Synthesis and biological activities of some Novel 2-Amino-(5 or 7-Substituted- 2-Oxoindolin-3-Ylidene) Benzoxazole-5-Carbohydrazide derivatives

Article abstract of DOI:10.2174/157018012800673029

A series of 2-amino-(5 or 7-substituted-2-oxoindolin-3-ylidene) benzoxazole-5-carbohydrazide derivatives were synthesized by treating 2-aminobenzoxazole-5-carbohydrazide with different substituted isatins. All the synthesized derivatives (VI a-l) were screened for their in vitro anticancer (against HeLa, IMR-32 & MCF-7 cancer cell lines), antioxidant (against DPPH radicals) and antimicrobial activities. The results of these studies showed the dose dependant anticancer, antioxidant and antimicrobial activities of the test compounds and the IC50 values of some compounds were comparable with their standard agent. The test compounds having substitution with different electron withdrawing groups at C-5 position showed more potent anticancer, antioxidant and antibacterial activities than those at C-7 position.

Full text of DOI:10.2174/157018012800673029

Letters in Drug Design & Discovery, 2012, 9, 625-632
625
Synthesis and Biological Activities of Some Novel 2-Amino-(5 or 7-Substit-
uted-2-Oxoindolin-3-Ylidene) Benzoxazole-5-Carbohydrazide Derivatives
G. Rajyalakshmi, A. Rama Narsimha Reddy and M. Sarangapani*
University College of Pharmaceutical Sciences, Kakatiya University, Warangal, Andhra Pradesh, 506 009, India
Received January 21, 2012: Revised March 07, 2012: Accepted March 14, 2012
Abstract: A series of 2-amino-(5 or 7-substituted-2-oxoindolin-3-ylidene) benzoxazole-5-carbohydrazide derivatives
were synthesized by treating 2-aminobenzoxazole-5-carbohydrazide with different substituted isatins. All the synthesized
derivatives (VI a-l) were screened for their in vitro anticancer (against HeLa, IMR-32 & MCF-7 cancer cell lines),
antioxidant (against DPPH radicals) and antimicrobial activities. The results of these studies showed the dose dependant
anticancer, antioxidant and antimicrobial activities of the test compounds and the IC50 values of some compounds were
comparable with their standard agent. The test compounds having substitution with different electron withdrawing groups
at C-5 position showed more potent anticancer, antioxidant and antibacterial activities than those at C-7 position.
Keywords: Isatin, Benzoxazole, Indole, Anticancer, Antioxidant, Antimicrobial.
INTRODUCTION
benzoxazole-5-carbohydrazide with different substituted
isatins (i.e. combining the above two mentioned pharmaco-
phores) for development of new anticancer, antioxidant,
antimicrobial agents.
The development of new antimicrobial and anticancer
therapeutic agents is one of the fundamental goals in
medicinal chemistry. An essential component of the search
for new leads in a drug designing program is the synthesis of
molecules, which are novel yet resemble known biologically
active molecules by virtue of the presence of some critical
structural features. Certain small heterocyclic molecules act
as highly functionalized scaffolds. These are known
pharmacophores of a number of biologically active and
medicinally useful molecules [1, 2].
RESULTS AND DISCUSSION
Chemistry
In the present study, twelve different novel 2-amino-(5 or
7-substituted-2-oxoindolin-3-ylidene)
benzo-xazole-5-
carbohydrazides (VI a-l) were prepared by treating 2-
aminobenzoxazole-5-carbohydrazide with different indole-
2,3-dione (isatin) derivatives. The preparation of the title
derivatives is outlined in Scheme 1. The physical data of the
all synthesized compounds were shown in Table 1. All the
synthesized compounds were purified by column chromato-
graphy using ethyl acetate, chloroform and methanol as
solvent and the reactions were monitored by TLC. The
chemical structures of the synthesized compounds (Table 1)
Previous reports reveal that benzoxazole (a pharma-
cophore) derivatives are biologically significant compounds
and are known to exhibit various biological activities such as
anticancer [3-5], antimicrobial [3-6], anti-HIV [4-6], and
dopamine D4 agonists [7]. Literature survey revealed that
isatin (1H-indole-2,3-dione) possess diverse chemothera-
peutic activities such as anticancer [8], antiviral [9], anti-
HIV [10], anti-mycobacterial [11], antibacterial [12], anti-
inflammatory [13], and anticonvulsant [14]. Among these
properties, anticancer & antimicrobial activities of this
moiety have been interestingly published by many
researchers [12, 15-17].
