Glioma, particularly its most malignant form, glioblastoma multiforme (GBM), is the most common and aggressive malignant central nervous system tumor. The drawbacks of the current chemotherapy for GBM have aroused curiosity in the search for targeted therapies. Aberrantly overexpressed epidermal growth factor receptor (EGFR) in GBM results in poor prognosis, low survival rates, poor responses to therapy and recurrence, and therefore EGFR-targeted therapy stands out as a promising approach for the treatment of gliomas. In this context, a series of pentacyclic triterpene analogues were subjected to in vitro and in silico assays, which were conducted to assess their potency as EGFR-targeted anti-glioma agents. In particular, compound 10 was the most potent anti-glioma agent with an IC50 value of 5.82 µM towards U251 human glioblastoma cells. Taking into account its low cytotoxicity to peripheral blood mononuclear cells (PBMCs), compound 10 exerts selective antitumor action towards Jurkat human leukemic T-cells. This compound also induced apoptosis and inhibited EGFR with an IC50 value of 9.43 µM compared to erlotinib (IC50 = 0.06 µM). Based on in vitro and in silico data, compound 10 stands out as a potential orally bioavailable EGFR-targeted anti-glioma agent endowed with the ability to cross the blood–brain barrier (BBB).
A novel hybrid ligand, a vic‐dioxime ligand (ETO), containing thiosemicarbazone and egonol moieties from a natural plant (Styrax officinalis) and its trinuclear [Ni(II), Cu(II), Co(II), and Fe(II)] and mononuclear [Pd(II) and Zn(II)] complexes have been synthesized and characterized. The ligand, complexes, and natural components were characterized by conventional spectroscopic techniques (IR, NMR, and MS) and evaluated against two human cancer cell lines (MCF‐7 and PC‐3) to determine their antiproliferative and apoptotic properties. Apoptotic or necrotic effects were detected in both cancer cell lines using the Hoechst/propidium iodide double‐staining method. Paclitaxel was used as a positive control (1 μM). The results displayed that the compounds obtained in this study were effective in the concentration range of 5–40 μM in prostate and breast cancer cell lines. It can be said that the compounds (egonol, its derivatives, hybrid ligand, and its metal complexes) are mostly more effective in PC‐3 migration lines. Consequently, the cytotoxic efficiencies of [Cu3(ETO)2·4Cl], 5.27 μM for MCF‐7 and 13.44 μM for PC‐3 and [Zn (ETO)·2Cl] 11.73 μM for MCF‐7 and 9.32 μM for PC‐3 were observed to be close to paclitaxel (a drug used as a cancer chemotherapeutic agent). [Cu3(ETO)2·4Cl] were more effective on the MCF‐7 cell line. Besides this result, [Zn (ETO)·2Cl] was more effective on the PC‐3 cell lines and was more effective by triggering apoptosis in the cells.
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