3108
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J = 8.0 Hz, 1H), 7.56 (d, J = 7.0 Hz, 1H), 7.61 (dd, J = 4.5 Hz, 1H), 8.16 (s, 1H), 8.34
(d, J = 7.5 Hz, 1H), 8.82 (d, J = 4.5 Hz, 1H), 9.15 (s, 1H), 12.43 (s, 1H, D2O
exchangeable), 12.88 (s, 1H, D2O exchangeable). 13C NMR (125 MHz, DMSO-d6)
(d, ppm) 16.43, 116.00, 117.74, 122.07, 123.53, 124.78, 128.20, 130.95, 131.06,
136.27, 141.06, 144.67, 149.24, 152.82, 157.37, 163.29, 184.11. ESIMS (m/z):
Calcd 307.30, found 308.10 (M++H), in accordance with MF C17H13N3O3.
4((11E)-2-hydroxy-N0-(5-hydroxy-2-methyl-1-oxonaphthalen-4(1H)-ylidene)
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benzohydrazide), yield: 66%, UV–vis (DMSO): k nm: (373.5). IR (KBr disk), m,
cmꢀ1: 3269–3234 (–OH), 1683, 1641 (–C@O), 1604 (C@N), 1280 (C–O), 1055 (N–
N). 1H NMR (500 MHz, DMSO-d6) (d, ppm) 2.12 (s, 3H, –CH3), 6.99 (dd, J = 7.5 Hz,
1H), 7.03 (d, J = 8.0 Hz, 1H), 7.23 (d, J = 8.0 Hz, 1H), 7.47 (dd, J = 7.5 Hz, 1H), 7.51
(dd, J = 8.0 Hz, 1H), 7.60 (d, J = 7.5 Hz, 1H), 7.88 (d, J = 7.5 Hz, 1H), 7.89 (s, 1H),
11.42 (s, 1H, D2O exchangeable), 12.31 (s, 1H, D2O exchangeable), 12.87 (s, 1H,
D2O exchangeable). 13C NMR (125 MHz, DMSO-D6) (d, ppm) 17.08, 116.68,
117.40, 118.27, 119.94, 122.52, 124.40, 130.78, 131.39, 131.50, 134.45, 141.70,
157.61, 157.80, 164.37, 184.64. ESIMS (m/z): Calcd 322.32, found 322.09 (M+), in
accordance with MF C18H14N2O4.
5
((11E)-N0-(5-hydroxy-2-methyl-1-oxonaphthalen-4(1H)-ylidene)benzohyd-
razide), yield: 58%, UV–vis (DMSO): k nm:(346.5). IR (KBr disk),
, cmꢀ1: 3195–
m
3157 (–OH), 1680, 1645 (–C@O), 1599 (C@N), 1284 (C–O), 1051 (N–N). 1H NMR
(500 MHz, DMSO-d6) (d, ppm) 2.12 (s, 3H, –CH3), 7.24 (d, J = 8.0 Hz, 1H), 7.49 (t,
J = 7.5 Hz, 1H), 7.58 (d, J = 7.5 Hz, 1H), 7.67 (t, J = 7.5 Hz, 3H), 8.01 (d, J = 7.0 Hz,
2H), 8.22 (s, 1H),12.33 (s, 1H, D2O exchangeable), 12.98 (s, 1H, D2O
exchangeable). 13C NMR (125 MHz, DMSO-d6) (d, ppm) 16.90, 116.70, 118.16,
122.51, 125.45, 128.98, 131.44, 132.71, 133.02, 141.27, 144.68, 157.86, 165.22,
184.72. ESIMS (m/z): Calcd 306.32, found 307.12 (M++H), in accordance with MF
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experiment was repeated at least three times. Test compounds were dissolved
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39. Docking studies: All the docking calculations were carried out with AutoDock
4.0 software to analyze ligand interactions with the crystal structure binding
site of p50-NFêB obtained from PDB ID (1NFK). AutoDock calculates a rapid
energy evaluation through pre-calculated grids of affinity potentials with a
variety of search algorithms to find appropriate binding positions. The active
site of the enzyme was defined to include residues 59–71. The 3-D grid box has
been generated with a grid centre co-ordinates comprising of grid spacing
0.375 Å and 60 ꢁ 60 ꢁ 60 point size considering active site residues included
