3D-QSAR and Docking Studies of a Series ofβ-Carboline Derivatives as Antitumor Agents of PLK1

Abstract

An alignment-free, three dimensional quantitative structure-activity relationship (3D-QSAR) analysis has been performed on a series ofβ-carboline derivatives as potent antitumor agents toward HepG2 human tumor cell lines. A highly descriptive and predictive 3D-QSAR model was obtained through the calculation of alignment-independent descriptors (GRIND descriptors) using ALMOND software. For a training set of 30 compounds, PLS analyses result in a three-component model which displays a squared correlation coefficient (r2) of 0.957 and a standard deviation of the error of calculation (SDEC) of 0.116. Validation of this model was performed using leave-one-out,q2looof 0.85, and leave-multiple-out. This model gives a remarkably highr2pred(0.66) for a test set of 10 compounds. Docking studies were performed to investigate the mode of interaction betweenβ-carboline derivatives and the active site of the most probable anticancer receptor, polo-like kinase protein.

Alignment independent 3D-QSAR, quantum calculations and molecular docking of Mer specific tyrosine kinase inhibitors as anticancer drugs

“…DRY, O, N1, and TIP probes were used to compute PLS coefficients for the models (Ghasemi and Davoudian, 2014). The FFD variable selection method chose a set of 370 descriptors from a pool of 680.…”

Steroidal 5α-Reductase Inhibitors: A Comparative 3D-QSAR Study Review

“…3D-QSAR techniques are particularly effective in correlating the 3D structures of the molecules and their bioactivities based on statistical techniques. A validated 3D-QSAR model not only helps in better understanding of the structure–activity relationships of any class of molecules but also provides the researcher an insight at the molecular level about the lead molecules for further developments. − Thus, information obtained from 3D-QSAR analysis provides important guidelines for the drug design process.…”

New β-carboline derivatives containing imidazolium as potential VEGFR2 inhibitors: synthesis, X-ray structure, antiproliferative evaluations, and molecular modeling

“…[14][15][16] In recent decades, there have been intense research efforts in the design and development of β-carbolines as a new class of antitumor agents, and a large number of β-carboline derivatives have been prepared in search of agents that are more potent. The results indicate that this class of compounds exert antitumor effects through various mechanisms of action, including intercalating with DNA, 17,18 and by inhibition of cyclin-dependent kinase (CDK), 19 topoisomerases I and II, 20 polo-like kinase 1 (PLK1), 21,22 and IκB kinase. 23 Imidazo [1,5-a]pyridines are another important class of heterocyclic compounds because of their unique biological activities.…”