Esorubicin

Abstract: SK-MEL-5 is a human melanoma cell line that has been used in several researches to explore new therapies against melanoma.Based on this study we report on the development of quant. structure-activity relationship (QSAR) model and mol. docking simulation able to predict the cytotoxic effect of diverse chem. compounds on this cancer cell line.The dataset of seventy-two (72) cytotoxic compounds were downloaded from the National Cancer Institute database.It contains the data of compounds for which cytotoxicity results expressed by pGI₅₀ was recorded.The QSAR model was built using fifty (50) compounds and the best-generated model based on multiple linear regression showed, resp. good quality of fits [R² (0.864), R²_adjusted (0.846), Q²_cv (0.841) and R²_pred (0.885)].The model′s predictive ability was determined by a test set of twenty-two (22) compounds and the applicability domain was assessed through leveraged approach.Compounds 41 and 69 were selected as templates for in silico design because they had high pGI₅₀ activity and are within the model′s applicability domain.The obtained information from the model was explored to design novel compounds by introducing various substituents.Moreover, the designed compounds were docked into the active site of the protein (PDB CODE: 3OG7) which is responsible for melanoma cancer to elucidate their binding mode.Ia (- 12.4 kcal mol^-1) and IIb (- 12.3 kcal mol^-1) showed a better binding affinity for the target when compared with (vemurafenib, - 11.3 kcal mol^-1) the known inhibitor of the target (V600E-BRAF).These results may be of great help in early anticancer drug discovery.