Synthesis, ADMET predictions, molecular docking studies, and in-vitro anticancer activity of some benzoxazines against A549 human lung cancer cells.
| Autor: | Sulistyowaty MI; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Airlangga, Surabaya, Indonesia., Widyowati R; Department of Pharmacognosy and Phytochemistry, Faculty of Pharmacy, Universitas Airlangga, Surabaya, Indonesia., Putra GS; Department of Pharmaceutical Chemistry, Stikes Rumah Sakit Anwar Medika, Sidoarjo, Indonesia., Budiati T; Faculty of Pharmacy, Widya Mandala Catholic University, Surabaya, Indonesia., Matsunami K; Department of Pharmacognosy, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. |
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| Jazyk: | angličtina |
| Zdroj: | Journal of basic and clinical physiology and pharmacology [J Basic Clin Physiol Pharmacol] 2021 Jun 25; Vol. 32 (4), pp. 385-392. Date of Electronic Publication: 2021 Jun 25. |
| DOI: | 10.1515/jbcpp-2020-0433 |
| Abstrakt: | Objectives: This study aims to synthesize a series of benzoxazines ( 1 - 5 ) to be examined as an epidermal growth factor receptor (EGFR) inhibitor by in-silico study. The overexpression of EGFR causes the growth of normal lung cells to become uncontrollable, which may lead to cancer formation. We also conducted the absorption, distribution, metabolism, excretions and toxicity (ADMET) properties evaluation and also examined in vitro anticancer assay on human lung cancer cells line, which is A549. Methods: Benzoxazines ( 1 - 5 ) were synthesized by reacting anthranilic acid and benzoyl chlorides. The structures of the compounds were determined with 1 H, 13 C-NMR, HRMS, UV and FT-IR spectrometric methods. Prediction of ADMET was using online pkCSM, and the molecular docking studies were using MVD with EGFR-TKIs as the target (PDB ID: 1M17). In vitro assay of anticancer activity was performed by MTT assay. Results: Compounds 1 - 5 were successfully synthesized in good yields (71-84%). The ADMET prediction showed that benzoxazines are able to be absorbed through GIT, metabolized by CYP 450, and not hepatotoxic. The title compounds have a greater Moldock Score than Erlotinib, and 3 has the highest activity against A549 compared with other benzoxazines, IC Conclusions: Compound ( 3 ) more active as anticancer against Human cancer cells line compared with other benzoxazines. (© 2021 Walter de Gruyter GmbH, Berlin/Boston.) |
| Databáze: | MEDLINE |
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