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Design, Synthesis, Docking Studies And Biological Evaluation Of 6-

Substituted 2-(3-Substituted 5-Methyl 1H-Pyrazol-1yl) Benzothiazole
Derivatives As Antimicrobial Agents

Article · September 2019

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1(2), 2019, 1-9

Current Trends in Pharmacy and

Pharmaceutical Chemistry
http://e-currentscience.com/journal/e/CTPPC
Research Article

Design, Synthesis, Docking Studies And Biological Evaluation Of 6-Substituted 2-(3-

Substituted 5-Methyl 1H-Pyrazol-1yl) Benzothiazole Derivatives As Antimicrobial
Agents.

Smita Pawar*,Priyanka Mohite, Priya Zori, Amol Kale

Department of Pharmaceutical Chemistry, PDEA’s S.G. R.S College of Pharmacy, Saswad,

Pune-412 301, Maharashtra, India

*Corresponding author E-mail address: sjpawar4477@gmail.com

INTRODUCTION Pyrazole and fused heterocyclic pyrazole

Its alarming that increased resistance to the
existing antimicrobial drugs due to
invasion of the pathogenic microorganisms
which leads to a major health hazard.1,2
The occurrence of bacterial resistance to
various antibacterial agents such as
quinolones,chloramphenicols,
sulphonamides, glycopeptides,
nitroimidazoles, β-lactams,tetracyclines,
and macrolides areof prime concern.This
increased multidrug resistant bacterial
infectionsnecessitates the design of novel
antimicrobial agents acting on novel
targets. In recent years’ heterocyclic
compounds and derivatives have
fascinated strong interest due to their
effective biological and pharmacological
assets. Benzothiazole derivatives are one
of the versatile class of compound. It is
unique scaffold for further molecular
exploitation to synthesise novel
antibacterial agents. It is well documented
that it shows numerous biological
activities such as antimicrobial 3,
anticancer 4, antileishmanial 5, anti-
diabetic and antifungal 6 activities.
derivatives are an interesting class of
heterocycles due to their synthetic and
effective biological activities. Pyrazoles
are also known to holds potent and
selective inhibitory action against DNA
gyrase7,8. Thus, it is revealed from the
literature that benzothiazole, as well as
pyrazole derivatives, hold diverse
pharmacological activity. DNA gyrase is a
bacterial enzyme that catalyses the
introduction of negative supercoils in a
closed-circular DNA using the energy of
the ATP hydrolysis. Since it was found
only in prokaryotes and is vital for their
survival; it has become an attractive target
for antibacterial agents 9 Thus, we aim to
incorporate both leads together with the
expectation to have better antimicrobial
potential. Thus, this paper reports the
synthesis and antimicrobial activity of 6-
substituted 2-(3-substituted,5-methyl 1H-
pyrazol-1-yl)benzo[d]thiazole. The
molecular docking studies were also
carried out to check the possible
interactions of compounds with DNA
gyrase active pocket. exploration to

