Synthesis and evaluation of some benzothiazole derivatives as antidiabetic agents

Article abstract of DOI:10.22159/ijpps.2017v9i2.14359

Objective: The objective of the present research investigation involves synthesis and biological evaluation of antidiabetic activity of benzothiazole derivatives. Methods: A novel series of benzothiazole derivatives 7(a-l) were synthesised and synthesised compounds were characterised for different physical and chemical properties like molecular formula, molecular weight, melting point, percentage yield, Rf value, IR,¹HNMR,¹³CNMR and mass spectroscopy. The newly synthesised benzothiazole derivatives were subsequently assayed in vivo to investigate their hypoglycemic activity by the alloxan-induced diabetic model in rats. Results: All the synthesised derivatives showed significant biological efficacy. The compound 7d at 350 mg/kg exerted maximum glucose lowering effects whereas 7c showed minimum glucose lowering effects. All the compounds were effective, and experimental results were statistically significant at p<0.01 and p<0.05 level. Conclusion: From the results, it is clear that compound 7d demonstrated potent anti-diabetic activity and would be of better use in drug development to combat the metabolic disorder in future.

Full text of DOI:10.22159/ijpps.2017v9i2.14359

International Journal of Pharmacy and Pharmaceutical Sciences
ISSN- 0975-1491
Vol 9, Issue 2, 2017
Original Article
SYNTHESIS AND EVALUATION OF SOME BENZOTHIAZOLE DERIVATIVES AS ANTIDIABETIC
AGENTS
SUNIL KUMARb*, D. S. RATHOREa, GOPAL GARGa, KAPIL KHATRIb, RAHUL SAXENAb, SANJEEV K. SAHUb
aNIMS Institute of Pharmacy, NIMS University, Jaipur (Rajasthan) India, bRavishankar College of Pharmacy, Bhopal (M. P.) India
Email: yagnikvns@gmail.com
Received: 28 Jul 2016 Revised and Accepted: 07 Dec 2016
ABSTRACT
Objective: The objective of the present research investigation involves synthesis and biological evaluation of antidiabetic activity of benzothiazole
derivatives.
Methods: A novel series of benzothiazole derivatives 7(a-l) were synthesised and synthesised compounds were characterised for different physical
and chemical properties like molecular formula, molecular weight, melting point, percentage yield, Rf value, IR, 1HNMR, 13CNMR and mass
spectroscopy. The newly synthesised benzothiazole derivatives were subsequently assayed in vivo to investigate their hypoglycemic activity by the
alloxan-induced diabetic model in rats.
Results: All the synthesised derivatives showed significant biological efficacy. The compound 7d at 350 mg/kg exerted maximum glucose lowering
effects whereas 7c showed minimum glucose lowering effects. All the compounds were effective, and experimental results were statistically
significant at p<0.01 and p<0.05 level.
Conclusion: From the results, it is clear that compound 7d demonstrated potent anti-diabetic activity and would be of better use in drug
development to combat the metabolic disorder in future.
Keywords: Diabetes, Substituted benzthiazole derivatives, Thiazolidinedione, Hypoglycemic activity
© 2017 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4. 0/)
DOI: http://dx.doi.org/10.22159/ijpps.2017v9i2.14359
INTRODUCTION
Benzothiazole derivatives containing benzimidazole and
imidazoline ring have diverse chemical reactivity along with a
broad spectrum of biological activity [10]. In view of this
literature, it was of significant interest to synthesise the benzo-
thiazole derivatives with an aim to obtain potent biologically
active and safe anti-diabetic agents.
Diabetes mellitus is an endocrinological and metabolic disorder with
an increasing global prevalence and incidence. High blood glucose
levels are symptomatic of diabetes mellitus as a consequence of
inadequate pancreatic insulin secretion or poor insulin-directed
mobilisation of glucose by target cells [1]. The world health
organisation (WHO) estimates that more than 220 million people
worldwide have diabetes and this number is likely to double by
2030 (WHO, 2009). Several drugs such as sulfonylurea and
biguanides are presently available to reduce hyperglycemia in
diabetes mellitus.
MATERIALS AND METHODS
All the chemicals were of synthetic grade and commercially
procured from hi media chemicals, Mumbai (Maharashtra) INDIA.
ERBA diagnostic kit was used for the determination of glucose.
Melting points were determined on a tempo capillary melting point
apparatus in open capillary tube. UV-visible spectrophotometric
determination was carried on systronics 2203. All FTIR spectra were
recorded (νmax in cm-1) on bruker tensor 27 FT-IR spectrometer.
1H-NMR (proton nuclear magnetic resonance) spectrum were
These drugs have a number of side effects and thus searching for a
new class of compounds is crucial to overcoming these problems.
Heterocyclic compounds are the mainstay of antidiabetic therapy for
many years [2]. Also, certain hypoglycemic plants may also be useful
to develop evidence-based alternative medicine to cure different
kinds of diabetes in man and animals [3].
recorded at 300 MHz, after dissolving in
a suitable solvent
(DMSO,CDCl3 or D2O) on bruker avance II 400 MHz, USA FT-NMR
spectrometer using tetramethylsilane as internal standard and
chemical shifts (δ) are reported in parts per million (ppm). 13C NMR
was also recorded on bruker avance II FT-NMR spectrometer at a
frequency of 100 MHz. The spin multiplicities are indicated by
symbols, s (singlet), d (doublet), t (triplet), q (quartet), m (multiple)
and br (broad). Mass spectra were recorded on Waters UPLC-TQD
mass spectrometer using electrospray ionisation (ESI) technique.
Benzothiazole is a weak heterocyclic base, having varied biological
activities and of great scientific interest nowadays. Benzothiazoles
are fused membered rings, which contain the heterocycles bearing
thiazole. Sulphur and nitrogen atoms constitute the core structure of
thiazole and many pharmacologically and biologically active
compounds [4]. Benzothiazole ring system is present in various
marine and terrestrial natural compounds, which have useful
biological activities [5].
The purity of the compounds was ascertained by thin layer
chromatography (TLC) and elemental analysis. Plates for TLC were
prepared with silica gel G and activated at 110 °C for 30 min. Iodine
vapours were used to develop the TLC plates. Elemental analyses
were performed on a vario EL-III analyser.
The benzthiazole derivatives have demonstrated efficiency in
biological fields such as antitumor, antitubercular, antimalarial,
anticonvulsant,
antifungal, a topical carbonic anhydrase inhibitor and an anti-
hypoxic. They are broadly found in bioorganic and medicinal
chemistry with applications in drug discovery and development for
the treatment of diabetes [6, 7]. Due to it's potent and significant
biological activities, it has great pharmaceutical importance [8, 9].
anthelmintic,
analgesic,
anti-inflammatory,
General method of synthesis for benzthiazole derivatives
All the compounds were synthesised by using a synthetic route
given in scheme as follows:

