar inhibition with IC 50 values in the range 30.4–264.0 nM against I, 23.2–251.6 II, 12.1–114.3 76.4–134.0 BChE. These inhibited AChE more than acetazolamide (AZA) neostigmine. Among them, 2c 2e , which have a linear structure, determined to be most active inhibitor candidates these selected enzymes. Molecular docking studies carried out on 2a‐ ‐ ), revealing their binding interactions site II thus supporting experimental findings. Additionally, silico absorption, distribution, metabolism, excretion (ADME) prediction obtained approaches determine solubility, whether they potential cross blood‐brain barrier (BBB), such GI absorption drug likeness principles.

Language: Английский

Synthesis of Novel Cu(II), Co(II), Fe(II), and Ni(II) Hydrazone Metal Complexes as Potent Anticancer Agents: Spectroscopic, DFT, Molecular Docking, and MD Simulation Studies

ACS Omega, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 10, 2024

Metal complexes [FeL], [NiL]·H