This study describes the synthesis of novel 1,3,5-triazine derivatives as potent inhibitors of cervical cancer. The compounds were initially tested for inhibition of PI3K/mTOR, where they showed significant inhibitory activity. The top-ranking molecule (compound 6 h) was further tested against class I PI3K isoforms, such as PI3Kα, PI3Kβ, PI3Kγ and PI3Kδ, where it showed the most significant activity against PI3Kα. Compound 6 h was then tested for anti-cancer activity against triple-negative breast cancer cells (MDA-MB321), human breast cancer cells (MCF-7), human cervical cancer cells (HeLa) and human liver cancer cells (HepG2), and it showed the greatest potency against HeLa cells. The effects of compound 6 h were further evaluated against the HeLa cells, where it showed significant attenuation of cell viability by inducing cell cycle arrest in the G1 phase. Compound 6 h induced apoptosis and reduced migration and invasion of HeLa cells. Western blotting analysis showed that 6 h inhibited PI3K and mTOR with positive modulation of Bcl-2 and Bax levels in HeLa cells. The effects of compound 6 h were also investigated in a tumour xenograft mouse model, where it showed reduction of tumour volume and weight. It also inhibited the PI3K/Akt/mTOR signalling cascade in xenograft tumour tissues, as evidenced by western blotting analysis. The results of the present study suggest the possible utility of the designed 1,3,5-triazine derivative as a potent inhibitor of cervical cancer.

本研究描述了作为宫颈癌有效抑制剂的新型 1,3,5-三嗪衍生物的合成。最初测试这些化合物对 PI3K/mTOR 的抑制作用，显示出显着的抑制活性。针对 I 类 PI3K 同种型，例如 PI3Kα、PI3Kβ、PI3Kγ 和 PI3Kδ，对排名靠前的分子（化合物6h）进行了进一步测试，其中它对 PI3Kα 显示出最显着的活性。然后测试化合物6 h对三阴性乳腺癌细胞 (MDA-MB321)、人乳腺癌细胞 (MCF-7)、人宫颈癌细胞 (HeLa) 和人肝癌细胞 (HepG2) 的抗癌活性，它对 HeLa 细胞显示出最大的效力。化合物6 h的作用进一步针对 HeLa 细胞进行了评估，通过在 G1 期诱导细胞周期停滞，它显示出细胞活力的显着减弱。化合物6 h诱导细胞凋亡并减少 HeLa 细胞的迁移和侵袭。蛋白质印迹分析表明，6 小时抑制 PI3K 和 mTOR，并正调节 HeLa 细胞中的 Bcl-2 和 Bax 水平。化合物6 h的作用还在肿瘤异种移植小鼠模型中进行了研究，其中显示肿瘤体积和重量减少。蛋白质印迹分析证明，它还抑制异种移植肿瘤组织中的 PI3K/Akt/mTOR 信号级联反应。本研究的结果表明，设计的 1,3,5-三嗪衍生物可能用作宫颈癌的有效抑制剂。