Novel Thiochroman‐4‐One Derivatives Bearing a Sulfonyl Hydrazone Moiety: Synthesis, Bioactivity, Molecular Simulation, and Drug‐Likeness Evaluation
- 1College of Life and Health Science Kaili University Kaili China
- 2Guizhou Key Laboratory of Miao Medicine, Qiandongnan Engineering and Technology Research Center for Comprehensive Utilization of National Medicine Kaili University Kaili China
Abstract
Herein, a series of novel thiochroman‐4‐one derivatives bearing sulfonyl hydrazone moiety were rationally designed and synthesized via molecular hybridization strategy. The sulfonyl hydrazone pharmacophore with excellent hydrogen‐bonding interaction ability was first introduced into the thiochroman‐4‐one parent skeleton to construct dual‐active functional molecules, aiming to achieve synergistic α‐glucosidase inhibition and antioxidant activity for antidiabetic therapy. All target compounds were structurally characterized by 1H NMR, 1 3C NMR, and HRMS. Bioactivity results showed that multiple derivatives exhibited excellent α‐glucosidase inhibitory activity and antioxidant capacity, among which compound 5k displayed the optimal comprehensive pharmacological performance with IC50 value of 4.57 µg/mL against α‐glucosidase, which was significantly superior to the positive control acarbose (237.48 µg/mL). Molecular docking and molecular dynamics (MD) simulation verified that the optimal compound 5k could stably bind to the active pocket of α‐glucosidase through multiple hydrogen bonds and hydrophobic interactions, with lower binding energy and better complex stability. Drug‐likeness evaluation demonstrated that all synthesized derivatives complied with Lipinski's rule of five and had favorable pharmacokinetic properties. This work provides a novel structural scaffold for the development of high‐efficiency antioxidant, α‐glucosidase, and antibacterial inhibitors, and demonstrates its potential as a lead compound for pharmaceutical and agrochemical development.
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BibTeX
@article{li2026novel,
title = {{Novel Thiochroman‐4‐One Derivatives Bearing a Sulfonyl Hydrazone Moiety: Synthesis, Bioactivity, Molecular Simulation, and Drug‐Likeness Evaluation}},
author = {Pei Li and Wenming Pan and Tiantian Zhuang and Xiang Wang},
journal = {Chemistry \& Biodiversity},
year = {2026},
month = oct,
doi = {10.1002/cbdv.71884},
url = {https://doi.org/10.1002/cbdv.71884},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Novel Thiochroman‐4‐One Derivatives Bearing a Sulfonyl Hydrazone Moiety: Synthesis, Bioactivity, Molecular Simulation, and Drug‐Likeness Evaluation
AU - Pei Li
AU - Wenming Pan
AU - Tiantian Zhuang
AU - Xiang Wang
PY - 2026
DA - 2026/10/27
JO - Chemistry & Biodiversity
DO - 10.1002/cbdv.71884
UR - https://doi.org/10.1002/cbdv.71884
AB - Herein, a series of novel thiochroman‐4‐one derivatives bearing sulfonyl hydrazone moiety were rationally designed and synthesized via molecular hybridization strategy. The sulfonyl hydrazone pharmacophore with excellent hydrogen‐bonding interaction ability was first introduced into the thiochroman‐4‐one parent skeleton to construct dual‐active functional molecules, aiming to achieve synergistic α‐glucosidase inhibition and antioxidant activity for antidiabetic therapy. All target compounds were structurally characterized by 1H NMR, 1 3C NMR, and HRMS. Bioactivity results showed that multiple derivatives exhibited excellent α‐glucosidase inhibitory activity and antioxidant capacity, among which compound 5k displayed the optimal comprehensive pharmacological performance with IC50 value of 4.57 µg/mL against α‐glucosidase, which was significantly superior to the positive control acarbose (237.48 µg/mL). Molecular docking and molecular dynamics (MD) simulation verified that the optimal compound 5k could stably bind to the active pocket of α‐glucosidase through multiple hydrogen bonds and hydrophobic interactions, with lower binding energy and better complex stability. Drug‐likeness evaluation demonstrated that all synthesized derivatives complied with Lipinski's rule of five and had favorable pharmacokinetic properties. This work provides a novel structural scaffold for the development of high‐efficiency antioxidant, α‐glucosidase, and antibacterial inhibitors, and demonstrates its potential as a lead compound for pharmaceutical and agrochemical development.
SN - 1612-1872
SN - 1612-1880
ER -