1
 Design, Synthesis, Docking Studies And Biological Evaluation ……. Smita Pawar et al
synthesise novel compound. Substituted
benzothiazoles fused with pyrazole have
been shown to possess antibacterial,
antifungal and antimicrobial activity.
MATERIALS AND METHODS
All the reagents and chemicals used were
of analytical grade. The progress of the
reaction and purity of all the synthesized
compounds was monitored by TLC. IR
spectra were recorded on Shimadzu FTIR
8400S by using KBr, and the NMR spectra
were recorded in NMR Varian-Mercury
300 MHz spectrometer in CDCl3 and
values are expressed in ppm.
Antimicrobial activity
Zone of inhibition
Thecompounds were evaluated for the
antibacterial10 and antifungal11activity by
the cup plate method against gram-positive
bacteria B. subtilis (ATCC 6633)S. aureus
(ATCC 9144) and gram-negative bacteria
E. coli (ATCC 25922) andP. aeruginosa
(ATCC 9027), at the concentration: 50
μg/ml, 100 μg/ml, 150 μg/ml in DMSO.
The bacterial strains were obtained from
NCL, and fungal strains were obtained
from the department of microbiology of
Waghire College, Saswad. For
antibacterial and antifungal study, the
ciprofloxacin and fluconazole150 μg/ml
respectively were used as reference drugs.
The nutrient agar medium containing
peptone (1%), beef extract (0.5%), sodium
chloride (0.8%) and agar (2.5%), in
distilled water were used for bacterial sub-
cultured. The solution was sterilized for 20
min at 15 psi pressure in an autoclave at
120 °C. The basal medium 15-20 ml was
poured into the sterile Petri dishes. After
the solidification of the medium, the
suspension of the organism was spread by
the spreader and holes of 6 mm diameter
were bored to form cups with the help of a
sterile cork borer. To this cup 50μg/ml,
100 μg/ml, 150 μg/ml of (solvent DMSO)
of the test compounds were added by the
micropipette. The Petri dishes was kept in
a refrigerator to facilitate the diffusion of
solvent for about 2 hrs. The extent of
inhibition was measured in mm after
incubation at 37 °C for 48 h.
Minimum inhibitory concentration
The Minimum inhibitory concentration
study was performed by broth dilution
method as follows:
Broth dilution method
The broth dilution was performed by using
microtiter plates. The nutrient broth
(double strength) was prepared using
peptone (1%), beefextract (0.5%),
sodiumchloride (0.8%). The double
strength nutrient broth was used for MIC.
All the compounds were dissolved in
DMSO to give a concentration of 200
μg/ml. Two-fold dilutions of test and
standard compounds were prepared in
double strength nutrient broth. The stock
solution was serially diluted to give
concentration of 200-3.12 μg/ml in
nutrient broth. First row (A) of microtiter
plate was used to check the sterility of
medium and as a negative control. Second
row (B) of microtiter plate was used to
check the suitability of the medium for the
growth of test microorganism and viability
of the inoculum and as positive control.
Fill each row (From C-H) of the microtiter
plate with 100μlfrom each of the tubes
containing the corresponding
concentrations(200-3.12 μg/ml).
Themicrotiter plate was then incubated at
37 °C for 24 hrs for bacteria and 48 hrs for
fungi .12
Docking studies
The docking process was carried out to
analyse the possible interactions between
newly synthesized compounds and the
selected cavity of the DNA gyrase
2
 Design, Synthesis, Docking Studies And Biological Evaluation ……. Smita Pawar et al
enzyme. The high-resolution (2.30 A °) X-
ray structure of DNA gyrase complexed
with pyrazolthiazole (PDB code 3G75)
was imported into Vlife 3.5 MDS, and the
ligand was extracted to leave a cavity. The
protein was a dimer which was converted
into monomer by deleting one-chain.
Water molecules were removed from the
monomer. The hydrogens were added in
the protein molecule, and energy was
minimized using Merck Molecular Force
Field (MMFF). The structure of
pyrazolthiazole extracted from the 3G75
protein was energy minimized using
MMFF. The conformers of
pyrazolthiazole, were generated and
docked back into the corresponding
binding pocket to determine the ability of
the Biopredicta tool to reproduce the
orientation and position of the inhibitor
observed in the crystal structure. The
docked conformations were further scored
using dock score. Conformers of
individual 3D optimized synthesized
compounds F1 to F10 were generated
using ‘systematic conformational search
method’. In a systematic conformational
search, a set of rotatable bonds is
identified by the user and for each of these
bonds; all possible conformers are
examined as a function of each other. For
each conformer generated by this set of
rotations, all internal atomic distances
were computed. A confirmation for which
any distance less than the sum of the van
der Waals radii of the interacting species
was not considered. All the generated
conformers with minimum and maximum
torsion values were selected in the range
of-180.00 to 180.00, and MMFF force
field was selected for optimization of
generated conformers. The optimized
conformers were docked using the grid
batch docking method. The interaction
between synthesized compounds and DNA
gyrase pocket was recorded.
General procedure of synthesis
Synthesis of 6-substituted-2-
aminobenzothiazoles (B 1-5)
To substituted aniline (0.078 mol) taken
in a 250 ml round bottom flask,
ammonium thiocyanate (0.156 mol) and
100 ml acetic acid was added. Bromine
solution (0.02 mol) in acetic acid was
added to the reaction mixture till an
orange-yellow color appeared. The slurry
was kept overnight (20 h), the precipitate
was dissolved in water (200 ml), filtered to
remove any undissolved matter and was
basified with concentrated ammonia
solution. The precipitate obtained was
filtered, washed with water, dried and
recrystallized using ethanol: water (80:20)
mixture.13
Synthesis of 6-substituted-2-hydrazino
benzothiazole (BH 1-5)
Concentrated hydrochloric acid (1 ml)
was added dropwise with stirring to
hydrazine hydrate (0.12 mol) at 5-6 °C
followed by ethylene glycol (30 ml).
Thereafter 2-amino substituted
benzothiazole (20 mmol) was added in
portions, and the resultant mixture was
irradiated in microwave at power level 7
for 1 h. The reaction progress was
monitored by TLC using toluene: ethyl
acetate (75:25) as mobile phase. The
reaction mixture was cooled at room
temperature and was washed with cold
water to obtain the product. The resulting
crude was recrystallized from ethanol to
obtain the crystalline product 14
General Procedure for Synthesis of 6-
Substituted 2-(3-substituted 5-methyl
1H-pyrazol-1yl) benzothiazole (F1-10)
0.005mol of Substituted 2-hydrazino
benzothiazole (H1-5), ethyl acetoacetate or
acetyl acetone (0.001 mol) was placed in
3
 Design, Synthesis, Docking Studies And Biological Evaluation ……. Smita Pawar et al

