Abdulwahab, Muhammad Kumayl and Sidek, Fatin Nur Elyana Mohd and Daker, Maelinda and Marzuki, Marini and Keflee, Rashidi Dzul and Tan, Yee Seng and Adzrill, Muhammad Hakim Muhamad and Norazit, Anwar and Noor, Suzita Mohd and Halim, Siti Nadiah Abdul and Goh, Bey Hing and Ariffin, Azhar (2025) Anticancer activity of fused quinazoline-quinazolinone: Synthesis, biological evaluations, and computational studies. Journal of Molecular Structure, 1326. p. 141065. ISSN 0022-2860, DOI https://doi.org/10.1016/j.molstruc.2024.141065.
Full text not available from this repository.Abstract
Although several methods for the synthesis of the fused quinazoline-quinazolinone derivatives have been reported, their biological activity has not been thoroughly investigated. The objectives of the present study were to synthesize a series of fused quinazoline-quinazolinone derivatives and evaluate them for their anticancer activity alongside their potential as EGFR inhibitors, through in vitro, in vivo and in silico studies. This study presents the synthesis, biological evaluation, and computational analysis of a series of quinazoline-quinazolinone fused ring derivatives as potential epidermal growth factor receptor (EGFR) inhibitor targeting non-small cell lung cancer (NSCLC). Compounds 3a-e were synthesized through the cyclization of quinazolinone with respective aldehydes, yielding new quinazoline ring. Compound 3b recorded significant activity against H1975 cells (IC50 = 15.9 f 1.2 mu M) and moderate activity against A549 cells (IC50 = 32.9 f 1.2 mu M) in the MTT assay, compared to gefitinib (IC50 = 20.2 f 1.1 mu M and 34.0 f 1.2 mu M, respectively). It also inhibited EGFR and PI3K enzymes at 10 mu M in the Western Blot assay. The compound induced apoptosis and cell cycle arrest at the G0/G1 phase in H1975 cells. Additionally, the fish embryo acute toxicity assay showed that the compound was non-toxic at 400 mu M on zebrafish embryos. In silico studies using molecular docking and molecular dynamics revealed that the binding of the compound to EGFR was stabilized by hydrophobic and hydrogen bonding interactions. These results suggest that the quinazoline-quinazolinone derivative holds promise as an EGFR inhibitor and warrants further investigation.
| Item Type: | Article |
|---|---|
| Funders: | Ministry of Higher Education Malaysia via Fundamental Research Grant Scheme (FRGS/1/2022/STG04/UM/02/1), Ministry of Health, Malaysia (NMRR-18-231-40326), Universiti Malaya via Universiti Malaya Impact Oriented Interdisciplinary Research Grant (IIRG001C-2022FNW) |
| Uncontrolled Keywords: | Quinazoline-quinazolinone derivative; EGFR inhibitor; H1975; Apoptosis; Fish embryo acute toxicity test |
| Subjects: | Q Science > QD Chemistry R Medicine > R Medicine (General) |
| Divisions: | Faculty of Medicine > Biomedical Science Department Faculty of Medicine > Department of Molecular Medicine Faculty of Science > Department of Chemistry |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 12 Mar 2025 01:11 |
| Last Modified: | 12 Mar 2025 01:11 |
| URI: | http://eprints.um.edu.my/id/eprint/47793 |
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