Discovery of novel vanillin-2-acetylfuran hybrids through integrated design, synthesis, computational studies, and in-vitro cytotoxic evaluation
Abstract
A new one-step, multicomponent Mannich base reaction was developed between vanillin, 2-acetyl furan, and amine derivatives using p-TSA as a catalyst. Synthesized compounds ( 1–26 ) have been characterised using FT-IR, ¹ H NMR, ¹³ C NMR, GC–MS, and elemental analysis. These compounds were evaluated for cytotoxic activity, with doxorubicin as the control. Furthermore, molecular docking, density functional theory, ADME-T, and MD simulations were performed on the synthesized compounds. Compound 14 had a higher binding affinity (-10.3 kcal/mol) than doxorubicin (-7.3 kcal/mol) and other compounds. The pharmacokinetics of the newly synthesised derivatives were predicted using ADME analysis. According to the HOMO–LUMO study, compound 14 had a significant energy gap of 2.77 eV with an energy range of -8.027 eV and -5.258 eV. Simulations of the HER2 receptor (PDB ID: 5NQR) using compound 14 demonstrated stable binding, as evidenced by minimal fluctuations over 100 ns. After docking studies, compound 14 was evaluated for cytotoxicity activity against HepG-2 (IC ₅₀ = 29.07 μg/mL), HeLa (IC 50, = 34.13 μg/mL), and MCF-7 (IC 50, = 25.40 μg/mL) cell lines. Compound 14 was moderately active in MCF-7 (IC 50, = 25.40 μg/mL) compared with other cancer cell lines. In addition to blocking cancer cell invasion, compound 14 promotes apoptosis via mitochondrial-dependent apoptosis and reactive oxygen species (ROS) generation. As a result of the aforementioned findings, vanillin derivatives may suggest useful as anticancer drugs in the future.
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BibTeX
@article{abarna2026discovery,
title = {{Discovery of novel vanillin-2-acetylfuran hybrids through integrated design, synthesis, computational studies, and in-vitro cytotoxic evaluation}},
author = {S. Abarna and D. Sangeetha},
journal = {Scientific Reports},
year = {2026},
month = oct,
doi = {10.1038/s41598-026-66917-z},
url = {https://www.nature.com/articles/s41598-026-66917-z},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Discovery of novel vanillin-2-acetylfuran hybrids through integrated design, synthesis, computational studies, and in-vitro cytotoxic evaluation
AU - S. Abarna
AU - D. Sangeetha
PY - 2026
DA - 2026/10/26
JO - Scientific Reports
DO - 10.1038/s41598-026-66917-z
UR - https://www.nature.com/articles/s41598-026-66917-z
AB - A new one-step, multicomponent Mannich base reaction was developed between vanillin, 2-acetyl furan, and amine derivatives using p-TSA as a catalyst. Synthesized compounds ( 1–26 ) have been characterised using FT-IR, ¹ H NMR, ¹³ C NMR, GC–MS, and elemental analysis. These compounds were evaluated for cytotoxic activity, with doxorubicin as the control. Furthermore, molecular docking, density functional theory, ADME-T, and MD simulations were performed on the synthesized compounds. Compound 14 had a higher binding affinity (-10.3 kcal/mol) than doxorubicin (-7.3 kcal/mol) and other compounds. The pharmacokinetics of the newly synthesised derivatives were predicted using ADME analysis. According to the HOMO–LUMO study, compound 14 had a significant energy gap of 2.77 eV with an energy range of -8.027 eV and -5.258 eV. Simulations of the HER2 receptor (PDB ID: 5NQR) using compound 14 demonstrated stable binding, as evidenced by minimal fluctuations over 100 ns. After docking studies, compound 14 was evaluated for cytotoxicity activity against HepG-2 (IC ₅₀ = 29.07 μg/mL), HeLa (IC 50, = 34.13 μg/mL), and MCF-7 (IC 50, = 25.40 μg/mL) cell lines. Compound 14 was moderately active in MCF-7 (IC 50, = 25.40 μg/mL) compared with other cancer cell lines. In addition to blocking cancer cell invasion, compound 14 promotes apoptosis via mitochondrial-dependent apoptosis and reactive oxygen species (ROS) generation. As a result of the aforementioned findings, vanillin derivatives may suggest useful as anticancer drugs in the future.
SN - 2045-2322
ER -