1
were confirmed by means of their IR, H NMR and mass
spectral analysis.
Biological Activities
The discovery of the role of free radicals in cancer,
diabetes, cardiovascular diseases, autoimmune diseases,
neurodegenerative disorders, aging and other diseases has
led to new medical insight [18-19]. Minimizing oxidative
damage may be an important approach to the primary
prevention or treatment of these diseases, since antioxidants
may stop the free-radical formation, or interrupt an oxidizing
chain reaction.
In Vitro Anticancer Activity
The anticancer activity of all the synthesized compounds
(VI a- VI l) was evaluated against HeLa, IMR-32 & MCF-7
cancer cell lines using MTT method and were almost equally
active against the three cell types tested. The IC50 values of
all the compounds including the intermediate were shown in
Table-2. Incubation of all synthesized compounds with
different cells resulted in a significant inhibition of growth of
the cells.
In view of above all, we have planned to synthesize some
novel 2-amino-(substituted-2-oxoindolin-3-ylidene) benzo-
xazole-5-carbohydrazides derivatives by treating 2-amino-
The IC50 values of all the synthetic test compounds were
found between 10.53 and 79.61µM and some of these IC50
values were comparable with known anticancer agent,
Cisplatin (IC50 value<11.20 µM). Among all the test
compounds, compound VI b (R1 substitution at C5 is F;
*Address correspondence to this author at the Professor of Pharmaceutical
Chemistry, University College of Pharmaceutical Sciences, Kakatiya
University, Warangal, A. P., 506 009, India; Tel: +91-870-2438844;
Mobile: +919291575876; E-mail: rajyaanreddy@gmail.com
1875-628X/12 $58.00+.00
© 2012 Bentham Science Publishers

626 Letters in Drug Design & Discovery, 2012, Vol. 9, No. 6
Rajyalakshmi et al.
H3COOC
Al(NO3)3
H3COOC
NO2
OH
AcOH, Ac2OH
OH
II
I
Na2S2O4
EtOH, H2O
H3COOC
N
O
H3COOC
CNBr
MeOH
NH2
OH
NH2
IV
III
NH2NH2.H2O
EtOH
H2NHNOC
N
NH2
O
V
O
O
R
N
H
EtOH, AcOH
N
NH2
O
O
NNHC
R
N
H
O
VI
Scheme 1. Synthesis of some novel 2-amino-(5 or 7-substituted-2-oxoindolin-3-ylidene) benzoxazole-5-carbohydrazides.
Table 1. Physical Data of All Synthesized Title Compounds (VI a-l)
N
NH2
O
R1
N
NH
C
O
N
O
H
R2
S. No
Compound
Mol. Formula
R1
R2
Mol .wt
% yield
m. p (o C)
1
2
VI- a
VI- b
VI- c
VI- d
VI- e
VI- f
VI- g
VI- h
VI- i
VI- j
VI- k
VI-l
C16H11O3N5
C16H10O3N5F
C16H10O3N5Cl
C16H10O3N5Br
C17H10O3N5
C16H10O5N6
C17H11O5N5
C18H13O5N5
C16H10O3N5Cl
C16H10O5N6
C17H10O3N5
C17H11O5N5
H
F
H
H
321
339
356
400
334
366
365
379
356
366
334
365
69
72
68
73
77
78
69
72
70
82
78
71
>300
260-262
308-310
270
3
Cl
Br
H
4
H
5
CH3
H
258-260
290-292
258-260
>300
6
NO2
H
7
COOH
H
8
COOCH3
H
9
H
H
H
H
Cl
238
10
11
12
NO2
CH3
COOH
230
232
210-212

Synthesis and Biological Activities
Letters in Drug Design & Discovery, 2012, Vol. 9, No. 6 627
Table 2.