two necked RBF and 10 ml of ethanol was TLC for completion of reaction. The
added to it. The reaction mixture was reaction mixture was cooled at room
irradiated in microwave for 10 min. at temperature to obtain the product.15
level of 5 and periodically monitored by

Fig. 1: Scheme of synthesis

NH2 N
NH4SCN NH2
Br2 in glacial acetic acid
R (00)stirring 24 hrs S
R
4-Substituted aniline
6-Substituted 2-amino benzothiazole
B(1-5)

NH2NH2 ethylene glycol

Con. HCl (5-100C) stirring

N
NH NH2

R S

6-Substituted 2-hydrazino benzothiazole

H(1-5)

ethanol Acetyl acetone/

Ethyl aceto acetate
reflux

1 R1= OC2H5, CH3

N N R R= 6-Cl, 6-OCH3,6-CH3,
N 6-NO2,6-H

S
R
CH3
6-Substituted 2-(3-substituted,5-methyl1H-pyrazol-1-yl)benzo[d]thiazole
F(1-10)

RESULTS AND DISCUSSION substituted 2-hydrazino benzothiazole

The compounds B(1-5) were prepared as (H1-5) with acetyl acetone or ethyl
per reported method from para-substituted acetoacetate in presence of ethanol. The
anilines by stirring with ammonium synthesized structures were confirmed by
thiocyanate and bromine in acetic acid. spectral analysis by IR, 1HNMR and were
The reaction mainly involves formation of found consistent with the spectral data. IR
intermediate phenylthiourea and spectra of F (1-10) revealed characteristic
cyclisation of which affords 6-substituted aromatic CH stretch between 3047-3120
2-amino benzothiazole. The target cm-1. The C=N in benzothiazole is seen at
compounds F (1-10) were synthesized by 1519-1600 cm-1.The absence of NH-NH2
the route indicated in fig. 1. The stretch at 3243-3317 cm-1 in the IR
compounds were prepared by refluxing spectrum also confirms the formation of 6-
4
 Design, Synthesis, Docking Studies And Biological Evaluation ……. Smita Pawar et al

Substituted 2-(3-substituted 5-methyl 1H The compound F-3 with chloro

pyrazol-1-yl) benzo[d]thiazole.
In the 1H NMR spectrum, a broad singlet
at 9-12 ppm is seen for hydrazine protons.
The aromatic protons were seen as
multiplet signals at 7.01-8.37 ppm. The
methoxy protons were seen downfield due
to the presence of oxygen and seen as a
singlet at 2.30 ppm and methyl protons as
a singlet at 2.39 ppm.
Antimicrobial activity
The minimum inhibitory concentration of
F (1-10) compounds was determined using
a double dilution method. A zone of
inhibition was determined using the cup
plate method using ciprofloxacin and
fluconazole as standard drugs for
antibacterial and antifungal activity.
Chloro substitution at 6th position of
benzothiazole found good for antibacterial
as well as antifungal activity. The order of
activity of substituents at 6th position of
benzothiazole was found to be
Cl>NO2>OCH3>H>CH3
substitution was found active against all
microbes at 12.5 and 25 µg/ml MIC. Also
compound F-8 was found to be active
against all strains at 25µg/ml MIC. It was
evident from the results of the zone of
inhibition that compound F-3 and
compound A-3 holds potential
antibacterial activity.
The zone of inhibition was determined
using the cup plate method. The data was
treated statistically. It is expressed as
mean±SEM. Data analysed by two-way
ANOVA followed by Dunnet test. All test
groups are compared with the control
groups. Variation in observations are
found statistically non-significant
therefore, the zone of inhibition shown by
synthesized compound is comparable to
control ciprofloxacin and fluconazole.
From the results it can be said that the
compound with chloro group substitution
holds antibacterial and antifungal potential
comparable to standard drugs.

