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Anti-tumor metabolites from Synadenium grantii Hook F.

Medicinal Chemistry Research volume 31, pages 666–673 (2022)Cite this article

Abstract

Beta-sitosterol (1) and ingol 7,8,12-triacetate 3-phenylacetate (2) were isolated from leaves of Synadenium grantii Hook F. and screened for anti-tumor activity against a NCI60 cell line panel. The highly functionalized ingol diterpene (2) displayed cytotoxicity against leukemia cancer cells (SR) and renal cancer cells (CAKI-1) with growth inhibition of 33% and 21%, respectively. Since PIK3α inhibitors are predicted to target PI3K/Akt signaling that is operative in renal cancer and leukemia, in silico molecular docking simulations with an alpha isoform of PIK3 were performed. Docking simulations confirmed that 2 fits in the active site with a docking score of −9.03 kcal/mol. Computational modeling included biological validation against the enzyme target, PI3KCα based on the commercial inhibitors X6K and GDC-0326 with experimental IC50 values of 18 and 0.2 nM, respectively. Ingol diterpene (2), isolated from the medicinal herb S. grantii, holds potential as an inhibitor for select tumors; binding simulations indicate possible inhibition via the PI3K/Akt signaling pathway.

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Authors and Affiliations

  1. Key Laboratory of Biotechnology of Chinese Traditional Medicine, Hubei University, National and Local Joint Engineering Research Center of High-throughput Drug Screening Technology, Wuhan, 430062, China

    Lujun Li

  2. Department of Chemistry & Biochemistry, Texas Tech University, Lubbock, TX, 79409, USA

    Qingya Zou, Jayendra Chunduru, Nicholas Laroe & Paul W. Paré

  3. Computational Chemistry Laboratory, Chemistry Department, Faculty of Science, Minia University, Minia, Egypt

    Mahmoud A. A. Ibrahim

  4. Chemistry of Medicinal Plants Department, National Research Centre, Giza, 12622, Egypt

    Emad M. Hassan & Mohamed-Elamir F. Hegazy

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  1. Lujun Li
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Li, L., Zou, Q., Chunduru, J. et al. Anti-tumor metabolites from Synadenium grantii Hook F.. Med Chem Res 31, 666–673 (2022). https://doi.org/10.1007/s00044-022-02867-1

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