Exploring novel furochochicine derivatives as promising JAK2 inhibitors in HeLa cells: Integrating docking, QSAR-ML, MD simulations, and experiments.

ABSTRACT: Cervical cancer, largely driven by high-risk human papillomavirus (HPV), remains a global health challenge. Janus tyrosine kinase 2 (JAK2) has emerged as a promising therapeutic target for HPV-induced malignancies. This study employed both in silico and in vitro approaches to discover novel JAK2 inhibitors from a library of 76 furochochicine (FCC) derivatives. Twenty-nine compounds were selected via virtual screening, synthesized, and tested for cytotoxicity against HeLa cells. Four FCCs showed potent cytotoxicity with selectivity indices (SI) greater than 3. These cytotoxicity data were used to construct QSAR models with machine learning; eXtreme Gradient Boosting (XGB) yielded the best performance (RMSE = 0.177, R² = 0.831, MAPE = 2.93 %) and was used to predict additional

SUBMITTER: Todsaporn D 

PROVIDER: S-EPMC12395164 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature