Design and In Vitro Evaluation of Schiff Base-Based Heterocyclic Derivatives as Potential Anticancer Agents Targeting Pancreatic Cancer.

Background & Objective: Pancreatic cancer is a highly aggressive malignancy that necessitates the development of novel chemotherapeutic agents with improved selectivity and efficacy. This study aimed to synthesize and biologically evaluate a series of Schiff base derivatives as potential anticancer...

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Publicado en:Journal of Advances in Medical & Biomedical Research Vol. 34; no. 2; pp. 193 - 200
Autores principales: Ali, Dina Naseer, Ahmed, Ahmed, Al-qaisi, Alaa Hussein J.
Formato: pictorial research tables/charts Journal Article
Publicado: Zanjan University of Medical Sciences & Health Services Mar/Apr2026
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Mar/Apr2026
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      pub: Zanjan University of Medical Sciences & Health Services
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        atl: Design and In Vitro Evaluation of Schiff Base-Based Heterocyclic Derivatives as Potential Anticancer Agents Targeting Pancreatic Cancer.
      aug:
        au:
          Ali, Dina Naseer
          Ahmed, Ahmed
          Al-qaisi, Alaa Hussein J.
        affil: Department of Microbial Biotechnology, College of Biotechnology, AL-Nahrain University, Jadriga, Baghdad, Iraq.
      sug:
        subj:
          Organic Chemicals Therapeutic Use
          Heterocyclic Compounds Therapeutic Use
          Heterocyclic Compounds Analogs and Derivatives
          Antineoplastic Agents Therapeutic Use
          Pancreatic Neoplasms Drug Therapy
          Apoptosis Drug Effects
          Treatment Outcomes
          Human
          Iraq
          Molecular Structure
          In Vitro Studies
          Experimental Studies
          Caspases
          Cell Cycle
          Indicators and Reagents
          One-Way Analysis of Variance
          Post Hoc Analysis
          Data Analysis Software
          Azepines
          Sulfur Compounds
          Cell Proliferation
      ab: Background & Objective: Pancreatic cancer is a highly aggressive malignancy that necessitates the development of novel chemotherapeutic agents with improved selectivity and efficacy. This study aimed to synthesize and biologically evaluate a series of Schiff base derivatives as potential anticancer agents against pancreatic cancer by assessing their cytotoxicity, selectivity, and ability to induce apoptosis in vitro. Materials & Methods: A different novel heterocyclic derivative, including dihydroquinazoline, oxazepine, tetrazole, and thiazine, were synthesized via a common Schiff base intermediate (Derivative D). The structural characterization of these compounds was performed using FTIR and 1^11H-NMR spectroscopy. To evaluate their therapeutic potential and selectivity, the synthesized derivatives were tested in vitro against PANC-1 (pancreatic cancer) and HDFn (normal human dermal fibroblast) cell lines. Results: MTT assays demonstrated dose-dependent inhibition of cell proliferation by all synthesized compounds. Among them, derivative D4 exhibited greater selectivity toward pancreatic cancer cells, with IC₅₀ values of 129.5 μg/mL for PANC-1 cells and 237.4 μg/mL for HDFn cells. In contrast, derivative D5 showed greater overall cytotoxicity but lower selectivity, with IC₅₀ values of 68.9 μg/mL for PANC-1 cells and 61.0 μg/mL for HDFn cells. High-content screening revealed that D4 treatment significantly reduced the number of viable cells and decreased mitochondrial membrane potential, accompanied by increased nuclear intensity and cell membrane permeability. Furthermore, D4 significantly activated both caspase-8 and caspase-9 at concentrations of 100 and 200 μg/mL (P = 0.0019 and P < 0.0001, respectively), indicating activation of both the extrinsic and intrinsic apoptotic pathways. Conclusion: These findings suggest that the structural optimization of Schiff base-derived heterocycles is a promising strategy for enhancing tumor selectivity and biological safety, potentially offering new avenues for anticancer therapy.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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