Novel Dibenzoazepine-Substituted Triazole Hybrids as Cholinesterase and Carbonic Anhydrase Inhibitors and Anticancer Agents: Synthesis, Characterization, Biological Evaluation, and In Silico Studies

ACS Omega, Journal Year: 2024, Volume and Issue: 9(47), P. 46860 - 46878

Published: Nov. 16, 2024

The new dibenzoazepine-substituted triazole hybrids (12–20) were designed by molecular hybridization approach and synthesized utilizing the Cu(I)-catalyzed click reaction. hybrid structures obtained in high yields (74–98%) with a simple two-step synthesis strategy fully characterized. These compounds assessed for their influence on various metabolic enzymes including human carbonic anhydrase isoenzymes (hCA I hCA II), acetylcholinesterase (AChE), butyrylcholinesterase (BChE). Ki values concerning I, II, AChE, BChE ranges 29.94–121.69, 17.72–89.42, 14.09–44.68, 1.15–48.82 nM, respectively. Compound 13 was 49.70-fold more active than tacrine (standard drug) 5.49-fold AChE. 14 4.16-fold acetazolamide 5.79-fold II. cytotoxic effects of products investigated triple-negative breast cancer cell lines. IC50 most effective calculated between 12.51 ± 1.92 18.07 2.14 μM MDA-MB-231 BT-549 cells. Molecular docking ADME predictions performed. Then, vitro analyzed dynamics (MD) simulation MM/GBSA calculation. Consequently, showed good cytotoxicity inhibition potential colony formation

Language: Английский

Synthesis, Characterization and In Silico Studies of Novel (E)-4-(((3-(substituted phenyl)-1-phenyl-1H-pyrazol-5-yl)methylene)amino)benzenesulfonamide as Diuretic Agents

Oriental Journal Of Chemistry, Journal Year: 2024, Volume and Issue: 40(2), P. 413 - 421

Published: April 30, 2024

This research delves into the examination of benzene sulphonamide derivatives featuring pyrazole rings as potential diuretics. Concentrating on their role human carbonic anhydrase inhibitors (hCA), investigation aims to unveil a groundbreaking diuretic drug. Six innovative benzenesulfonamide are synthesized utilizing conventional heating process. Subsequently, employing AutoDock Vina 1.2.3, these compounds undergo molecular docking assessments and pharmacokinetic predictions at active sites hCA I II, while SwissADME program is employed for forecasting. Notably, Compounds 17 19 exhibit robust binding affinities with respectively, evidenced by study. ADME studies reveal favorable bioavailability adherence PAINS alerts, well Lipinski's rule five requirements. Consequently, based findings, significant diuretics in comparison well-established acetazolamide medications.

Language: Английский

Synthesis and biological evaluation of lappaconitine analogues as potential anti-neuroinflammatory agents by side chain modification and scaffold hopping strategy

Bioorganic & Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 117, P. 118012 - 118012

Published: Nov. 20, 2024

Language: Английский