In Silico Design and Evaluation of Novel Benzoxazine Derivatives as Potential Cdk9 Inhibitors for Anticancer Therapy

Cyclin-Dependent Kinase 9 (CDK9) is a crucial regulator of tumour cell proliferation, survival, and oncogenic gene expression. Transcriptional dysregulation is a known hallmark of cancer. In this work, a novel series of compounds containing benzoxazine was designed and evaluated in silico as possible therapeutic drugs that target CDK9. To evaluate the binding affinities and interaction patterns of ten proposed compounds (1–10) with the CDK9 enzyme (PDB ID: 6GHZ), molecular docking studies were conducted using AutoDock and AutoDock Vina. With binding affinities of −9.0 kcal/mol and −8.8 kcal/mol, respectively, Compound 6 and Compound 4 outperformed the standard medication CDK9-IN-23 (−8.2 kcal/mol) among the series. Additionally, a physicochemical study and in silico ADMET showed that most of these substances adhere to Lipinski's rule of five, having acceptable pharmacokinetic characteristics and no anticipated AMES toxicity. These results demonstrate the benzoxazine scaffold's potential as a viable lead for targeted anticancer treatment.