Anticancer Activity of Synthesized Compounds Against HeLa, IMR-32 & MCF-7 Cancer Cells Using MTT Assay
N
NH2
O
R1
N
NH
C
O
N
O
H
R2
S. No
Compound
R1
R2
IC50 (µM) * (HeLa)
IC50 (µM) * (IMR-32)
IC50 (µM) * (MCF-7)
1
2
VI –a
VI- b
VI- c
VI-d
VI-e
H
H
H
61.18
12.64
16.11
13.33
50.89
27.64
55.7
64.57
13.80
14.42
15.18
42.50
29.61
56.9
58.24
10.53
13.82
12.61
45.75
26.92
60.11
79.61
30.9
F
Cl
3
H
4
Br
H
5
CH3
NO2
COOH
COOCH3
H
H
6
VI-f
H
7
VI-g
H
8
VI-h
VI-i
H
70.2
75.61
36.82
33.15
53.30
65.92
11.20
9
Cl
32.64
36.54
57.92
69.54
10.44
10
11
12
13
VI-j
H
NO2
CH3
COOH
34.84
48.24
63.82
9.64
VI-k
VI-l
H
H
Cisplatin
*Values are expresses as means (n=4).
R2=H), VI d (R1 at C5-is Br; R2=H), VI c (R1 at C5-is Cl;
R2=H), VI f (R1 at C5-is NO2; R2=H), and VI-i (R2 at C5-is
Cl; R1=H) having more potent anticancer activity against
three test cell types. From the Table 2, it was clear that
compounds having substitution at R1 (C-5 position in indole
ring) showed more anticancer activity than those at R2 (C-7
position in indole ring). This is not surprising, as C5-
substitution has previously been associated with increased
Table 3. Antioxidant Activity of Synthesized Compounds Using DPPH Method
N
NH2
O
R1
N
NH
C
O
N
O
H
R2
S. No
Compound
R1
R2
IC50 (µM) *
m/z
1
2
VI –a
VI- b
VI- c
H
F
H
H
40.92
19.47
24.50
20.62
38.92
27.85
49.63
57.18
37.08
38.65
36.28
44.05
8.64
323.1
341.09
357.06
401.01
337.12
368.09
367.09
381.11
357.06
401.01
368.09
367.09
3
Cl
H
4
VI-d
Br
H
5
VI-e
CH3
NO2
H
6
VI-f
H
7
VI-g
COOH
H
8
VI-h
COO CH3
H
9
VI-i
H
H
H
H
Cl
Br
NO2
10
11
12
15
VI-j
VI-k
VI-l
COOH
Ascorbic acid

628 Letters in Drug Design & Discovery, 2012, Vol. 9, No. 6
Rajyalakshmi et al.
biological activity for a range of indole- based compounds
[20, 21]. Comparatively, among R1 substituted compounds,
those substituted with electron withdrawing groups (-F, Cl,
Br, NO2 etc) are found to be potent anticancer agents.
(against Candida albicans, Aspergillus niger). The in vitro
antibacterial & antifungal properties of all the synthesized
compounds are presented in Tables 4 & 5 respectively and
the values were expressed in minimum inhibitory
concentrations (µg/ml).
Antioxidant Activity Using DPPH Method
The newly synthesized compounds significantly inhibited
the growth of bacteria and most of the MIC values were
found between 20 and 100 mg/ml indicating their potent to
moderate antibacterial activity. Among all the compounds,
compounds VI d, VIb & VI c showed good antibacterial
activity against tested gram positive and negative bacteria
(Table 4).
