Design of potential anti-melanoma agents against SK-MEL-5 cell line using QSAR modeling and molecular docking methods

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 quantitative structure-activity relationship (QSAR) model and molecular docking simulation able to predict the cytotoxic effect of diverse chemical 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 pGI 50 was recorded. The QSAR model was built using fifty (50) compounds and the best-generated model based on multiple linear regression showed, respectively good quality of fits [ R 2 (0.864), R 2 adjusted (0.846), Q 2 cv (0.841) and R 2 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 pGI 50 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.

3D-QSAR Studies of 1,2,4-Oxadiazole Derivatives as Sortase A Inhibitors

“…The range of the R 2 and Q 2 values were 0.34 to 0.57 and -0.45 to -0.65, respectively. It needs to be mentioned that every Y vector random stage was followed by the perfect training method to improve the new QSAR model, involving the choice of the most proper descriptors [ 68 ].…”

“…The range of the R 2 and Q 2 values were 0.34 to 0.57 and -0.45 to -0.65, respectively. It needs to be mentioned that every Y vector random stage was followed by the perfect training method to improve the new QSAR model, involving the choice of the most proper descriptors [68]. Also, the hydrogen of the hydroxyl group p-hydroxyphenyl, present on the other side of the oxadiazole near the desirable region, is available for two compounds-categorized as active and the least active.…”

The Inhibitory Potency of Major Teucrium polium Active Ingredients for the Main Protease (Mpro) of COVID-19

“…An antagonistic reaction to protein or enzyme inhibitors in vivo has been proven to be inconclusive in terms of the inhibitor's suitability as a potential medication [25]. As a result, in regiment development, the pharmacokinetic studies of the inhibitor ADME including drug-likeness assessments are critical in determining the inhibitor is available to a biological system [25,26]. Furthermore, the poor pharmacokinetic features of potential inhibitors with very toxic properties on cells are the primary cause for the discontinuation of clinical trials [27].…”

Antimalarial activity of curcumin and kaempferol using structure-based drug design method

“…Furthermore, molecular docking involves selecting the three-dimensional active binding site of the receptor molecule and calculating the binding affinity and energy of the resulting orientation [15]. The bond affinity value was determined by the highest bond affinity or the lowest bond energy (more negative values) indicating the most favorable conformation [16].…”