2. Academic Validation
  3. Discovery of gefitinib-1,2,3-triazole derivatives against lung cancer via inducing apoptosis and inhibiting the colony formation

Discovery of gefitinib-1,2,3-triazole derivatives against lung cancer via inducing apoptosis and inhibiting the colony formation

  • Sci Rep. 2024 Apr 22;14(1):9223. doi: 10.1038/s41598-024-60000-1.
En Gao 1 2,  Ya Wang 3,  Gao-Lu Fan 4,  Guiqing Xu 3,  Zi-Yuan Wu 5,  Zi-Jun Liu 5,  Jian-Cheng Liu 5,  Long-Fei Mao 6,  Xixi Hou 7,  Shouhu Li 8
Affiliations

Affiliations

  • 1 School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, 453000, China. ge_163@126.com.
  • 2 State Key Laboratory of Quality Research in Chinese Medicine/Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau, China. ge_163@126.com.
  • 3 School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, 453000, China.
  • 4 Department of Pharmacy, Luoyang Third People' Hospital, Luoyang, 471000, China.
  • 5 College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, 263 Kaiyuan Road, Luoyang, 471003, China.
  • 6 College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, 263 Kaiyuan Road, Luoyang, 471003, China. longfeimao1988@163.com.
  • 7 Department of Pharmacy, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China.
  • 8 School of Pharmacy, Xinxiang University, Xinxiang, 453000, Henan, China.
PMID: 38649732 DOI: 10.1038/s41598-024-60000-1
Abstract

A series of 20 novel gefitinib derivatives incorporating the 1,2,3-triazole moiety were designed and synthesized. The synthesized compounds were evaluated for their potential Anticancer activity against EGFR wild-type human non-small cell lung Cancer cells (NCI-H1299, A549) and human lung adenocarcinoma cells (NCI-H1437) as non-small cell lung Cancer. In comparison to gefitinib, Initial biological assessments revealed that several compounds exhibited potent anti-proliferative activity against these Cancer cell lines. Notably, compounds 7a and 7j demonstrated the most pronounced effects, with an IC50 value of 3.94 ± 0.17 µmol L-1 (NCI-H1299), 3.16 ± 0.11 µmol L-1 (A549), and 1.83 ± 0.13 µmol L-1 (NCI-H1437) for 7a, and an IC50 value of 3.84 ± 0.22 µmol L-1 (NCI-H1299), 3.86 ± 0.38 µmol L-1 (A549), and 1.69 ± 0.25 µmol L-1 (NCI-H1437) for 7j. These two compounds could inhibit the colony formation and migration ability of H1299 cells, and induce Apoptosis in H1299 cells. Acute toxicity experiments on mice demonstrated that compound 7a exhibited low toxicity in mice. Based on these results, it is proposed that 7a and 7j could potentially be developed as novel drugs for the treatment of lung Cancer.

Keywords

1,2,3-triazole; Anticancer drug; Cell apoptosis; Cell migration; Gefitinib.

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