Combining a QSAR Approach and Structural Analysis to Derive an SAR Map of Lyn Kinase Inhibition

Lyn kinase, a member of the Src family of protein tyrosine kinases, is mainly expressed by various hematopoietic cells, neural and adipose tissues. Abnormal Lyn kinase regulation causes various diseases such as cancers. Thus, Lyn represents, a potential target to develop new antitumor drugs. In the present study, using 176 molecules (123 training set molecules and 53 test set molecules) known by their inhibitory activities (IC50) against Lyn kinase, we constructed predictive models by linking their physico-chemical parameters (descriptors) to their biological activity. The models were derived using two different methods: the generalized linear model (GLM) and the artificial neural network (ANN). The ANN Model provided the best prediction precisions with a Square Correlation coefficient R2 = 0.92 and a Root of the Mean Square Error RMSE = 0.29. It was able to extrapolate to the test set successfully (R2 = 0.91 and RMSE = 0.33). In a second step, we have analyzed the used descriptors within the models as well as the structural features of the molecules in the training set. This analysis resulted in a transparent and informative SAR map that can be very useful for medicinal chemists to design new Lyn kinase inhibitors

Selective synthesis of novel quinolones-amino esters as potential antibacterial and antifungal agents : Experimental, mechanistic study, docking and molecular dynamic simulations

A new selective synthesis of novel quinoline carboxamides was developed by the N-alkylation reaction of methyl (2-oxo-1,2- dihydroquinolin-4-yl)-L-alaninate via phase transfer catalysis in a basic medium at room temperature. The compounds were obtained in excellent yields (70-90%) and characterized by H-1, (CNMR)-C-13 spectroscopy and mass spectra. In addition, theoretical studies at B3LYP/6-311G(d,p) level were carried out to explain the observed selectivity of the N-alkylation reaction of compound 2 . The biological activities of the synthesized compounds were studied using some bacterial and fungal strains. The results show that compounds 3h and 3i exhibit stronger antibacterial activity against Bacillus subtilis and Staphyloccocus aureus. Compound 3e showed high antifungal activity against Candida Albicans compared to other substituted quinoline carboxamides. Molecular docking and molecular dynamics studies were also carried out to investigate the binding affinities of some compounds with the target proteins, and the results were in good correlation with the experimental findings. (C) 2021 Elsevier B.V. All rights reserved.Peer reviewe