Synthesis, Antioxidant Activity, In Silico Evaluation, and Cytotoxicity of Novel Polyphenolic–Methyliden–Hydrazono–Thiazole Derivatives
6 affiliations
- 1Department of Pharmaceutical Chemistry, “Iuliu Hațieganu” University of Medicine and Pharmacy, 41 Victor Babeș Street, 400012 Cluj-Napoca, Romania
- 2Department of Organic Chemistry, “Iuliu Hațieganu” University of Medicine and Pharmacy, 41 Victor Babeș Street, 400012 Cluj-Napoca, Romania
- 3Department of Toxicology, Faculty of Pharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, 8 Victor Babeș, 400012 Cluj-Napoca, Romania
- 4National Institute for Research and Development of Isotopic and Molecular Technologies, 67-103 Donath Street, 400293 Cluj-Napoca, Romania
- 5Department of Pharmaceutical Technology and Biopharmaceutics, “Iuliu Hațieganu” University of Medicine and Pharmacy, 41 Victor Babeș Street, 400012 Cluj-Napoca, Romania
- 6Department of Pharmacognosy, “Iuliu Hațieganu” University of Medicine and Pharmacy, 12 Ion Creangă Street, 400010 Cluj-Napoca, Romania
Abstract
Novel thiazolyl–polyphenolic derivatives were designed and synthesized to investigate the influence of aromatic substituents on antioxidant activity, molecular properties, and cytotoxicity. Eight derivatives (E1–E8) were synthesized by a Hantzsch reaction and their structures were confirmed by MS, FT-IR, and 1H/13C NMR spectroscopy. Antioxidant activity was evaluated using DPPH, ABTS, TAC, RP, FRAP, and CUPRAC assays. The experimental results were supported by DFT calculations and SwissADME prediction, while cytotoxicity was evaluated against A549 lung adenocarcinoma cells and normal BJ fibroblasts. The antioxidant activity depended on the nature of the aromatic substituent. Compound E5 showed a superior antioxidant profile, presenting the highest DPPH radical scavenging activity and the strongest reducing power in the RP assay. The theoretical calculations supported these findings, showing favorable HOMO energy and low O–H bond dissociation energy values. Compound E6 showed the highest activity in the CUPRAC assay and exhibited the strongest cytotoxic activity against A549 cells together with the highest selectivity index. All synthesized compounds complied with Lipinski’s rule of five. Overall, the results show that the electronic properties of the aromatic substituent strongly influence both the antioxidant and cytotoxic activities of this series. These compounds may represent useful scaffolds for further development of antioxidant and anticancer agents.
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BibTeX
@article{cornea2026synthesis,
title = {{Synthesis, Antioxidant Activity, In Silico Evaluation, and Cytotoxicity of Novel Polyphenolic–Methyliden–Hydrazono–Thiazole Derivatives}},
author = {Alexandra Cătălina Cornea and Gabriel Marc and Ionel Fizeșan and Ioana Ionuț and Cristina Moldovan and Anca Stana and Brîndușa Tiperciuc and Ionuț-Valentin Creștin and Adrian Pîrnău and Laurian Vlase and Ilioara Oniga and Ovidiu Oniga},
journal = {Molecules},
year = {2026},
month = oct,
doi = {10.3390/molecules31203620},
url = {https://www.mdpi.com/1420-3049/31/20/3620},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Synthesis, Antioxidant Activity, In Silico Evaluation, and Cytotoxicity of Novel Polyphenolic–Methyliden–Hydrazono–Thiazole Derivatives
AU - Alexandra Cătălina Cornea
AU - Gabriel Marc
AU - Ionel Fizeșan
AU - Ioana Ionuț
AU - Cristina Moldovan
AU - Anca Stana
AU - Brîndușa Tiperciuc
AU - Ionuț-Valentin Creștin
AU - Adrian Pîrnău
AU - Laurian Vlase
AU - Ilioara Oniga
AU - Ovidiu Oniga
PY - 2026
DA - 2026/10/01
JO - Molecules
DO - 10.3390/molecules31203620
UR - https://www.mdpi.com/1420-3049/31/20/3620
AB - Novel thiazolyl–polyphenolic derivatives were designed and synthesized to investigate the influence of aromatic substituents on antioxidant activity, molecular properties, and cytotoxicity. Eight derivatives (E1–E8) were synthesized by a Hantzsch reaction and their structures were confirmed by MS, FT-IR, and 1H/13C NMR spectroscopy. Antioxidant activity was evaluated using DPPH, ABTS, TAC, RP, FRAP, and CUPRAC assays. The experimental results were supported by DFT calculations and SwissADME prediction, while cytotoxicity was evaluated against A549 lung adenocarcinoma cells and normal BJ fibroblasts. The antioxidant activity depended on the nature of the aromatic substituent. Compound E5 showed a superior antioxidant profile, presenting the highest DPPH radical scavenging activity and the strongest reducing power in the RP assay. The theoretical calculations supported these findings, showing favorable HOMO energy and low O–H bond dissociation energy values. Compound E6 showed the highest activity in the CUPRAC assay and exhibited the strongest cytotoxic activity against A549 cells together with the highest selectivity index. All synthesized compounds complied with Lipinski’s rule of five. Overall, the results show that the electronic properties of the aromatic substituent strongly influence both the antioxidant and cytotoxic activities of this series. These compounds may represent useful scaffolds for further development of antioxidant and anticancer agents.
SN - 1420-3049
ER -