Antiproliferative Effects of Pyranopyrazole Analogs: In Vitro and Molecular Docking Analysis

Abstract

Background Glioblastoma multiforme is the most aggressive primary brain tumor in adults, and current multimodal therapies provide only limited survival benefit. There is an urgent need for new small-molecule scaffolds with improved anticancer activity against glioblastoma. Objective To evaluate the antiproliferative effects of pyranopyrazole analogs on human U-87 MG glioblastoma cells and to explore their potential molecular interactions with a glioblastoma-related protein target by molecular docking. Methods A series of pyranopyrazole analogs ( 12a – o ) was synthesized using a previously reported green-chemistry protocol. U-87 MG cells were treated with increasing concentrations of the analogs for 24, 48, and 72 h, and cell viability was measured by a colorimetric tetrazolium-based assay. Half-maximal inhibitory concentration values were determined for the most active analogs and compared with those of a reference chemotherapeutic agent. Molecular docking was performed with the 6c1c protein structure to assess binding energies and interaction profiles. Results Several pyranopyrazole analogs produced dose- and time-dependent cytotoxicity in U-87 MG cells. Analog 12 g showed the strongest antiproliferative effect and lower half-maximal inhibitory concentration values than the reference agent at earlier time points, whereas 12 h , 12o , and 12i displayed moderate activity. Docking analysis indicated favorable binding of active analogs to the 6c1c active site, with multiple hydrogen-bond and π-type interactions involving key residues. Conclusion Pyranopyrazole analogs, particularly 12 g , exhibit promising antiproliferative activity against glioblastoma cells in vitro, supported by compatible molecular docking findings. These compounds may represent useful lead structures for the development of new chemotherapeutic options for glioblastoma. © 2026 The Authors.