Exploring imidazo[1,2-a]pyridine hybrids in cancer therapy: ADMET profiling, molecular docking, MD simulations and DFT calculations

探索咪唑并[1,2-a]吡啶杂合物在癌症治疗中的应用:ADMET分析、分子对接、MD模拟和DFT计算

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Abstract

Cyclin dependent kinase 2 (CDK2) is a critical regulator of cell cycle progression and an important therapeutic target in cancer treatment. In this study, imidazo[1,2-a]pyridine-quinazoline hybrids were computationally explored as potential CDK2 inhibitors using an integrated in silico framework. Virtual screening enabled the prioritization of compounds exhibiting favourable interactions with the CDK2 active site particularly through hinge region residues. Among the screened library, two compounds AD20 and AD28 emerged as top ranked based on a consensus assessment of binding affinity and predicted pharmacokinetic suitability. These compounds demonstrated stable binding behaviour, favourable drug likeness, and electronic features supportive of molecular stability and reactivity. Importantly, the findings represent computational prioritization rather than experimental validation. Overall, this study highlights imidazo[1,2-a]pyridine hybrids as promising scaffolds for further optimization and provides a rational basis for future experimental evaluation toward CDK2 targeted anticancer drug development.

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