en Life Science Life Science مقاله پژوهشی Original Research Article <span style="font-size:16px;"><span style="font-family:Times New Roman;"><span new="" roman="" times=""><b><span style="background:#2d7f8f"><span style="color:white">Background & Objective:</span></span></b><b> </b><b>&nbsp;</b><span lang="EN"><span style="color:black">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 <i>in vitro</i>.</span></span></span><br> <span new="" roman="" times=""><b>&nbsp;</b><b><span lang="EN-IN"><span style="background:#2d7f8f"><span style="color:white"><span style="letter-spacing:-.1pt">Materials & Methods:</span></span></span></span></b> &nbsp;<span lang="EN"><span style="color:black"><span style="letter-spacing:-.1pt">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 <i>in vitro</i> against PANC-1 (pancreatic cancer) and HDFn (normal human dermal fibroblast) cell lines.</span></span></span></span><br> <span new="" roman="" times=""><b><span lang="EN-IN"><span style="background:#2d7f8f"><span style="color:white">Results: </span></span></span></b><b>&nbsp;</b><span lang="EN"><span style="color:black"><span style="letter-spacing:-.1pt">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 &mu;mu&mu;g/mL for PANC-1 and 237.4 &mu;mu&mu;g/mL for HDFn cells. In contrast, derivative D5 displayed higher overall cytotoxicity but lower selectivity (IC50_{50}50​ = 68.9 and 61.01 &mu;mu&mu;g/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 &mu;mu&mu;g/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.</span></span></span></span><br> <span new="" roman="" times=""><b><span style="background:#2d7f8f"><span style="color:white">Conclusion: </span></span></b><b>&nbsp;</b><span lang="EN"><span style="color:black">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.</span></span></span><br> &nbsp;</span></span> Pancreatic Neoplasms, Cytotoxicity, Schiff Bases, Heterocyclic Compounds, Apoptosis, Caspase Activation 193 202 http://journal.zums.ac.ir/browse.php?a_code=A-10-7470-1&slc_lang=en&sid=1 Dina Naseer Ali dina.naseer@nahrainuniv.edu.iq 5200319475328460090104 0009-0007-4464-1466 Yes Department of Microbial Biotechnology, College of Biotechnology AL-Nahrain University, Jadriga, Baghdad, Iraq Ahmed Ahmed AhmedAhmed@gmail.com 5200319475328460090105 5200319475328460090105 No Chemistry Department, College of Science, Al-Nahrain University, Baghdad, Iraq Alaa Hussein J. Al-qaisi AlaaHussein@gmail.com 5200319475328460090106 5200319475328460090106 No Chemistry Department, College of Science, Al-Nahrain University, Baghdad, Iraq