Synthesis, crystal structure, DFT, molecular docking and antitumor activity of 4-(2-chlorobenzyl)-1-(5-fluoro-2-hydroxy-3-((4-methylpiperidin-1-yl)methyl)phenyl)-[1,2,4]triazolo[4,3-a]quinazolin-5(4H)-one
In this study, the compound 4-(2-chlorobenzyl)-1-(5-fluoro-2-hydroxy-3-((4-methylpiperidin -1-yl)methyl)phenyl)-[1,2,4]triazolo[4,3- a ]quinazolin-5(4 H )-one ( 1 ) was synthesized for the first time, and its structure was characterized by 1 H NMR, 13 C NMR, MS and FT-IR spectra. Single crystals of...
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Published in | Research on chemical intermediates Vol. 47; no. 9; pp. 3609 - 3627 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Dordrecht
Springer Netherlands
01.09.2021
Springer Nature Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | In this study, the compound 4-(2-chlorobenzyl)-1-(5-fluoro-2-hydroxy-3-((4-methylpiperidin -1-yl)methyl)phenyl)-[1,2,4]triazolo[4,3-
a
]quinazolin-5(4
H
)-one (
1
) was synthesized for the first time, and its structure was characterized by
1
H NMR,
13
C NMR, MS and FT-IR spectra. Single crystals of compound
1
were grown in acetonitrile and the structure was confirmed by X-ray diffraction. The DFT-optimized structure was consistent with that determined by X-ray diffraction. Geometrical parameter, molecular electrostatic potential and frontier molecular orbital analyses were performed using the DFT/B3LYP/6-311G (2d, p) method. The vibrational assignment was based on the characteristic vibrational absorption band of compound
1
. The theoretical and experimental
13
C NMR chemical shifts exhibited good correlation. Molecular docking suggests favorable interactions between compound
1
and SHP2 protein. The SHP2 enzyme inhibition rate of compound
1
was 12.40% at 10 μM. The antitumor activity of
1
was better than that of the reference compound in human hepatoma cells SMMC7721 (IC
50
= 757 µM) and human melanoma cells A375 (IC
50
= 70.19 µM).
Graphic abstract |
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ISSN: | 0922-6168 1568-5675 |
DOI: | 10.1007/s11164-021-04491-x |