Abstract
BackgroundQSAR modelling was performed on thirty-five (35) newly discovered compounds of N-(2-phenoxy) ethyl imidazo[1,2-a] pyridine-3-carboxamide (IPA) to predict their biological activities against Mycobacterium tuberculosis (MTB-H37Rv strain) by using some numerical data derived from structural and chemical features (descriptors) of the compounds.ResultsAt first, the structure of the compounds was accurately drawn and optimized using the Spartan 14 software at DFT level of theory with B3LYP/6-31G** basis set in a vacuum. The diverse chemometric descriptors were computed from the optimized structures using the PaDEL descriptors software, and the division of the dataset into training and test sets was done based on Kennard-Stone’s algorithm. Five (5) models were generated from the training set using genetic function approximation, and model 1 was chosen as the best due to its robust internal and external validation metrics (R2train = 0.8563, R2adjusted = 0.8185, PRESS = 3.5724, average {overline{R}}_m^2 (LOO-train) = 0.6751, Q2cv = 0.7534, {R}_{mathrm{pred}}^2= 0.7543, R2test = 0.6993) which passed the model criteria of acceptability. 6-Bromo-N-(2-(4-bromophenoxy) ethyl)-2-ethylimidazo[1,2-a] pyridine-3-carboxamide (compound 13) was used as the structural template for the in silico design due to its high pMIC, and it is within the model’s chemical space.ConclusionBased on the information obtained from model 1, six (6) designed compounds with higher anti-tubercular activity were obtained. Furthermore, the ADME and drug-likeness prediction of the designed molecules showed good pharmacokinetic properties which indicate the application prospect of these compounds as novel MTB-H37Rv inhibitors. This research could help the medicinal chemists and pharmaceutical practitioners in future designing and development of more potent drug candidates.Graphical abstract
Highlights
quantitative structure-activity relationship (QSAR) modelling was performed on thirty-five (35) newly discovered compounds of N-(2-phenoxy) ethyl imidazo[1,2-a] pyridine-3-carboxamide (IPA) to predict their biological activities against Mycobacterium tuberculosis (MTB-H37Rv strain) by using some numerical data derived from structural and chemical features of the compounds
The ultimate goal of this study was to derive a robust QSAR model from the structures of some synthesized IPAs compounds which predicts their biological activities against Mycobacterium tuberculosis (MTBH37Rv strain), utilized the model to design new compounds with improved activity
In this research, chemometric modelling analysis has been thoroughly used on 35 IPA molecules as potential antitubercular agents
Summary
QSAR modelling was performed on thirty-five (35) newly discovered compounds of N-(2-phenoxy) ethyl imidazo[1,2-a] pyridine-3-carboxamide (IPA) to predict their biological activities against Mycobacterium tuberculosis (MTB-H37Rv strain) by using some numerical data derived from structural and chemical features (descriptors) of the compounds. In the global tuberculosis report of WHO (2019), data were reported by 202 countries and territories that account for more than 99% of the world’s population and estimated number of TB cases (World Health Organization (WHO) 2019). The ultimate goal of this study was to derive a robust QSAR model from the structures of some synthesized IPAs compounds which predicts their biological activities against Mycobacterium tuberculosis (MTBH37Rv strain), utilized the model to design new compounds with improved activity
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have