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

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Design and synthesis of novel hybrids incorporating thiadiazole or thiazole-naphthalene: Anticancer assessment and molecular docking study

Results in Chemistry, Journal Year: 2024, Volume and Issue: 7, P. 101475 - 101475

Published: Jan. 1, 2024

To underscore the significance of thiazole and thiadiazole moieties in advancing cancer treatment support researchers drug design, we developed a novel series 1,3,4-thiadiazole 1,3-thiazole derivatives. These were synthesized by reacting 2-(naphthalen-1-ylmethylene)-N-phenylhydrazine-1-carbothioamide with hydrazonoyl halides α-halo-compounds. Spectroscopic data alternative syntheses confirmed structures. The growth-inhibitory potential against HepG2-1 liver cells was evaluated using MTT assay, revealing compounds 5c 15 IC50 values 0.53 ± 0.82 0.61 0.72 μM, respectively, demonstrating promising anticancer activity than doxorubicin (IC50 = 0.49 μM). Given high attrition rate development, computational approaches employed to mitigate risks associated poor pharmacokinetics safety. Molecular docking analyses illustrated binding interactions at enzymes' sites, consistent vitro studies, indicating as antitumor agents. In silico investigations affirmed ADMET profile's favorable oral bioavailability properties for compounds. findings highlight investigated ligands candidates further development medicines.

Language: Английский

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Facile one-pot synthesis and in silico study of new heterocyclic scaffolds with 4-pyridyl moiety: Mechanistic insights and X-ray crystallographic elucidation

Heliyon, Journal Year: 2024, Volume and Issue: 10(7), P. e29221 - e29221

Published: April 1, 2024

4-Acetylpyridine

Language: Английский

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Grinding-assisted synthesis of novel arylhydrazono curcumin analogues and bis-pyrazolines as cyclin-dependent kinases (CDKs) inhibitors

Inorganic Chemistry Communications, Journal Year: 2024, Volume and Issue: 169, P. 113128 - 113128

Published: Sept. 6, 2024

Language: Английский

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