DESIGN, DOCKING AND SYNTHESIS OF NOVEL BROMO ISATIN INCORPORATED ISOXAZOLE DERIVATIVES AS VEGFR-2 INHIBITORS
By: Radhika, T
.
Contributor(s): Saisre, K.
Publisher: M P Innovare Academic Sciences Pvt Ltd 2019Edition: Vol.11(4).Description: 1-7p.Subject(s): PHARMACEUTICSOnline resources: Click here
In:
International journal of pharmacy and pharmaceutical scienceSummary: Objective:
To design, synthesize,
in vitro
Vascular Endothelial Growth Factor Receptor (VEGFR
-2) assay, antiproliferative activity an Absorption
,
Distribution, Metabolism, Excretion and Toxicity (A
DMET) studies of some novel bromoisatin incorporate
d isoxazole derivatives.
Methods:
Designed compounds were synthesized by the condensa
tion of different 3-aryl-5-methylisoxazole-4-carboh
ydrazides (5a-h) with 5-bromoisatin
to give the target molecules. To predict the affini
ty and activity of the ligand molecule the docking
program GOLD 3.1 was employed to generate different
bioactive binding poses of designing molecules at t
he active site of protein VEGFR-2. All the synthesi
zed compounds were characterized based on the spect
ral
and elemental analysis data. Antiproliferative acti
vity performed against Human Umbilical vein endothe
lial cells (HUVEC cell line).
Results:
All the synthesized compounds showed the characteri
stic peaks in FTIR,
1
H, C
13
NMR and Mass spectral analysis. In molecular dockin
g, all
the synthesized compounds (6a-j) exhibited high fit
ness scores with minimum three bonding interaction
with the active site VEGFR-2 kinase. In
in-
vitro
, VEGFR-2 kinase assay, compounds 6a, 6b, 6d and 6e
exhibited more than 70% inhibition at a single dos
e concentration of 5μM. In
antiproliferative assay against HUVEC cell lines, co
mpounds 6d and 6e exhibited potent activity with IC
50
values in nanomolar concentrations.
ADMET results of 6a, 6b, 6d and 6e are quite promis
ing with least hepatotoxicity and good bioavailabil
ity.
Conclusion:
The derivatives were synthesized in quantitative yi
elds. New derivatives posses antiproliferative acti
vity, least hepatotoxicity and good
bioavailability.
| Item type | Current location | Call number | Status | Date due | Barcode | Item holds |
|---|---|---|---|---|---|---|
Articles Abstract Database
|
School of Pharmacy Archieval Section | Not for loan | 2020899 |
Objective:
To design, synthesize,
in vitro
Vascular Endothelial Growth Factor Receptor (VEGFR
-2) assay, antiproliferative activity an Absorption
,
Distribution, Metabolism, Excretion and Toxicity (A
DMET) studies of some novel bromoisatin incorporate
d isoxazole derivatives.
Methods:
Designed compounds were synthesized by the condensa
tion of different 3-aryl-5-methylisoxazole-4-carboh
ydrazides (5a-h) with 5-bromoisatin
to give the target molecules. To predict the affini
ty and activity of the ligand molecule the docking
program GOLD 3.1 was employed to generate different
bioactive binding poses of designing molecules at t
he active site of protein VEGFR-2. All the synthesi
zed compounds were characterized based on the spect
ral
and elemental analysis data. Antiproliferative acti
vity performed against Human Umbilical vein endothe
lial cells (HUVEC cell line).
Results:
All the synthesized compounds showed the characteri
stic peaks in FTIR,
1
H, C
13
NMR and Mass spectral analysis. In molecular dockin
g, all
the synthesized compounds (6a-j) exhibited high fit
ness scores with minimum three bonding interaction
with the active site VEGFR-2 kinase. In
in-
vitro
, VEGFR-2 kinase assay, compounds 6a, 6b, 6d and 6e
exhibited more than 70% inhibition at a single dos
e concentration of 5μM. In
antiproliferative assay against HUVEC cell lines, co
mpounds 6d and 6e exhibited potent activity with IC
50
values in nanomolar concentrations.
ADMET results of 6a, 6b, 6d and 6e are quite promis
ing with least hepatotoxicity and good bioavailabil
ity.
Conclusion:
The derivatives were synthesized in quantitative yi
elds. New derivatives posses antiproliferative acti
vity, least hepatotoxicity and good
bioavailability.
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