In vitro antioxidant or free radical scavenging activity of
all the synthesized compounds was evaluated using DPPH as
a free radical and the results of this study were showed in
Table 3.
The results of this study revealed that all the synthesized
compounds are significantly scavenged the DPPH free
radicals. The IC50 values of all the test compounds were
found between 19.47 and 57.18µM. Similar to the anticancer
activity, compound VI b (R1 substitution at C5 is F; R2=H),
VI d (R1 at C5-is Br; R2=H), VI c (R1 at C5-is Cl; R2=H), VI
f (R1 at C5-is NO2; R2=H), and VI-i (R2 at C5-is Cl; R1=H)
having more potent antioxidant activity. This may be due to
the increased lipophilicity of molecules because of
substitution with electronegative atom such as chloro/bromo
at the C5 position of the aromatic ring [22]. Among all, the
test compounds having substitution at R1 (C-5 position in
indole ring) showed more antioxidant activity than those at
R2 (C-7 position in indole ring).
Compounds which showed MIC of >100 µg/ml or above
have not been included for the discussion. The synthetic
compounds significantly inhibited the growth of tested fungi
(Table 3) and the MIC values were found between 30 & 100
µg/ml (Table 5).
EXPERIMENTAL
General
Melting points (mp) were determined in open capillaries,
o
using Toshniwal melting point apparatus, expressed in C
and are uncorrected. The IR spectra of the compounds were
recorded on thermo Nicolet Nexus 670S series, FT-IR
spectrometer using KBr disc.1H NMR were recorded on a
Avance-300 MHz instrument using TMS as an internal
standard(chemical shifts in δ,ppm), mass spectra were
recorded on a LC-MSD-Trap-SL. The purity of the
compounds was checked on silica gel-coated aluminum
In Vitro Antimicrobial Activity
The newly synthesized 2-amino-(5 or 7-substituted-2-
oxoindolin-3-ylidene) benzo-xazole-5-carbohydrazides were
screened for antibacterial (against Escherichia coli,
Salmonella typhi, Bacillus subtilis) and antifungal activity
Table 4. MIC Values of (µg/ml) of Synthesized Compounds Against Tested Bacteria
N
NH2
O
R1
N
NH
C
O
N
O
H
R2
S. No
Compound
E. coli*
S. typhi
B. subtilis
1
2
VI –a
VI- b
VI- c
90
25
85
35
95
30
3
30
25
35
4
VI-d
20
20
25
5
VI-e
75
80
80
6
VI-f
40
50
60
7
VI-g
>100
>100
50
95
90
8
VI-h
>100
60
>100
65
9
VI-i
10
11
12
13
VI-j
60
55
60
VI-k
85
90
85
VI-l
>100
9.0
100
9.0
>100
18
Ciprofloxacin
Minimum inhibitory concentration (MIC) of compounds were expressed as µg/ml (n=3).

Synthesis and Biological Activities
Letters in Drug Design & Discovery, 2012, Vol. 9, No. 6 629
Table 5. Antifungal Activity of All the Synthesized Compounds Against Tested Fungi
N
NH2
O
R1
N
NH
C
O
N
O
H
R2
S. No
Compound
C. albicans*
A. niger*
1
2
3
4
5
6
7
VI –a
VI- b
VI- c
VI-d
VI-e
VI-f
75
30
35
30
60
40
95
80
30
30
35
55
40
VI-g
100
8
VI-h
VI-i
>100
60
>100
50
9
10
11
12
13
VI-j
50
50
VI-k
60
70
VI-l
90
100
2.5
Nystatin
2.0
Minimum inhibitory concentration (MIC) of compounds were expressed as µg/ml (n=3).
sheets (Merck, 1.005554, silica gel HF254–361,Type 60,
0.25 mm, Darmstadt, Germany) by thin-layer chromato-
graphy (TLC). TLC was performed on silica gel G for TLC
(Merck) and spots were visualized by iodine vapour or by
irradiation with ultraviolet light (short wave length, 254 nm).
