Synthesis, molecular docking and dynamics studies of pyridazino[4,5-b]quinoxalin-1(2H)-ones as targeting main protease of COVID-19.

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created a crisis in public health. Because, the 3CLpro, the main protease of SARS-CoV-2, possesses a critical role in coronavirus replication, many efforts have been devoted to developing various inhibitors to prevent the fast spread of COVID-19. In the current work, a number of various pyridazino[4,5-b]quinoxalin-1(2H)-one derivatives bearing thiadiazine and thiadiazole fragments has been prepared via a straightforward and practical strategy involving the reaction of 2-(ethoxycarbonyl)-3-formylquinoxaline 1,4-dioxide with thiocarbohydrazide under reflux conditions. To determine the bioavailability of pyridazino[4,5-b]quinoxalin-1(2H)-one derivatives, Lipinski's rule of five has been carried out. Regarding this rule, none of the synthesized compounds exhibit any deviation from Lipinski's rule of five. Furthermore, molecular docking and molecular dynamics approaches have been implemented to figure out the potential interactions of products with SARS-CoV-2 main protease. The outcomes of molecular docking studies demonstrate that the phenyl and nitrophenyl substituted pyridazino[4,5-b]quinoxalin-1(2H)-one show the lowest binding affinity among the other compounds, indicating a favorable orientation in the active site of the chymotrypsin-like cysteine protease. In addition, the MD simulation performed to evaluate the stability of the protein-ligand complex represents that the average binding energy of the nitrophenyl complex is less than that of the phenyl complex. Therefore, according to the in silico results, the inhibitory effect of the nitrophenyl complex is more significant than the phenyl complex.Communicated by Ramaswamy H. Sarma.

Pyrido[1,2-e]purine: Design and Synthesis of Appropriate Inhibitory Candidates against the Main Protease of COVID-19.

A series of tricyclic and polycyclic pyrido[1,2-e]purine derivatives were designed and synthesized via a two-step, one-pot reaction of 2,4-dichloro-5-amino-6-methylpyrimidine with pyridine under reflux conditions. Various derivatives of pyrido[1,2-e]purine were also synthesized by substituting the chlorine atom with secondary amines. After careful physiochemical and pharmacokinetic predictions, the inhibitory effects of the synthesized compounds against the main protease of SARS-CoV-2 have been evaluated by molecular docking and molecular dynamics approaches. The in silico results revealed that among all of the studied compounds, the morpholine/piperidine-substituted pyrido[1,2-e]purine derivatives are the best candidates as effective inhibitors of SARS-CoV-2.

AI and Ethics: Ethical and Educational Perspectives for LIS

The growth of artificial intelligence (AI) technologies has affected higher education in a dramatic way, shifting the norms of teaching and learning. With these shifts come major ethical questions relating to surveillance, exacerbated social inequality, and threats to job security. This article overviews some of the discourses that are developing on the integration of AI into the higher education setting, with focus on LIS and librarianship, considers the role of LIS and librarianship in intervening in the trajectory of AI in learning and teaching, and weighs in on the place of professional LIS ethics in relation to confronting AI-led technological transformations.