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

• Published in: Scientific reports 2024-04, Vol.14 (1), p.9223-9223, Article 9223
• Main Authors: Gao, En, Wang, Ya, Fan, Gao-lu, Xu, Guiqing, Wu, Zi-Yuan, Liu, Zi-Jun, Liu, Jian-Cheng, Mao, Long-Fei, Hou, Xixi, Li, Shouhu
• Format: Article
• Language: English
• Subjects: 1,2,3-triazole; 631/154; 631/337; 631/45; 631/92; Acute toxicity; Adenocarcinoma; Anticancer drug; Antifungal agents; Antitumor activity; Apoptosis; Cell apoptosis; Cell migration; Colonies; Gefitinib; Humanities and Social Sciences; Inhibitor drugs; Lung cancer; multidisciplinary; Non-small cell lung carcinoma; Science; Science (multidisciplinary); Small cell lung carcinoma; Targeted cancer therapy; Toxicity; Triazoles; Tumor cell lines
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-60000-1

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 IC 50 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 IC 50 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.