Column chromatography was performed by using Qualigen’s
silica gel for column chromatography (60–120 mesh).
Mumbai, India), and seeded in 96-well plates (tarsons,
India).
Chemistry - General Procedures
Synthesis of 4-Carbomethoxy-2-nitrophenol (II)
To a solution of aluminium nitrate (40grms) in acetic
acid- acetic anhydride (1:1) mixture (160ml), was added an
appropriate phenol (I, 40grms) in small portions, while
cooling and shaking occasionally. The reaction mixture was
left at room temperature for 1.5 hours while shaking the
contents intermittently to complete the nitration.
Chemicals
All the solvents, reagents and catalysts used are AR
grade. Isatin, fetal bovine serum (FBS), Dulbecco’s modified
eagle’s medium (DMEM), penicillin, amphotericin B, and
streptomycin were purchase from Himedia (Mumbai, India).
DPPH (α,α-diphenyl-β-picryl hydrazyl),3-(4, 5-Dimethyl-
thiazol-2-yl)-2, 5- diphenyltetrazolium bromide (MTT) was
purchased from Sigma Chemical Company (St. Louis, MO,
USA). Substituted isatins were prepared by the procedures
reported in the literature [23].
The resulting brown solution was diluted to complete the
nitration. The resulting brown solution was diluted with ice-
cold water and acidified with concentrated Nitric acid to get
a bulky, yellow precipitate. It was filtered washed with small
quantity of methanol and purified by recrystallization from
alcohol to get a yellow crystalline solid, yield (85%), m.p
73OC.
Synthesis of 4-carbomethoxy-2-aminophenol (III)
Cell Cultures
4-carbomethoxy-2-nitrophenol (II, 10 grams) was
dissolved in boiling alcohol (50%, 100ml) and sodium
dithionite was added to this boiling alcohol solution until it
becomes almost colourless. Then the alcohol was reduced to
one-third of its volume by distillation and the residual liquid
was triturated with crushed ice. The resulting colourless,
shiny product was filtered, washed with cold water and dried
in the air. Its purification was effected by recrystallization
from benzene to get colourless, shiny scales,yield,(5.1 g;
60%) m.p 143OC.
The HeLa (cervical), IMR-32 (neuronal) & MCF-7
(breast) cancer cell lines were purchased from National
Centre for Cell sciences (NCCS), Pune, India. These cell
lines were grown and maintained using suitable (DMEM)
media and were grown in culture medium supplemented with
10% fetal bovine serum, 1% L-glutamine and 1% penicillin-
streptomycin-amphotericin B antibiotic solution. Cells were
seeded in 25cm2 tissue culture flasks (tarsons, India), at 250
000 cells/flask in a total volume of 9ml. When confluent, all
the cells were trypsinized (using Trypsin-EDTA, HiMedia,

630 Letters in Drug Design & Discovery, 2012, Vol. 9, No. 6
Rajyalakshmi et al.
Synthesis of methyl-2-aminobenzoxazole-5-carboxylate
(IV)
ppm: 7.16-7.18 (d, 1H, Ar-H), 7.55-7.60 (m, 3H, Ar-H),
7.68-7.73 (d, 2H [Ar-H], 2H [-NH2]), 11.99 (s, 1H, indole
NH),13.72 (s, 1H, NHCO); ESI: m/z value 363.0.
4-Carbomethoxy-2-aminophenol (III, 1.3 moles) was
dissolved in 1lit. methyl alcohol and cooled the solution by
adding chopped ice. A cold suspension of Cyanogenbromide
(1.5 moles) in 1lit.of water was added over a period of 5min
with rapid stirring.
