Design and synthesis of novel benzimidazole-based hydrazones as potential gastroprotective agents: Antioxidant, histopathological, and structure–activity relationship studies in an ethanol-induced gastric ulcer rat model
4 affiliations
- 1Department of Organic Chemistry, Faculty of Chemistry, University of Mazandaran, Babolsar, Iran; Department of Biology, College of Education for Pure Science, University of Kerbala, Karbala, Iraq
- 2Department of Organic Chemistry, Faculty of Chemistry, University of Mazandaran, Babolsar, Iran; Corresponding authors at: Department of Organic Chemistry, Faculty of Chemistry, University of Mazandaran, Babolsar 47416-95447, Iran.
- 3College of Medicine, University of Al-Ameed, Karbala, Iraq
- 4Department of Chemistry, College of Education for Pure Science, University of Kerbala, Karbala, Iraq
Abstract
Peptic ulcer disease continues to be a significant gastrointestinal condition, underscoring the necessity for safer and more effective gastroprotective agents that possess antioxidant properties. In this research, a novel series of benzimidazole-based hydrazone derivatives ( SH1–SH11 ) were designed, synthesized, and assessed for their gastroprotective potential against ethanol-induced gastric ulcers. The target compounds were synthesized through a multistep synthetic process and characterized using melting point determination, FT-IR, 1 H NMR, and 13 C NMR spectroscopy. The gastroprotective activity was evaluated in albino rats utilizing an ethanol-induced gastric ulcer model. The areas of gastric lesions were quantified using ImageJ software, followed by histopathological analysis and biochemical assessment of serum superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) levels. The synthesized derivatives displayed biological activities that were dependent on their structure. Among these, SH1 exhibited the highest gastroprotective efficacy, comparable to that of omeprazole, demonstrating a significant reduction in gastric lesions and considerable preservation of gastric mucosal architecture. Furthermore, SH1 notably restored antioxidant enzyme activities by elevating SOD and CAT levels while decreasing MDA, which indicates a reduction in oxidative stress. The structure–activity relationship (SAR) analysis revealed that the characteristics of the aldehyde-derived substituent had a substantial impact on biological activity, with substituted aromatic derivatives generally showing superior performance compared to their heteroaromatic counterparts. Molecular docking analysis of SH1, SH2, and SH11 provided additional insights into their predicted interactions with the investigated biological target, although the docking scores did not completely parallel the experimentally observed gastroprotective activities. The obtained results suggest that attenuation of systemic oxidative stress may contribute to the observed gastroprotective effects of these derivatives. These findings position SH1 as a promising lead compound for the advancement of new benzimidazole-based gastroprotective agents.
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BibTeX
@article{shwayekh2026design,
title = {{Design and synthesis of novel benzimidazole-based hydrazones as potential gastroprotective agents: Antioxidant, histopathological, and structure–activity relationship studies in an ethanol-induced gastric ulcer rat model}},
author = {Shatha AbdulJabbar Ismael Shwayekh and Heshmatollah Alinezhad and Mahmood Tajbakhsh and Abdul Amir H. Kadhum and Ammar Abdul-Hussein Awad},
journal = {Results in Chemistry},
year = {2026},
month = oct,
doi = {10.1016/j.rechem.2026.103997},
url = {https://doi.org/10.1016/j.rechem.2026.103997},
note = {CC BY},
}
RIS
TY - JOUR
TI - Design and synthesis of novel benzimidazole-based hydrazones as potential gastroprotective agents: Antioxidant, histopathological, and structure–activity relationship studies in an ethanol-induced gastric ulcer rat model
AU - Shatha AbdulJabbar Ismael Shwayekh
AU - Heshmatollah Alinezhad
AU - Mahmood Tajbakhsh
AU - Abdul Amir H. Kadhum
AU - Ammar Abdul-Hussein Awad
PY - 2026
DA - 2026/10/30
JO - Results in Chemistry
DO - 10.1016/j.rechem.2026.103997
UR - https://doi.org/10.1016/j.rechem.2026.103997
AB - Peptic ulcer disease continues to be a significant gastrointestinal condition, underscoring the necessity for safer and more effective gastroprotective agents that possess antioxidant properties. In this research, a novel series of benzimidazole-based hydrazone derivatives ( SH1–SH11 ) were designed, synthesized, and assessed for their gastroprotective potential against ethanol-induced gastric ulcers. The target compounds were synthesized through a multistep synthetic process and characterized using melting point determination, FT-IR, 1 H NMR, and 13 C NMR spectroscopy. The gastroprotective activity was evaluated in albino rats utilizing an ethanol-induced gastric ulcer model. The areas of gastric lesions were quantified using ImageJ software, followed by histopathological analysis and biochemical assessment of serum superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) levels. The synthesized derivatives displayed biological activities that were dependent on their structure. Among these, SH1 exhibited the highest gastroprotective efficacy, comparable to that of omeprazole, demonstrating a significant reduction in gastric lesions and considerable preservation of gastric mucosal architecture. Furthermore, SH1 notably restored antioxidant enzyme activities by elevating SOD and CAT levels while decreasing MDA, which indicates a reduction in oxidative stress. The structure–activity relationship (SAR) analysis revealed that the characteristics of the aldehyde-derived substituent had a substantial impact on biological activity, with substituted aromatic derivatives generally showing superior performance compared to their heteroaromatic counterparts. Molecular docking analysis of SH1, SH2, and SH11 provided additional insights into their predicted interactions with the investigated biological target, although the docking scores did not completely parallel the experimentally observed gastroprotective activities. The obtained results suggest that attenuation of systemic oxidative stress may contribute to the observed gastroprotective effects of these derivatives. These findings position SH1 as a promising lead compound for the advancement of new benzimidazole-based gastroprotective agents.
SN - 2211-7156
ER -