Allium cepa bioactive phytochemicals as potent ALK (Anaplastic lymphoma kinase) inhibitors and therapeutic agents against non-small cell lung cancer (NSCLC): A computational study

Abstract

Anaplastic lymphoma kinase (ALK) inhibitors go after and stop the ALK protein, which is very important for cancer growth, especially in ALK-positive cancers like non-small cell lung cancer (NSCLC). Lung cancer, particularly ALK-positive NSCLC prone to metastasis, is treated with ALK inhibitors targeting the cancer-driving ALK protein. This study explored the potential of onion (Allium cepa) phytochemicals as inhibitors of ALK for NSCLC treatment using computational methods. The in silico study evaluated the binding affinity of all phytochemicals of A. cepa and also predicted pharmacokinetics, ADMET parameters, drug-likeness, anti-carcinogenic properties, and acute toxicity prediction to find reliable and safe ALK inhibitor agents for the treatment of NSCLC. The findings revealed that three phytochemicals, fisetin, quercetin, and tricetin demonstrated promising results with favorable drug-likeness profiles and strong binding affinities for the ALK receptors. Specifically, their binding affinities were –7.6, –7.7, and –7.8 kcal/mol for the 4ANQ receptor; –7.6, –7.6, and –8.0 kcal/mol for the 4ANS receptor, and –7.7, –7.6, and –7.7 kcal/mol for the 6MX8 receptor, respectively. Additionally, these compounds showed hydrogen bond formation, which is crucial for drug discovery against ALK and is comparable to the known ALK inhibitors crizotinib and alectinib. These findings also suggest their potential as therapeutic agents. Further, in vitro and in vivo studies are warranted to validate these results and elucidate their mechanisms of action. This study highlights the potential of natural compounds from A. cepa for the development of novel NSCLC therapies.