2-amino-(7-nitro-2-oxoindolin-3-ylidene) benzoxazole-5-
carbohydrazides (VI j)
IR υ (cm-1): 3403 (N-H),3255 (-NH2), 1746 (C=O), 1675
1
(C=O), 1553(C=N), 1321 (C-O-C), 1257 (C-N); H NMR
The reaction mixture was stirred for 0.75hrs at room
temperature, solid Sodium bicarbonate (1.3 moles) in small
portions over a period of 1.5 hrs was added to bring the pH
6.5 -7.0. Stirring was continued for another 1hour. The solid
was separated by filtration, washed with cold water and on
recrystallization from ethyl alcohol has resulted white solid,
yield 70% and M.P is 238OC.
(DMSO-d6) δ ppm: 7.19-7.23 (t, 1H, Ar-H), 7.35-7.37 (d,
2H, Ar-H), 7.49-7.52 (m, 3H [Ar-H], 2H [-NH2]), 10.41 (s,
1H, indole NH),11.35 (s, 1H, NHCO); ESI: m/z value 363.0.
BIOLOGICAL ACTIVITIES
Evaluation of In Vitro Anticancer Activity
Synthesis of 2-aminobenzoxazole-5-carbohydrazide (V)
MTT [3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetra-
zolium bromide] assay was used to evaluate the in vitro
anticancer activity of all the synthesized compounds against
HeLa, IMR-32 & MCF-7 cancer cell lines [24]. Stock
solutions of all the synthetic compounds were prepared in
DMSO and were serially diluted with complete growth
medium to obtain working test solution of required
concentrations (having < 1% DMSO). The cell suspension of
1 x105 cells / ml was prepared in complete DMEM growth
medium. The 100 µl of cell suspension was added to each
well of the 96-well tissue culture plates. The cells were
allowed to grow in CO2 incubator (37 OC, 5% CO2, 90%
relative humidity) for 24 h. The test materials in complete
growth medium (100 µL) were added after 24 h incubation
to the wells containing cell suspension. After 48 hr of
treatment with different concentrations of test compounds,
the cells were incubated with MTT (2.5 mg/ ml) for 2 h. The
medium was then removed and 100 µl of DMSO were added
into each well to dissolve formazan crystals, the metabolite
of MTT. After thoroughly mixing, the plate was read at
490nm for optical density that is directly correlated with cell
quantity.
To 0.1mol of compound IV in absolute ethanol (20ml),
hydrazine hydrate (99%,0.1 mol) was added followed by a
catalytic amount of glacial acetic acid (3 drops). Then the
mixture was refluxed for 6 hrs. Excess solvent was removed
by distillation and poured on to crushed ice to give a white
color solid (V) and recrystallized from ethanol
Synthesis of 2-amino-(2-oxoindolin-3-ylidene) benzoxa-
zole-5-carbohydrazide (VI)
To a warm solution of 2-aminobenzoxazole-5-carbohy-
drazide (V)(0.01mol) in absolute ethanol(15ml) was added
the appropriate indole-2,3-dione(Isatin; 0.01mol) in presence
of glacial acetic acid and the reaction mixture was heated
under reflux for 8-12 hr, then allowed to cool to room
temperature. The solid product thus formed was filtered,
thoroughly washed with cold water, dried and recrystallized
from ethanol and purified from column chromatography
(Ethylacete: hexane ). The chemical structures of the
synthesized compounds (Table 1) were confirmed by means
of their IR, 1H NMR and mass spectral analysis.
Spectral Data of Some Synthesized Compounds
Evaluation of Antioxidant Activity
2-amino-(5-fluoro-2-oxoindolin-3-ylidene) benzoxazole-5-
carbohydrazides (VI b)
We have used a stable free radicalα,α-diphenyl-β-picryl
hydrazyl (DPPH) for the evaluation of antioxidant activity,
at the concentration of 0.2 mM in methanol [25]. To the 0.1
ml of test compound (at different concentrations), 1.5 ml of
methanol and 0.5 ml of DPPH solution were added, mixed
thoroughly and absorbance (OD) was read at 517 nm against
blank. The % reduction of free radical concentration (OD)
with different concentration of test compounds was
calculated and was compared with standard, ascorbic acid.
