Visible Light-Driven, Solvent-Free Pyranopyrazole Synthesis: Anticancer Potential and Computational ADMET Assessment

A sustainable, catalyst-free and solvent-free method for the synthesis of 1,4-dihydropyrano[2,3-c]pyrazoles was developed using visible blue light-emitting diode (LED) light (24 W) under ambient conditions. The reaction proceeds via an electron donor-acceptor (EDA) complex mechanism, achieving excellent yields (80%-99%) within 30 min without requiring hazardous reagents. Structural characterization of the synthesized compounds (4a-4k and 5a-5k) was confirmed through ¹H NMR, ¹³C NMR, IR, MS and single-crystal x-ray diffraction (XRD). Among them, compound 4a exhibited the most potent anticancer activity with IC₅₀ values of 10.15 µM (MCF-7) and 16.32 µM (MDA-MB-231), comparable to Tamoxifen. In silico ADMET and toxicity predictions further supported its drug-likeness and safety. The protocol was successfully scaled up to gram scale and demonstrated excellent green chemistry metrics, reinforcing its applicability in pharmaceutical synthesis. This approach represents an efficient, eco-friendly and scalable platform for designing biologically active heterocycles aligned with green chemistry principles.