Table 1: Data for 6-Substituted 2-(3-substituted 5-methyl 1H pyrazol-1-yl) benzo[d]

thiazole.(F1-10).

Compound R R1 IR NMR %
(ppm) yield
F1 OCH3 CH3 3132(ArC-H),2931(C- 6.03(s,1H,CH),3.88(s,3H,CH3),2.75(s,3H,C 68
H),1590(C=N),1234(C- H3),2.30(s,3H,OCH3),7.73(d,1H,Ar-
N),810(C-S),1011(C- H),7.01(d,1H,Ar-H),7.26(s,1H,Ar-H).
O),1543(C=C)
F2 CH3 CH3 3018(ArC-H),2924(C- 6.03(s,1H,CH),2.76(s,3H,CH3),2.46(s,3H,C 60
H),1524(C=N),1280(C- H3),2.30(s,3H,CH3),7.72(d,1H,Ar-
N),688(C-S),1527(C=C) H),7.22(d,1H,Ar-H),7.60(s,1H,Ar-H)
F3 Cl CH3 3117(Ar C-H), 2947(C- 6.05(s,1H,CH),2.30(s,3H,CH3),2.75(s,3H,C 67
H),1600(C=N),1134(C- H3),7.74(s,1H,Ar-H),7.77(d,1H,Ar-
N),810(C- H)7.37(d,1H,Ar-H)
S),1573(C=C),771(C-Cl)
F4 NO2 CH3 3110(Ar C-H), 2931(C- 6.10(s,1H,CH),2.32(s,3H,CH3),2.78(s,3H,C 70
H),1751(C=N),1141(C- H3),8.75(s,1H,Ar-H),7.90(d,1H,Ar-
N),783(C- H),8.31(d,1H,Ar-H)

5
 Design, Synthesis, Docking Studies And Biological Evaluation ……. Smita Pawar et al

S),1635(C=C),1334(N=O)
F5 H CH3 3055(Ar C-H), 2924(C- 6.03(s,1H,CH),2.30(s,3H,CH3),2.77(s,3 52
H),1580(C=N),1141(C- H,CH3),7.81-7.87(m,2H,Ar-H),7.25-
N),783(C-S),1573(C=C) 7.40(m,2H,Ar-H)
F6 OCH3 OC2H5 3009(Ar C-H),2901(C- 6.20(s,1H,CH),3.71(q,2H,CH2),1.32(t,3 59
H),1650(C=N),1211(C- H,CH3),2.46(s,3H,CH3)3.73(s,3H,OCH3
N),1101(C-O),758(C- ),7.37-7.39(m,2H,Ar-H),7.84(d,1H,Ar-
S),1526(C=C) H),8.04(d,1H,Ar-H)
F7 CH3 OC2H5 303(Ar C-H), 2978 (C- 6.00(s,1H,CH), 66
H),1750(C=N),1180(C- 3.26(q,2H,CH2),1.25(t,3H,CH3),2.46(s,3
N),1095(C-O),758(C- H,CH3)2.75(s,3H,CH3), 7.34-
S),1651(C=C) 7.41(m,2H,Ar-H),7.84(d,1H,Ar-
H),8.00(d,1H,Ar-H)
F8 Cl OC2H5 3132(Ar C-H), 2931(C- 5.99(s,1H,CH),3.71(q,2H,CH2),1.21(t,3 68
H),1610(C=N),1257(C- H,CH3),2.42(s,3H,CH3),7.37-
O),817(C- 7.39(m,2H,Ar-H),7.70(d,1H,Ar-
S),1558(C=C),710(C-Cl) H),8.10(d,1H,Ar-H)
F9 NO2 OC2H5 3309(Ar C-H),2924(C- 6.12(s,1H,CH),3.71(q,2H,CH2), 70
H),1745(C=N),1280(C- 1.30(t,3H,CH3),2.42(s,3H,CH3),7.37-
N),1128(C- 7.39(m,2H,Ar-H),7.70(d,1H,Ar-H),
O),748(CS)1550(C=C),145 8.10(d,1H,Ar-H)
0(N=O),
1327(N-O)
F10 H OC2H5 3124(Ar C-H), 2978(C- 5.94(s,1H,CH),3.71(q,2H,CH2),1.22(t,3 60
H),1745(C=N),1435(C- H,CH3),2.46(s,3H,CH3),7.37-
N),756(C- 7.39(m,2H,Ar-H),7.84(d,1H,Ar-
S),1527(C=C),1188(C-O) H),8.04(d,1H,Ar-H)

