Synthesis, characterization, and anticancer evaluation of 1,3-bistetrahydrofuran-2yl-5-FU as a potential agent for pancreatic cancer

The failure of current chemotherapeutic agents for pancreatic cancer (PCa) makes it the most aggressive soft tissue tumor with a 5-year survival of slightly above 10% and is estimated to be the second leading cause of cancer death by 2030. Objective: The main aim was to synthesize, characterize and evaluate the anticancer activity of 1,3-bistetrahydrofuran-2yl-5FU (MFU). Methods: MFU was synthesized by using 5-fluorouracil (5-FU) and tetrahydrofuran acetate, and characterized by nuclear magnetic resonance (NMR), micro-elemental analysis, high-performance liquid chromatography (HPLC), and liquid chromatography with mass spectrophotometry (LC-MS). MFU and Gemcitabine hydrochloride (GemHCl) were tested for antiproliferative activity against MiaPaca-2 and Panc-1 cell lines. Results: The half-minimum inhibitory concentration (IC(50)) of MFU was twice lower than that of GemHCl when used in both cell lines. MiaPaca-2 cells (MFU-IC(50) = 4.5 ± 1.2 μM vs. GemHCl-IC(50) = 10.3 ± 1.1 μM); meanwhile similar trend was observed in Panc-1 cells (MFU-IC(50) = 3.0 ± 1 μM vs. GemHCl-IC(50) = 6.1 ± 1.03 μM). The MFU and GemHCl effects on 3D spheroids showed a similar trend (IC(50-GemHCl) = 14.3 ± 1.1 μM vs. IC(50-MFU) = 7.2 ± 1.1 μM) for MiaPaca-2 cells, and (IC(50-GemHCl) = 16.3 ± 1.1 μM vs. IC(50-MFU) = 9.2 ± 1.1 μM) for Panc-1 cells. MFU significantly inhibited clonogenic cell growth, and induced cell death via apoptosis. Cell cycle data showed mean PI for GemHCl (48.5–55.7) twice higher than MFU (24.7 to 27.9) for MiaPaca-2 cells, and similarly to Panc-1 cells. The in-vivo model showed intensely stained EGFR (stained brown) in all control, GemHCl and MFU-treated mice bearing subcutaneous PDX tumors, however, HER2 expression was less stained in MFU-treated tumors compared to GemHCl-treated tumors and controls. Mean tumor volume of MFU-treated mice (361 ± 33.5 mm(3)) was three-fold lower than GemHCl-treated mice (1074 ± 181.2 mm(3)) bearing pancreatic PDX tumors. Conclusion: MFU was synthesized with high purity and may have potential anticancer activity against PCa. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-022-10449-y.