Design, synthesis, biological evaluation and computational study of novel triazolo [4,3-a]pyrazin analogues
| Autor: | Sanjay K. Rathwa, Divya J. Jethava, Manoj N. Bhoi, Hitesh D. Patel, Mahesh S. Vasava, Prachi T. Acharya, Zeel A. Bhavsar, Dhanji P. Rajani |
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| Rok vydání: | 2019 |
| Předmět: |
chemistry.chemical_classification
biology 010405 organic chemistry Chemistry Organic Chemistry Active site Plasmodium falciparum Carbon-13 NMR 010402 general chemistry biology.organism_classification 01 natural sciences Combinatorial chemistry 0104 chemical sciences Analytical Chemistry Inorganic Chemistry Enzyme Docking (molecular) Zymogen biology.protein Proton NMR Molecule Spectroscopy |
| Zdroj: | Journal of Molecular Structure. 1184:168-192 |
| ISSN: | 0022-2860 |
| DOI: | 10.1016/j.molstruc.2019.01.091 |
| Popis: | The triazolo [4,3-a]pyrazin analogues are of interest due to their potential activity against various infectious and non-infectious disease. In search of suitable potent drug candidate, we report here the design, synthesis, characterization, biological activities and computation study of novel triazolo [4,3-a]pyrazin analogues. The synthesized molecules were characterized by various spectroscopic studies such as IR, Mass, 1H NMR, 13C NMR and elemental analysis. The newly synthesized compounds were evaluated for their in vitro biological activities such as anti-malarial, anti-tuberculosis, anti-bacterial and anti-fungal activities against plasmodium falciparum, H37Rv, various bacterial and fungal strains, respectively. The molecular docking study was carried out with enzyme aspartic proteinase zymogen proplasmepsin II from plasmodium falciparum to analyze their binding orientation in the active site of the aspartic proteinase enzyme. The best docking complex was subjected to molecular dynamics simulation to illustrate the stability of these complexes and the most prominent interactions during the simulated trajectory. We have also calculated ADMET properties of all the synthesized compounds to predict the pharmacokinetic properties for the selection of the active and bioavailability of compounds. |
| Databáze: | OpenAIRE |
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