The results were expressed as IC50 values (the concentration
of test required to scavenge 50% free radicals).
IR υ (cm-1): 3458 (N-H of Indole), 3249 (-NH2), 1700
(C=O), 1690 (C=O), 1530 (C=N), 1299 (C-O-C), 1140 (C-
1
N); H NMR (DMSO-d6) δ ppm: 7.20 (s, 1H, Ar-H), 7.40-
7.42 (d, 1H, Ar-H), 7.49-7.59 (m, 3H, Ar-H), 7.67 (s, 1H,
Ar-H), 7.71 (s, 2H, NH2), 11.38 (s, 1H, indole NH), 13.93 (s,
1H, NHCO); ESI: m/z value 340.0.
2-amino-(5-bromo-2-oxoindolin-3-ylidene) benzoxazole-5-
carbohydrazides (VI d)
IR υ (cm-1): 3454 (N-H of Indole), 3229 (-NH2), 1680
(C=O), 1615 (C=O), 1526 (C=N), 1290 (C-O-C), 1145 (C-
1
N); H NMR (DMSO-d6) δ ppm: 6.91-6.93 (d, 1H, Ar-H),
In vitro Antimicrobial Activity
7.49-7.58 (m, 3H, Ar-H), 7.67-7.71 (d, 2H [Ar-H], 2H [-
NH2]), 11.47 (s, 1H, indole NH),13.85 (s, 1H, NHCO); ESI:
m/z value 401.0.
All the synthesized compounds were screened for their in
vitro antibacterial and antifungal activities by the broth
micro-dilution procedures and principles of the Clinical and
Laboratory Standards Institute (CLSI) [26, 27]. Minimal
inhibitory concentrations for each compound were
investigated against standard bacterial strains; E. coli and
S.typhi (gram negative); B. subtilis (gram positive); C.
2-amino-(5-nitro-2-oxoindolin-3-ylidene) benzoxazole-5-
carbohydrazides (VI f)
IR υ (cm-1): 3139 (N-H), 1707 (C=O), 1672 (C=O), 1529
1
(C=N), 1342 (C-O-C), 1292 (C-N); H NMR (DMSO-d6) δ

Synthesis and Biological Activities
Letters in Drug Design & Discovery, 2012, Vol. 9, No. 6 631
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1-yl)acetamido]-2-(p-substituted phenyl) benzoxazoles.
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Arch.
A new series of 2-amino-(substituted-2-oxoindolin-3-
ylidene) benzoxazole-5-carbohydrazides derivatives were
successfully synthesized and were screened for their in vitro
anticancer, antioxidant and antimicrobial activities. The
present study results indicated that all the synthesized 2-
amino-(5 or 7-substituted-2-oxoindolin-3-ylidene) benzo-
xazole-5-carbohydrazides showed significant moderate to
potent in vitro anticancer, antioxidant and antimicrobial
activities.
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a)
It was observed that most of the title compounds
which are substituted with electron withdrawing
groups showed better biological activities than those
of non- substituted derivatives. These electron
withdrawing groups may decrease electron density on
benzene ring through resonance effect.
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b)
The biological activities of test compounds were
more with compounds having C5-substitution (on
isatin moiety) than C7- substitution, especially with
different halides (electron withdrawing groups).
Therefore synthesis of 2-amino-(substituted-2-oxoin-
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benzoxazole-5-carbohydrazides
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None declared.
ACKNOWLEDGEMENTS
The first author is thankful to University Grants
Commission (UGC), New Delhi, India for providing the
RGNF (Rajiv Gandhi National Fellowship) Junior Research
Fellowship. The authors are thankful to central
instrumentation centre, Kakatiya University, Warangal and
Laila Impex, Vijayawada, India for providing the spectral
data.
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