Rational design and synthesis of furan-based Schiff base quinazolin-4-amine hybrids: spectral elucidation, molecular docking, DFT studies, and in silico ADMET-antioxidant study.
- 1Department of Chemistry, Krishna School of Science, Drs. Kiran & Pallavi Patel Global University (KPGU) Vadodara Gujarat India [email protected].
- 2Department of Chemistry, Shri M. P. Pandya Science College, Shri Govind Guru University Lunawada, Mahisagar Godhra Gujarat India.
Abstract
In this work, a new series of furan-based quinazoline-4-amine hydrazone (Schiff base) derivatives (4a-h) was rationally designed and synthesized in good yields (84-90%) through a multistep route involving nucleophilic aromatic substitution, Suzuki-Miyaura cross-coupling, and hydrazone/Schiff base condensation reactions. The synthesized compounds were characterized by FT-IR, ¹H NMR, ¹³C NMR, and ESI-mass spectrometry, which confirmed the proposed structures. Density functional theory (DFT) calculations were performed to optimize the molecular geometries and to derive frontier molecular orbital energies, global reactivity descriptors, Mulliken atomic charges, and molecular electrostatic potential (MEP) surfaces, providing insight into the stability, reactivity, and radical-scavenging propensity of the compounds. Molecular docking studies against the Kelch domain of Keap1 (PDB 4L7B), the principal negative regulator of the Nrf2-mediated antioxidant response, were carried out using the Schrödinger Suite (Glide, Maestro interface) to explore, in silico, a possible interaction of the derivatives with this target; the docked compounds gave Glide docking scores of -7.325 to -8.603 kcal mol; these results constitute an in silico hypothesis of Keap1 binding that remains to be tested experimentally. Computational ADMET profiling indicated drug-like physicochemical properties overall, with the dimethoxy- and phenolic-substituted analogues 4e and 4h showing the most favourable predicted oral bioavailability (score = 0.55) among the series. The in vitro antioxidant potential of compounds 4a-h was evaluated using the DPPH radical-scavenging assay, giving IC₅₀ values of 85.5 ± 3.7 to 148.1 ± 3.2 µM, compared with 235.2 ± 4.6 µM for the standard antioxidant ascorbic acid; on a molar basis, all eight derivatives were therefore more potent than ascorbic acid in this cell-free assay. Among the series, compounds 4d and 4f displayed the most promising radical-scavenging activity (IC₅₀ = 85.5 and 90.8 µM, respectively), although the global DFT reactivity descriptors did not correlate with the measured activity across the series.
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BibTeX
@article{narode2026rational,
title = {{Rational design and synthesis of furan-based Schiff base quinazolin-4-amine hybrids: spectral elucidation, molecular docking, DFT studies, and in silico ADMET-antioxidant study.}},
author = {Sunil D Narode and Miral Vora and Jay B Maheta and Yogesh O Bhola and Darshna K Lakhnotra and Nikita J Patel},
journal = {RSC advances},
year = {2026},
month = oct,
doi = {10.1039/d6ra08647k},
url = {https://europepmc.org/article/MED/42904125},
note = {CC BY},
}
RIS
TY - JOUR
TI - Rational design and synthesis of furan-based Schiff base quinazolin-4-amine hybrids: spectral elucidation, molecular docking, DFT studies, and in silico ADMET-antioxidant study.
AU - Sunil D Narode
AU - Miral Vora
AU - Jay B Maheta
AU - Yogesh O Bhola
AU - Darshna K Lakhnotra
AU - Nikita J Patel
PY - 2026
DA - 2026/10/20
JO - RSC advances
DO - 10.1039/d6ra08647k
UR - https://europepmc.org/article/MED/42904125
AB - In this work, a new series of furan-based quinazoline-4-amine hydrazone (Schiff base) derivatives (4a-h) was rationally designed and synthesized in good yields (84-90%) through a multistep route involving nucleophilic aromatic substitution, Suzuki-Miyaura cross-coupling, and hydrazone/Schiff base condensation reactions. The synthesized compounds were characterized by FT-IR, ¹H NMR, ¹³C NMR, and ESI-mass spectrometry, which confirmed the proposed structures. Density functional theory (DFT) calculations were performed to optimize the molecular geometries and to derive frontier molecular orbital energies, global reactivity descriptors, Mulliken atomic charges, and molecular electrostatic potential (MEP) surfaces, providing insight into the stability, reactivity, and radical-scavenging propensity of the compounds. Molecular docking studies against the Kelch domain of Keap1 (PDB 4L7B), the principal negative regulator of the Nrf2-mediated antioxidant response, were carried out using the Schrödinger Suite (Glide, Maestro interface) to explore, in silico, a possible interaction of the derivatives with this target; the docked compounds gave Glide docking scores of -7.325 to -8.603 kcal mol; these results constitute an in silico hypothesis of Keap1 binding that remains to be tested experimentally. Computational ADMET profiling indicated drug-like physicochemical properties overall, with the dimethoxy- and phenolic-substituted analogues 4e and 4h showing the most favourable predicted oral bioavailability (score = 0.55) among the series. The in vitro antioxidant potential of compounds 4a-h was evaluated using the DPPH radical-scavenging assay, giving IC₅₀ values of 85.5 ± 3.7 to 148.1 ± 3.2 µM, compared with 235.2 ± 4.6 µM for the standard antioxidant ascorbic acid; on a molar basis, all eight derivatives were therefore more potent than ascorbic acid in this cell-free assay. Among the series, compounds 4d and 4f displayed the most promising radical-scavenging activity (IC₅₀ = 85.5 and 90.8 µM, respectively), although the global DFT reactivity descriptors did not correlate with the measured activity across the series.
SN - 2046-2069
ER -