Computational Investigation of the Inhibition of Chk1 and Wee1 Proteins by Chemical Constituents of Amaranthus Gangeticus

Objective: This study aimed to explore an alternative compound capable of inhibiting CHK1 (Checkpoint Kinase 1) and WEEl proteins in breast cancer using natural compounds derived from red spinach (Amaranthus gangeticus). Methods: The experiment used SMILES and 3D structure of red spinach, PASS Online for biology activity, Lipinski's rule of five for physicochemical properties predictions, as well as validation, and molecular docking of active compounds. Results: The results showed that CHK1 and WEE1 docking validation had RMSD values of 1.5 Å and 0.634 Å, respectively. The compounds 3,4,5-Trihydroxybenzoic acid, 3,5-Dimethoxy-4-hydroxybenzoic acid, 2,3,7,8-Tetrahydroxy-chromeno[5,4,3-cde]chromene-5,10-dione, 3-(3,4-Dihydroxycinnamoyl)quinic acid, 3-Methoxy-4-hydroxycinnamic acid, 4-Hydroxy-3,5-dimethoxycinnamic acid, 3-Phenylacrylic acid, 4′,5,7-Trihydroxyflavone, Catechin, and Quercetin exhibited favourable binding affinity values, molecular interactions, and predicted inhibitory effects against CHK1 by interacting with key residues LEU A 15, VAL A 23, and LEU A 137, and against WEE1 through interactions with GLU A 377, ILE A 305, VAL A 313, ALA A 326, and PHE A 433. While these findings highlight promising inhibitory potential, further in vitro and in vivo validation is needed to confirm the computational findings. Conclusion: This study found that the active compounds of red spinach could be used as a functional inhibitor of CHK1 and WEE1.