Targeting Breast Cancer with Dasatinib Derivatives: A Multi-Parameter Strategy to Uncover Potent Lead Compounds

Background

Breast cancer is the most commonly diagnosed cancer and the second most prominent cause of death in women. Owing to its intricate nature involving multiple cell types, preventing its onset is challenging. Tyrosine kinase plays a crucial role in cancer development and PTK6, a non-receptor kinase, is recognized as a prognostic biomarker for cancer. Consequently, inhibition of PTK6 has emerged as a potential strategy to curb breast cancer cell proliferation and survival. Dasatinib, an oral SRC-family kinase inhibitor, exhibits robust anti-proliferative, anti-metastatic, and anti-osteoclastic properties, demonstrating sensitivity in triple-negative or basal-like breast cancer cell lines.

Materials and Methods

In this context, our study aimed to identify potent lead compounds against breast cancer by leveraging dasatinib derivatives in the pursuit of robust inhibitors. Our methodology encompassed various parameters, including derivative construction by the online tool MolOpt which is freely available and widely used. Further molecular docking, ADME analysis, PASS prediction, rodent toxicity assessment, potential adverse effect evaluation, and MD with PCA calculations were investigated.

Results

Through meticulous analysis, we compiled a substantial dataset of 163 derivatives from which the top two compounds compound 1 and compound 10 emerged following rigorous parameter evaluation.

Conclusion

After filtration, the identified candidates underwent further scrutiny via MD and PCA analyses which helped to ascertain their potential as promising drug-like substances capable of inhibiting breast cancer effectively.