In-silico activity prediction and docking studies of some flavonol derivatives as anti-prostate cancer agents based on Monte Carlo optimization

Abstract

The QSAR models are employed to predict the anti-proliferative activity of 81 derivatives of flavonol against prostate cancer using the Monte Carlo algorithm based on the index of ideality of correlation (IIC) criterion. CORAL software is employed to design the QSAR models. The molecular structures of flavonols are demonstrated using the simplified molecular input line entry system (SMILES) notation. The models are developed with the hybrid optimal descriptors i.e. using both SMILES and hydrogen-suppressed molecular graph (HSG). The QSAR model developed for split 3 is selected as a prominent model ($${R}_{Validation}^{2}$$ R Validation 2 = 0.727, $${IIC}_{validation}$$ IIC validation = 0.628, $${Q}_{Validation}^{2}$$ Q Validation 2 = 0.642, and $${\overline{r} }_{m}^{2}$$ r ¯ m 2 =0.615). The model is interpreted mechanistically by identifying the characteristics responsible for the promoter of the increase or decrease. The structural attributes as promoters of increase of pIC50 were aliphatic carbon atom connected to double-bound (C…=…, aliphatic oxygen atom connected to aliphatic carbon (O…C…), branching on aromatic ring (c…(…), and aliphatic nitrogen (N…). The pIC50 of eight natural flavonols with pIC50 more than 4.0, were predicted by the best model. The molecular docking is also performed for natural flavonols on the PC-3 cell line using the protein (PDB: 3RUK).

In Silico and In Vivo Evaluation of the Maqui Berry (Aristotelia chilensis (Mol.) Stuntz) on Biochemical Parameters and Oxidative Stress Markers in a Metabolic Syndrome Model

“…Several mechanisms have been proposed to explain the multiple bioactivities of MB components. The use of molecular docking + molecular dynamics simulation has been proven useful for the prediction or delimitation of the potential molecular mechanism of action of some molecules, particularly those of natural origin and in potential multitarget ligands [34][35][36][37][38][39][40][41].…”

The System of Self-Consistent Models: The Case of Henry’s Law Constants

“…Finally, last but not least, the proposed approach is implemented through one program available on the internet (http://www.insilico.eu/coral, accessed on 12 October 2023), and that has been used as a tool to develop QSPR/QSAR models many times [17][18][19][20][21][22][23][24].…”