Table 2: Minimum inhibitory concentration (MIC) of 6-Substituted 2-(3-substituted 5-

methyl 1H pyrazol-1-yl) benzo[d] thiazole. (F1-10)

Compound MIC µg/ml

S. aureus B. subtilis E. coli P.aeruginosa A. niger C. albicans

F1 50 12.5 50 25 25 50
F2 50 25 50 50 25 50
F3 25 12.5 25 6.5 12.5 25
F4 50 25 50 12.5 25 50
F5 50 25 50 25 25 25
F6 25 50 25 50 25 50
F7 50 25 50 50 50 50
F8 25 25 25 12.5 12.5 25
F9 50 50 50 25 25 50
F10 50 50 50 25 25 50

6
 Design, Synthesis, Docking Studies And Biological Evaluation ……. Smita Pawar et al

Docking
To predict the probable interactions of The active site (cavity no 1) was defined to
newly synthesized compounds with the include residues within 10.0 A ° radius of
active site of DNA gyrase enzyme, any of the interaction. The docking
docking studies were carried out using procedure was validated by docking the
MDS V-life 3.5 software. The dock score, pyrazolthiazole extracted from PDB active
hydrophobic interactions, Van der Waal pocket. The molecular docking results
interactions and hydrogen bonds formed revealed a docking score of-4.8kcal/mol
with surrounding amino acids were used to for pyrazolthiazole, and it forms a single
predict the binding modes, binding hydrogen bond with Ser-55. The
affinities and orientation of docked compound F-3 is the most active
compounds in the active sites of DNA compound as antibacterial whichpossess
gyrase enzyme. dock score of -4.84 kcal/mol

Table 3: Dock score and binding interactions of newly synthesized compounds F (1-10)

Compound Dock score (kcal/mol)

F1 -4.37
F2 -4.63
F3 -4.84
F4 -4.71
F5 -4.68
F6 -4.16
F7 -4.37
F8 -4.52
F9 -4.40
F10 -4.58
Reference -4.35

Z o n e o f in h ib it io n o f t e s t c o m p o u n d s

50

NS
NS NS
NS C ip r o f lo x a c in
40
F1
z o n e o f in h ib itio n (m m )

F2
30 F3

F4

F5
20
F6

F7

10 F8

F9

F10
0
li
s

a
s
li

s
u
ti

o
c
re
b

in
.
u

E
u

g
.a
.s

ru
S
B

e
.a
P

S tr a in o f m ic r o o r g a n is m

Fig:2 Data expressed as mean±SEM. Data analyzed by two-way ANOVA followed by Dunnet test.
All test groups are compared with the control group, Ciprofloxacin

7
 Design, Synthesis, Docking Studies And Biological Evaluation ……. Smita Pawar et al

Z o n e o f in h ib it io n o f t e s t c o m p o u n d s in f u n g i

40
F lu c a n a z o le
N S N S
F1

z o n e o f in h ib itio n (m m ) 30 F2

F3

F4

20 F5

F6

F7
10 F8

F9

F10
0
r

s
e

n
ig

a
ic
.n

lb
A

.a
C
S p e c ie s

Fig:3 Data expressed as mean±SEM. Data analyzed by two-way ANOVA followed by Dunnet test.
All test groups are compared with the control group, Fluconazole.

