Identification of bioactive compounds from Vaccinium vitis-idaea L. (Lingonberry) as inhibitors for treating KRAS-associated cancer: a computational approach.

Lung cancer is the cancer of the lung's epithelial cells typically characterized by difficulty breathing, chest pain, blood-stained coughs, headache, and weight loss. If left unmanaged, lung cancer can spread to other body parts. While several treatment methods exist for managing lung cancer, exploring natural plant sources for developing therapeutics offers great potential in complementing other treatment approaches. In this study, we evaluated the bioactive compounds in Vaccinium vitis-idaea for treating KRAS-associated lung cancer types. In this study, we concentrated on inhibiting the mutated Kirsten rat sarcoma viral oncogene homolog (KRAS) by targeting an associated protein (Phosphodiesterase 6δ) to which KRAS form complexes. We evaluated bioactive compounds from Lingonberry (Vaccinium vitis-idaea L.), adopting computational approaches such as molecular docking, molecular dynamics simulation, molecular mechanics/generalized Born surface area (MM/GBSA) calculations, and pharmacokinetics analysis. A total of 26 out of 39 bioactive compounds of Vaccinium vitis-idaea L. had a higher binding affinity to the target receptor than an approved drug, Sotorasib. Also, further analyses of all lead/top compounds in this study identified (+)-Catechin (Cianidanol), Arbutin, Resveratrol, and Sinapic acid, to be potential drug candidates that could be pursued. In sum, Arbutin, (+)-Catechin, and Sinapic acid are predicted to be the top compound of Vaccinium vitis-idaea L. because of their pharmacokinetic properties and drug-likeness attributes. Also, their stability to the target receptor makes them a potential drug candidate that could be explored for treating KRAS mutation-associated lung cancer.

Supplementary information: The online version contains supplementary material available at 10.1007/s40203-023-00165-1.