In silico identification and in vitro validation of nogalamycin N ‐oxide (NSC116555) as a potent anticancer compound against non–small‐cell lung cancer cells
| Autor: | Kiattawee Choowongkomon, Chatchakorn Eurtivong, Kannika Thongkhao, Praphasri Suphakun, Matthew Paul Gleeson, Lueacha Tabtimmai, Phongphat Obounchoey |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Lung Neoplasms Apoptosis In Vitro Techniques Biochemistry Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Gefitinib Carcinoma Non-Small-Cell Lung Tumor Cells Cultured medicine Humans Computer Simulation Epidermal growth factor receptor Cytotoxicity Lung cancer Molecular Biology Cell Proliferation EGFR inhibitors Antibiotics Antineoplastic Molecular Structure biology Kinase Chemistry Nogalamycin Cell Biology medicine.disease ErbB Receptors 030104 developmental biology Docking (molecular) Drug Design 030220 oncology & carcinogenesis Cancer research biology.protein medicine.drug |
| Zdroj: | Journal of Cellular Biochemistry. 120:3353-3361 |
| ISSN: | 1097-4644 0730-2312 |
| Popis: | The epidermal growth factor receptor (EGFR) was found to be overexpressed in several cancers, especially in lung cancers. Finding new effective drug against EGFR is the key to cancer treatment. In this study, the GOLD docking algorithm was used to virtually screen for novel human EGFR inhibitors from the NCI database. Thirty-four hit compounds were tested for EGFR-tyrosine kinase (TK) inhibition. Two potent compounds, 1-amino-4-(4-[4-amino-2-sulfophenyl]anilino)-9,10-dioxoanthracene-2-sulfonic acid (NSC125910), and nogalamycin N-oxide (NSC116555) were identified with IC50 values against EGFR-TK comparable to gefitinib; 16.14 and 37.71 nM, respectively. However, only NSC116555 demonstrated cytotoxic effects against non-small-cell lung cancer, A549, shown in the cell cytotoxicity assay with an IC50 of 0.19 + 0.01 µM, which was more potent than gefitinib. Furthermore, NSC116555 showed cytotoxicity against A549 via apoptosis in a dose-dependent manner. |
| Databáze: | OpenAIRE |
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