Novel conjugates of zerumbone with quinazolin-4(3H)-ones and quinolines as potent anticancer inhibitors: Synthesis, biological evaluation and docking studies

• Published in: Results in Chemistry 2024-01, Vol.7, p.101427, Article 101427
• Main Authors: Hung Truong, Ngoc, Anh Le, Duc, Ha Vu, Thi, Inh Cam, Thi, Nghi Do, Huu, Cuong Nguyen, Manh, Vu Tran, Khac, Nguyen Tran, Hanh, Chung Pham, Van, Chinh Luu, Van
• Format: Article
• Language: English
• Subjects: Anti-inflammatory; Cytotoxicity; Zerumbone
• ISSN: 2211-7156; 2211-7156
• DOI: 10.1016/j.rechem.2024.101427

[Display omitted] •11 new zerumbone conjugates with quinazolinone-4(3H)-ones and quinolines were prepared.•The conjugates were structurally determined by NMR and HRMS spectroscopies.•Anti-inflammatory and cytotoxic activities of these conjugates were screened.•Docking and molecular dynamics simulation were performed using protein EGFR (4HJO) The alkylation reaction was used to couple zerumbone with the 3-substituted quinazolinone-4(3H)-ones and quinolines, resulting in the formation of 11 new conjugates. Their structures were fully characterized by 1D-, 2D-NMR, and HRMS spectral data. The evaluation of their anti-inflammatory activity was examined by inhibiting NO production in RAW 267.4 cells. Screening for their cytotoxic activity was performed using three human cancer cell lines HepG2, SK-LU-1, and MCF-7. The results indicated that all 11 novel conjugates exhibited potent cytotoxic activity against the tested cell lines with IC50 values in the range of 1.01–9.86 µg/mL, which were stronger than those of the parent compound zerumbone. In silico EGFR inhibitory activity was also performed by docking and molecular dynamics simulation studies to find out the most potent compounds based on the main interactions of zerumbone derivatives 16a-k with important amino acids of EGFR (PDB ID 4HJO) protein in its active site.