Trifluoromethyl quinoline derivative targets inhibiting HDAC1 for promoting the acetylation of histone in cervical cancer cells

• DOI: 10.1016/j.ejps.2024.106706
• Publication Date: 2024-01-19T03:54:55Z
• Authors: Ting Zhang; Changhua Zhou; Mengfan Lv; Jia Yu; Sha Cheng; Xudong Cui; Xinwei Wan; Mashaal Ahmad; Bixue Xu; Juan Qin; Xueling Meng; Heng Luo
• Keywords: HDAC1; HeLa

Cervical cancer is the leading cause of death among gynecological malignant tumors, especially due to poor prognosis patients with advanced tumors recurrence, metastasis, and chemotherapy resistance. Therefore, exploring new antineoplastic drugs high efficacy low toxicity may bring expectations in cervical cancer. Natural products their derivatives exert an antitumor activity. this work, combined network pharmacology analysis experimental validation, we investigated anti-cervical activity molecular mechanism a trifluoromethyl quinoline (FKL) derivative vivo vitro. FKL117 inhibited proliferation cells dose time-dependent manner, induced apoptosis HeLa cells, arrested cell cycle G2/M phase, regulated expression apoptotic cycle-related proteins Bcl-2, Bax, cyclin B1, CDC2. We used online databases obtain HDAC1 as one possible targets target binding affinity were modeled by docking. The results showed that formed hydrogen bond had good ability. found targeted inhibit function increased acetylation histone H3 H4, which was also confirmed vivo. migration HMGB1 from nucleus cytoplasm further verified above results. In conclusion, our study suggested might be novel candidate for targeting inhibition against