Identification of honokiol‐based scaffold to design tankyrase 1/2 inhibitors by in silico and in vitro studies

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Recently, we identified magnolol bioinspired derivatives as new Tankyrase 1/2 (TNKS1/2) inhibitors by our Inverse Virtual Screening protocol. Based on these findings, in the present contribution, we enlarged our investigation of neolignans to the natural product honokiol (1) and a group of its analogues (2–8). By integrating in silico analysis and Surface Plasmon Resonance experiments, we demonstrated the binding of 1 (honokiol), 2, 6 and 7 towards TNKS2. Furthermore, we also proved the binding specificity of 1 and 7 against TNKS2, while 2 and 6 were found to be also TNSK1 binders, along with 4. Promising antiproliferative activity in A549 cancer cell line were observed for 1 and 6, with honokiol (1) presenting a higher potency than the well‐known TNKS2 inhibitor XAV939. Collectively, these outcomes suggest that the honokiol‐based scaffold can be employed to design novel anti‐cancer therapeutic agents.