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Synthesis of new Spiropyrazole derivatives under microwaves irradiation and docking study for inhibition the microbes and COVID-19.

ABSTRACT: Synthesis of a new series of spiropyrazole derivatives using microwaves irradiation with high yield in minutes was achieved through a cycloaddition reaction of nitrile imines and arylidenes of 5-bromo-indan-1-one. The structure of the new spiropyrazoles was assured based on their available spectral analyses and the comparison of the extracted data with the literature reports. Molecular docking simulations of all new synthesized spiropyrazole derivatives into leucyl-tRNA synthetase editing domain of Candida albicans (Pdb: 2WFC) indicated that about seven spiropyrazole derivatives can fit deeply in the active site via the formation of stable complexes. In addition, the docking study was utilized to tested the ability of these spiropyrazoles to inhibit COVID-19 through the interaction with COVID-19 main protease (Pdb: 6LU7). The results were surprising which revealed high docking score ranging from -7.764 to -5.9464 kcal/mol. Moreover, the nitrogen atom of pyrazole, Br atom and the C=O group of indanone are essential parts in the binding mode of almost the active derivatives. The results of the docking study are a glimmer of hope to complete the study on these compounds and examine them in the laboratory to ensure their effectiveness as antimicrobials and antiviral, especially Covid-19. Moreover, pharmacokinetics and physicochemical properties were studied.

SUBMITTER: Masaret GS

PROVIDER: S-EPMC9232256 | biostudies-literature |

REPOSITORIES: biostudies-literature

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