within it. Stable docking conformation of compounds achieved by
implementing energy minimization parameter AMBER force field until the
gradient convergence value of 0.05 Kcal/mol was reached with distance-
dependent dielectric function (€=4r). New designed all plumbagin analogs, as
well as PL were placed in grid box of p50 for docking process. Customized
docking parameters were set in AutoDock for best results for understanding
interaction studies with new designed compounds. Parameter settings were
set to 1500 iterations, 50 population sizes, 100.0 kcal/mol of energy threshold
for pose generation, 300 simplex evolution steps and 1.0 neighbor distance
factor. For preparing the AutoDock docking parameter file we used default
settings (genetic algorithm parameters: population size = 150, number of
energy evaluations = 2.5 ꢁ 107, rate of gene mutation = 0.02, rate of
crossover = 0.8, maximum number of generations = 27000, number of GA
runs = 10, initial dihedrals were randomly specified, elitism value was set to 1).
Prior to docking, total Kollman and Gasteiger charges were added to the
protein and the ligand. For each compound, the most stable docking model was
selected based upon confirmation of best scored predicted by the AutoDock
scoring function.
31. Chen, Z. F.; Tan, M. X.; Liu, Y. C.; Peng, Y.; Wang, H. H.; Liu, H. G.; Liang, H. J.
Inorg. Biochem. 2011, 105, 426.
32. Synthesis of Plumbagin Hydrazides: The ligands (2–5) was synthesized by
condensation of equimolar quantities of plumbagin and isonicotyl, nicotyl,
salicyl and benzoyl hydrazide respectively in methanol in presence of trifluoro
acetic acid as catalyst with continuous stirring at 60 °C for 4 h. The precipitated
compounds were washed 2–3 times with cold methanol, dried under vacuum
and purified by column chromatography using chloroform: methanol (9:1) as
solvent system.
2
((11E)-N0-(5-hydroxy-2-methyl-1-oxonaphthalen-4(1H)-ylidene)isonicotin-
ohydrazide), yield: 68%, UV–vis (DMSO): k nm:(344.5). IR (KBr disk),
m
, cmꢀ1
:
H
3213–3109 (–OH), 1672, 1640 (–C@O), 1604 (C@N), 1282 (C–O), 1058 (N–N). 1
NMR (500 MHz, DMSO-d6) (d, ppm) 2.13 (s, 3H, –CH3), 7.27 (d, J = 10.0 Hz, 1H),
7.52 (t, J = 9.5 Hz, 1H), 7.61 (d, J = 9.0 Hz, 1H), 7.92 (d, J = 6.0 Hz, 2H), 8.18 (s, 1H),
8.83 (d, 7.0 Hz, 2H), 12.52 (s, 1H, D2O exchangeable), 12.88 (s, 1H, D2O
exchangeable). 13C NMR (125 MHz, DMSO-d6) (d, ppm) 16.43, 115.91, 117.83,
122.16, 124.84, 130.98, 131.23, 139.43, 141.25, 150.21, 157.42, 163.44, 184.13.
ESIMS (m/z): Calcd 307.30, found 308.10 (M++H), in accordance with MF
C17H13N3O3.
3((11E)-N0-(5-hydroxy-2-methyl-1-oxonaphthalen-4(1H)-ylidene)nicotinohy-
drazide), yield: 64%, UV–vis (DMSO): k nm:(351.5). IR (KBr disk), m
, cmꢀ1: 3194–
3157 (–OH), 1680, 1647 (–C@O), 1589 (C@N), 1274 (C–O), 1040 (N–N). 1H NMR
(500 MHz, DMSO-d6) (d, ppm) 2.10 (s, 3H, –CH3), 7.23 (d, J = 8.0 Hz, 1H), 7.48 (t,