A reliable QSAR model of crystal-based pyridine derivatives to design and determine ADMET properties, molecular docking, and molecular dynamics of a novel complex for cervical cancer therapy

In this study, the Quantitative Structure-Activity Relationship (QSAR) method has been employed to investigate ۳۰ crystal structures of pyridine and bipyridine derivatives. The half-maximal inhibitory concentration (IC۵۰) related to the HeLa cell line of compounds was modeled utilizing a Multiple Linear Regression (MLR) method. According to the statistical results, the coefficient of determination (R۲) was equal to ۰.۸۰۸ and ۰.۹۰۸ for the training and test sets, respectively. Furthermore, evaluation techniques for MLR, including Q۲LOO=۰.۷۸۴, Q۲LMO=۰.۸۰۷, Y-randomization=۰.۱۱۹, and Q۲cv=۰.۷۶۳, were employed to determine the accuracy of the introduced model. Following the procedures mentioned above, a novel anticancer structure was designed, for which molecular docking was also performed with Epidermal Growth Factor Protein (PDBID: ۱M۱۷). In silico ADME (absorption, distribution, metabolism, and excretion) calculation for the designed compound was also carried out, and the results revealed that the proposed structure could be used as an appropriate drug candidate. In addition, the toxicity of the designed compound was estimated using prediction of the activity and structure spectra (PASS) software. Molecular Dynamics (MD) simulation was processed by evaluating ligand-binding stability using root-mean-square deviation (RMSD) with NAMD software and CHARMM۲۷ force field. The designed compound has a remarkable potential to be considered a suitable inhibitor.

کلیدواژه ها:

QSAR model ، Molecular docking and MD Simulations ، ADME and PASS prediction ، Pyridine and Bipyridine derivatives ، cervical cancer therapy