Synthetic optimization using RuPhos PdG4 catalyst in Suzuki–Miyaura coupling reaction and bio-evaluation of 1,3,4-Oxadiazole derivatives as potential lung cancer agents

1,3,4-Oxadiazole is a well-recognized scaffold in medicinal chemistry due to its broad spectrum of biological activities. In this study, we report an efficient RuPhos Pd G4-catalyzed Suzuki–Miyaura cross-coupling methodology for functionalizing 1,3,4-oxadiazole substrates. The developed protocol offers high yields, clean reactions, a broad substrate scope, and is amenable to gram-scale synthesis. This approach provides facile access to novel, biologically relevant derivatives suitable for further pharmacological exploration. The structures of all synthesized compounds were confirmed using standard spectroscopic techniques, including 1 H NMR, 13 C NMR, and HRMS. Selected compounds ( 1b, 1c, 1f , and 1q ) were subjected to molecular docking studies against the protein target with PDB ID: 3OW4 . These four compounds were also evaluated for their cytotoxic effects against A549 lung cancer cell lines, where compound 1c exhibited the most favorable docking score (−7.296), indicating favorable binding affinity and demonstrated highest cytotoxic effect, with an IC₅₀ value of 28.49 μM. This methodology offers a valuable tool for the synthesis of structurally diverse oxadiazole derivatives with the optimization conditions and the use of RuPhos PdG4 offers a distinct advantage over conventional palladium catalysts due to its enhanced catalytic activity, high functional group tolerance, and efficient performance under mild reaction conditions. The promising biological activity of compound 1c suggests its potential as a lead compound for the development of novel therapeutic agents targeting lung cancer.