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Volume 34, Issue 2 (March & April 2026)
J Adv Med Biomed Res 2026, 34(2): 193-202 |
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Ali D N, Ahmed A, Al-qaisi A H J. Design and In Vitro Evaluation of Schiff Base-Based Heterocyclic Derivatives as Potential Anticancer Agents Targeting Pancreatic Cancer. J Adv Med Biomed Res 2026; 34 (2) :193-202
URL: http://journal.zums.ac.ir/article-1-7932-en.html
URL: http://journal.zums.ac.ir/article-1-7932-en.html
1- Department of Microbial Biotechnology, College of Biotechnology AL-Nahrain University, Jadriga, Baghdad, Iraq , dina.naseer@nahrainuniv.edu.iq
2- Chemistry Department, College of Science, Al-Nahrain University, Baghdad, Iraq
2- Chemistry Department, College of Science, Al-Nahrain University, Baghdad, Iraq
Abstract: (368 Views)
Background & Objective: Pancreatic cancer is characterized by its highly aggressive nature, necessitating the development of innovative chemotherapeutic agents with enhanced selectivity and efficacy. To synthesize and biologically evaluate these Schiff base derivatives as potential anticancer agents against pancreatic cancer by assessing their cytotoxicity, selectivity, and mechanisms of apoptosis induction 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 a dose-dependent inhibition of cell proliferation across all compounds. Derivative D4 exhibited superior selectivity for cancer cells, with IC50_{50}50 values of 129.5 μmuμg/mL for PANC-1 and 237.4 μmuμg/mL for HDFn cells. In contrast, derivative D5 displayed higher overall cytotoxicity but lower selectivity (IC50_{50}50 = 68.9 and 61.01 μmuμg/mL for PANC-1 and HDFn cells, respectively). High-content screening revealed that D4 treatment reduced viable cell counts and mitochondrial membrane potential, attributed to increased nuclear intensity and membrane permeability. Furthermore, significant activation of Caspase-8 and Caspase-9 was observed at 100 and 200 μmuμg/mL (P=0.0019P = 0.0019P=0.0019 and P<0.0001P < 0.0001P<0.0001, respectively), indicating the induction of both intrinsic and extrinsic 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.
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 a dose-dependent inhibition of cell proliferation across all compounds. Derivative D4 exhibited superior selectivity for cancer cells, with IC50_{50}50 values of 129.5 μmuμg/mL for PANC-1 and 237.4 μmuμg/mL for HDFn cells. In contrast, derivative D5 displayed higher overall cytotoxicity but lower selectivity (IC50_{50}50 = 68.9 and 61.01 μmuμg/mL for PANC-1 and HDFn cells, respectively). High-content screening revealed that D4 treatment reduced viable cell counts and mitochondrial membrane potential, attributed to increased nuclear intensity and membrane permeability. Furthermore, significant activation of Caspase-8 and Caspase-9 was observed at 100 and 200 μmuμg/mL (P=0.0019P = 0.0019P=0.0019 and P<0.0001P < 0.0001P<0.0001, respectively), indicating the induction of both intrinsic and extrinsic 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.
Keywords: Pancreatic Neoplasms, Cytotoxicity, Schiff Bases, Heterocyclic Compounds, Apoptosis, Caspase Activation
Type of Study: Original Research Article |
Subject:
Life Science
Received: 2025/12/8 | Accepted: 2026/05/11 | Published: 2026/05/20
Received: 2025/12/8 | Accepted: 2026/05/11 | Published: 2026/05/20
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