Background::
Most of the currently available pharmaceutical drugs are either natural
products or analogues of natural products. Flavonoids are plant based natural polyphenolic
compounds which exhibit a wide range of biological activities. Chrysin, a natural flavone, exhibits
several biological activities like antiallergic, anti-inflammatory and anticancer. Many efforts were
made to enhance the biological activity of chrysin. In continuation of our work on synthetic
modifications of chrysin, amino-alcohol containing heterocyclic moiety is linked to chrysin at C (7)
position to enhance its biological activity.
Methods::
A series of new C (7) modified analogues of chrysin (3a-k) have been designed and
synthesized in two steps. Chrysin, on reacting with epichlorohydrin in the presence of K2CO3 in
DMF gave epoxide (2) which was made to react with cyclic secondary amines in the presence of
LiBr to form the designed products (3a-k). All the synthesized compounds (3a-k) were well
characterized by 1H NMR, 13C NMR and mass spectral data. The synthesized analogues (3a-k) were
screened for their in vitro biological activities against a panel of bacterial and fungal strains.
Molecular docking studies were also performed on these compounds with E. coli FabH (1HNJ) and
S. cerevisiae (5EQB) enzymes, to support the observed biological activities.
Results::
A series of new 2-hydroxy 3-amino chrysin derivatives (3a-k) were synthesized in two
steps, starting with chrysin and their structures were characterized by spectral analysis. In vitro
biological activities of these analogues against a panel of bacterial and fungal strains indicated that
some of the derivatives manifested significant activities compared to standard drugs. Molecular
docking and binding energy values were also correlated with experimental antimicrobial screening
results. Lipinski’s “rule of five” is also obeyed by these analogues (3a-k) and exhibit drug-likeness.
Conclusion::
In the present study, a series of new C (7) modified chrysin analogues (3a-k) were
synthesized and tested for their in vitro antimicrobial activities. These biological studies indicated
that some of the derivatives exhibited moderate to good antimicrobial activities compared to
standard drugs. Molecular docking studies performed on these compounds correlated with the
experimental antimicrobial activities. The results obtained in the study will be useful in establishing
new drug entities to control the pathogenic epidemics.
DNA-binding, molecular docking studies and biological activity studies of ruthenium(ii) polypyridyl complexes
