Design,Synthesis, and Biological Evaluation of Novel MAO-A Inhibitors Targeting Lung Cancer

Lung cancer is one of the most common causes of cancer-related deaths worldwide. Monoamine Oxidase-A (MAO-A) enzyme mediates the production of reactive oxygen species (ROS) that trigger DNA damage and oxidative injury of cells resulting in tumor initiation and progression. Available MAO-A inhibitors are used as antidepressants, however, their role as anticancer agents is still under investigation. Ligand- and structure-based drug design approaches guided the discovery and development of novel MAO-A inhibitors. A series of 1H indole-2-carboxamide derivatives was prepared and characterized using 1H-NMR, 13C-NMR, and IR. The antiproliferative effects of MAO-A inhibitors were evaluated using the cell viability assay (MTT), and MAO-A activity was evaluated using MAO-A activity assay. The presumed inhibitors significantly inhibited the growth of lung cell lines in a dose- and time dependent manner. The half maximal inhibitory concentration (IC₅₀) values of MAO-A inhibitors (S1, S2, S4, S7, and S10) were 33.37, 146.1, 208.99, 307.7, and 147.2 µM, respectively, in A549. Glide docking against MAO-A showed that the derivatives accommodate MAO-A binding cleft and engage with key binding residues. MAO-A inhibitors provide significant and consistent evidence on MAO-A activity in lung cancer and present a potential target for the development of new chemotherapeutic agents.     

Model Independent QED Corrections to the Process ep → eX

We give an exhaustive presentation of the semi-analytical approach to the model independent leptonic QED corrections to deep inelastic neutral current lepton-nucleon scattering. These corrections include photonic bremsstrahlung from and vertex corrections to the lepton current of the order φ(α) with soft photon exponentiation. A common treatment of these radiative corrections in several variables — leptonic, hadronic, mixed, Jaquet-Blondel variables — has been developed and double differential cross sections are calculated. In all sets of variables we use some structure functions, which depend on the hadronic variables and which do not have to be defined in the quark parton model. The remaining numerical integrations are twofold (for leptonic variables) or onefold (for all other variables). For the case of hadronic variables, all phase space integrals have been performed analytically. Numerical results are presented for a large kinematical range, covering fixed target as well as collider experiments at HERA or LEP⊗LHC, with a special emphasis on HERA physics.