Synthesis, ADMET predictions, molecular docking studies, and in-vitro anticancer activity of some benzoxazines against A549 human lung cancer cells

Melanny Ika Sulistyowaty, Retno Widyowati, Galih Satrio Putra, Tutuk Budiati, Katsuyoshi Matsunami

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

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. Benzoxazines (1-5) were synthesized by reacting anthranilic acid and benzoyl chlorides. The structures of the compounds were determined with 1H, 13C-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. 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, IC50=36.6 μg/mL. Compound (3) more active as anticancer against Human cancer cells line compared with other benzoxazines.

Original languageEnglish
Pages (from-to)385-392
Number of pages8
JournalJournal of Basic and Clinical Physiology and Pharmacology
Volume32
Issue number4
DOIs
Publication statusPublished - 1 Jul 2021

Keywords

  • A549 cancer cell
  • ADMET prediction
  • benzoxazines
  • molecular docking
  • synthesis

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