Discovery and synthesis of novel magnolol derivatives with potent anticancer activity in non-small cell lung cancer

European Journal of Medicinal Chemistry
Huan TangLijuan Chen

Abstract

EGFR T790 M accounts for 50% to 60% of cases of non-small-cell lung carcinoma (NSCLC) resistance to the first-generation EGFR tyrosine kinase inhibitors (TKIs). Hence, identifying novel compounds with activity against TKIs resistant is of great value. In this study, twenty honokiol and magnolol derivatives were isolated from the EtOH extract of Magnolia officinalis and the antiproliferative activity was evaluated on HCC827 (19del EGFR mutation), H1975 (L858 R/T790 M EGFR mutation), and H460 (KRAS mutation) cell lines. Among the isolated compounds, piperitylmagnolol (a 3-substituted magnolol derivative) showed the best antiproliferative activity against those three cell lines with the IC50 values of 15.85, 15.60 and 18.60 μM, respectively, which provided a direction for the structural modification of magnolol. Further structural modification led to the synthesis of thirty-one magnolol derivatives, and compounds A13, C1, and C2 exhibited significant and broad-spectrum antiproliferative activity with the IC50 values ranging from 4.81 to 13.54 μM, which were approximately 4- and 8-fold more potent than those of honokiol and magnolol, respectively. Moreover, their aqueous solubility was remarkably improved with 12-, 400- and 105 fol...Continue Reading

Citations

Apr 30, 2020·Investigative Ophthalmology & Visual Science·Lu ZhanGuiqiu Zhao
Aug 5, 2019·Current Drug Targets·Yangyang ZhangXiukun Lin
Mar 9, 2021·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Mustafa Ergul, Filiz Bakar-Ates
Jul 25, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Xiao-Long SunCheng-Zhu Wu
Jul 25, 2021·International Journal of Molecular Sciences·Joanna Skopinska-WisniewskaJustyna Kozlowska

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