Designing of Novel Quinolines Derivatives as Hepatocellular Carcinoma Inhibitors by Using In silico Approaches
Biointerface Research in Applied Chemistry · 2022
Cancer is one of the very common diseases requiring long-term treatment, tubulin plays an important role in the development of cancer, and the use of colchicine binding site inhibitors against Hepatocellular Carcinoma has become the most common approach. A series of thirty quinoline derivatives have recently been identified as promising tubulin inhibitors with potent activity against human Hepatocellular Carcinoma. To design anti-cancer drugs, we applied the 3D-QSAR approach, this method is based on two contours (CoMFA and CoMSIA), the results obtained in two these contours are (R2 = 0.98, Q2 = 0.68, r2ext = 0.96) and (R2= 0.98, Q2 = 0.57, r2ext = 0. 97), respectively, this indicates that the model is trustworthy. The results indicate that the hydrophobic field contributes more (58% ); based on these results, three quinoline derivatives (Z1, Z2, and Z3) are proposed as potent colchicine binding site inhibitors against hepatocellular carcinoma activities. Furthermore, molecular docking was utilized to compare the stability of complexes (ligand-receptor) based on the type of binding and the total score. The ADME has been utilized to evaluate the pharmacokinetic characteristics of the designed drugs; we can conclude that by using the results, all designed compounds are the best, and based on the results found at Docking and ADMET, and to identify the stability of newly compounds, molecular dynamic simulation was used for compounds Z2-3, the results found show that these molecules have better stability, which means that they have greater activity against hepatocellular carcinoma.