CONCLUSION CONFLICT OF INTERESTS

The number of substituted benzothiazole Declared none
fused with pyrazole moieties was
synthesized and screened for antibacterial REFERENCES
and antifungal activity. The antimicrobial 1. Morens DM, Folkers GK, Fauci
activities for the synthesized compounds AS. The challenge of emerging and
(F1-10) have been shown in table 2, fig. 2 re-emerging infectious diseases.
and fig. 3 Ciprofloxacin was used as a Nature, 2004, 430(6996), 242–249
standard for antibacterial activity. 2. Brown, E. D., Wright, G. D.
Similarly, for antifungal activity Antibacterial drug discovery in the
fluconazole was used as standard. All the resistance era.
newly synthesized compounds showed Nature,2016;529:336–343
moderate to good potency against different 3. Oren I, Yalcin I, Senar E¸ Ucarturk
bacterial strains. Out of which compound N. Synthesis and structureactivity
F3and F-8 showed good antibacterial and relationships of new antimicrobial
antifungal activity. active multisubstitutedbenzoxazole
derivatives. European Journal of
ACKNOWLEDGMENT Medicinal Chemistry.2004;34:291–
The authors wish to thank Principal, S. G. 8.
R. S College of Pharmacy, Saswad Pune 4. Geofrey W, Bradshaw TD, Patrizia
for providing required facilities to carry Diana, Angela S, Dong Fang Shi,
out this research work. Andrew D, et al.
Antitumourbenzothiazoles. Part10:
AUTHORS CONTRIBUTIONS the synthesis and antitumor activity
All the authors have contributed equally of benzothiazole substituted quinol

8
 Design, Synthesis, Docking Studies And Biological Evaluation ……. Smita Pawar et al
derivatives. Bioorg Med Chem Lett
2000;1:513-5.
5. Delmas F, Avellaneda A, Giorgio
C, Robin M, Clercq E, David P, et
al. Synthesis and antileishmanial
activity of (1,3- benzothiazol-2-yl)
amino-9-(10H)-acridinone
derivatives. European Journal of
Medicinal Chemistry.2004;1:685-
90.
6. Bujdakovi H, Mfikovfi M.
Antifungal activity of a new
benzothiazole derivative against
Candida in vitro and in vivo. Inter J
Antimicrobial Agents 1994;4:303-
8.
7. Liu, X.H., Cui, P., Song, B.A.,
Bhadury, P.S., Zhu, H.L. and
Wang, S.F. Synthesis, Structure
and Antibacterial Activity of Novel
1-(5-substituted-3-substituted-4,5-
dihydropyrazol-1-yl)ethanone
Oxime Ester Derivatives.
Bioorganic & Medicinal
Chemistry,2008,16,4075-4082.
8. Bers,T.; Angehrn,P.; Nder, H.;
Herzig, S.; Kulhanek,
J.Design,synthesis,and structure-
activity relationship studies of ATP
analogues as DNA gyrase
inhibitors. Bioorganic & Medicinal
Chemistry Letters,2000,10,821-
826.
9. Oblak, Simona M, Roman GG,
Filipic J, Tomaz SO. In silico
fragment-based discovery of
indolin-2-one analogues as potent
DNA gyrase inhibitors. Bioorganic
& Medicinal Chemistry Letters,
2005;15:5207.
10. Singh, H., Sharma ,S. ,Gautam ,C.
American Eurasian Journal of
Scientific Research.2009,1408-
1414.
View publication stats
11. Rashid,N.;Peter,G.;Muhammad,A.;
Hussain,R.European Journal of
Medicinal
Chemistry.2010,45,1323-1331.
12. Chryssanthou,E.;Estrella,M.;Denni
ng,D,Donelly,J.;Dupont,B.Clinical
Microbiology and
Infection.2003,9,1-8.
13. Rana A, Siddiqui N, Khan A,
Haque S, Bhat M. N-{[(6-
Substituted-1,3-benzothiazole-2-yl)
amino]carbonothioyl}- 2/4-
substituted benzamides: Synthesis
and pharmacological evaluation.
European Journal of Medicinal
Chemistry. European Journal of
Medicinal Chemistry2008;1:1114-
22.
14. Basavaraja K, Somasekhar B,
Shivakumar B. Synthesis of 2-[(1-
phenyl) (aryl) azo]
methyleneimino-6-
chloro/fluorobenzothiazoles and
their antibacterial activity. Inter J
Pharm Tech Res 2010;2:1139-43
15. Goud,A., Chandra, N., Nargunda,
L.V.G., Shachindra, N., Chidvila,
V., Ramya, S., Balakrishna, V.
Scholers Research Library Der
Pharma Chemica. 2012,4,1408-
1414.