Synthesis, In Silico Prediction and In Vitro Evaluation of Antimicrobial Activity, DFT Calculation and Theoretical Investigation of Novel Xanthines and Uracil Containing Imidazolone Derivatives
Novel xanthine and imidazolone derivatives were synthesized based on oxazolone derivatives as a key intermediate. The corresponding xanthine and imidazolone derivatives were obtained via reaction of oxazolone derivative with 5,6-diaminouracils under various conditions. Xanthine compounds were obtain...
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Published in | International journal of molecular sciences Vol. 22; no. 20; p. 10979 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
MDPI AG
12.10.2021
MDPI |
Subjects | |
Online Access | Get full text |
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Summary: | Novel xanthine and imidazolone derivatives were synthesized based on oxazolone derivatives
as a key intermediate. The corresponding xanthine
and imidazolone derivatives
were obtained via reaction of oxazolone derivative
with 5,6-diaminouracils
under various conditions. Xanthine compounds
were obtained by cyclocondensation of 5,6-diaminouracils
with different oxazolones in glacial acetic acid. Moreover, 5,6-diaminouracils
were reacted with oxazolones
in presence of drops of acetic acid under fused condition yielding the imidazolone derivatives
. Furthermore, Schiff base of compounds
were obtained by condensing 5,6-diaminouracils
with 4-dimethylaminobenzaldehyde in acetic acid. The structural identity of the resulting compounds was resolved by IR,
H-,
C-NMR and Mass spectral analyses. The novel synthesized compounds were screened for their antifungal and antibacterial activities. Compounds
,
,
and
displayed the highest activity against
as revealed from the IC
values (1.8-1.9 µg/mL). The compound
displayed a significant antifungal activity against
(0.82 µg/mL),
(1.2 µg/mL) comparing to authentic antibiotics. From the TEM microgram, the compounds
,
,
and
exhibited a strong deformation to the cellular entities, by interfering with the cell membrane components, causing cytosol leakage, cellular shrinkage and irregularity to the cell shape. In addition, docking study for the most promising antimicrobial tested compounds depicted high binding affinity against acyl carrier protein domain from a fungal type I polyketide synthase (ACP), and Baumannii penicillin- binding protein (PBP). Moreover, compound
showed high drug- likeness, and excellent pharmacokinetics, which needs to be in focus for further antimicrobial drug development. The most promising antimicrobial compounds underwent theoretical investigation using DFT calculation. |
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ISSN: | 1422-0067 1661-6596 1422-0067 |
DOI: | 10.3390/ijms222010979 |