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Life sciences · Journal article
Scientific Reports · September 18, 2026
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Abstract Glioblastoma is the most aggressive primary malignant brain tumor in adults. This study examines the anticancer potential of twenty innovative coumarin-based 1,2,4-triazole derivatives, alone and in a combination with paclitaxel, against various human cancer cell lines and in a glioblastoma xenograft model. The cytotoxic effect of 20 new synthesized derivatives was evaluated in four cancerous and two normal human cell lines by MTT assay and cellular uptake of the radiotracer 99m Tc-MIBI. Also, the in vivo antitumor activity of compound 8c was assessed in U87-MG tumor-bearing nude mice through tumor volume measurement and histopathological analysis of tumor and liver tissues. Sulfur-substituted derivatives exhibited greater cytotoxicity against cancer cell lines compared to paclitaxel. Cytotoxicity assay in normal cells revealed derivatives 1a and 1c had higher IC 50 values and lower toxicity than paclitaxel. In the U87-MG cells pre-treated with an IC 50 concentration of derivatives 1a, 1c, 1 h, and 1j, only derivative 1 h showed a significant increase in 99m Tc-MIBI uptake compared to the control group. In-vivo studies demonstrated that compound 1c, both alone and in combination with paclitaxel, significantly suppressed tumor growth compared to the control. Histopathological analysis revealed cell necrosis and tumor cell degeneration particularly in 1c+Paclitaxel group. Moreover, reduced liver toxicity was seen in combination therapy, suggesting a hepatoprotective effect of compound 1c against chemotherapy-induced hepatic injury. 99m Tc-MIBI biodistribution pattern in xenograft models also confirmed these results. These findings suggest that coumarin-based 1,2,4-triazole hybrids containing sulfur moiety could be introduced as anticancer agents with reduced side effects.