Sunil et al.
Int J Pharm Pharm Sci, Vol 9, Issue 2, 60-68
Table 1: Benzothiazole derivatives with different substitutions
S. No.
1.
Compound code
R1
R2
H
R3
C6H5-
7a
7b
7c
7d
7e
7f
7g
7h
7i
CH3
CH3
CH3
CH3
NO2
NO2
NO2
NO2
H
2.
H
pOHC6H4-
pOCH3C6H4-
m NO2C6H4-
C6H5-
pOHC6H4-
pOCH3C6H4-
m NO2C6H4-
C6H5-
3.
H
4.
H
5.
H
6.
H
7.
H
H
NO2
NO2
NO2
NO2
8.
9.
10.
11.
12.
7j
7k
7l
H
pOHC6H4-
pOCH3C6H4-
m NO2C6H4-
H
H
R2
H2N
R1
Conc. HCl
R1
NH2HCl
Aniline
R2
2
1
CS2, KOH, S
EtOH, H2O
Reflux
R2
N
S
R2
N
S
O
EtOH
SH
ClCH2COOC2H5
R1
S
4
R1
O
3
EtOH , NH2NH2.H2O
R2
H2N
N
S
S
NH
O
R3-CHO
CHR3
R1
R2
R1
N
N
S
5
S
NH
6
O
R1 = H, CH3, NO2
R2 = H, NO2
SHCH2COOH, DMF, ZnCl2
O
R3 = -C6H5,
p-C6H5OH,
p-C6H5OCH3,
m-C6H5NO2
R1
H
N
N
S
N
S
S
O
R2
7a- l
R3
Fig. 1: Scheme of synthesis for benzothiazole derivatives
Synthesis of substituted aniline hydrochloride salt [Compound 2]
presence of sulphur (5 ml) and absolute ethanol (30 ml) was heated
under reflux for 2 h at 280-285 °C and 600-700 psi pressure. The
reaction mixture was cooled, filtered and the filtrate was acidified
with a dilute hydrochloric acid, the product thus obtained was
collected and recrystallized from ethanol [11].
Aniline (0.1 mol) was taken in a round bottom flask and to it a
mixture of HCl (9 ml) and water (25 ml) was added. Then the
solution was heated for about 30 min and then cooled at room
temp. Further, ammonium thiocyanate (0.1 mol) was added to the
reaction mixture, refluxed for 4 h and was cooled. The precipitate
thus obtained was filtered, washed with water, dried and
crystallised from ethanol.
Synthesis of substituted ethyl 2-(benzo[d]thiazol-2-ylthio)
acetate [Compound 4]
2-mercaptobenzothiazole (0.2 mol) and ethyl chloroacetate (0.02
mol) in dry acetone in the presence of K2CO3 (20g) was refluxed for
10 h and the reaction mixture was poured into ice and neutralised
with dil. HCl, the solid thus obtained was washed several times with
water and recrystallized from chloroform.
Synthesis of substituted benzo[d]thiazole-2-thiol [Compound 3]
A mixture of compound 1 (0.0025 mol), potassium hydroxide (0.75
gm) in water (6 ml) and carbon disulphide (1.6 g, 0.01 mol) in
61

Sunil et al.
Int J Pharm Pharm Sci, Vol 9, Issue 2, 60-68
Synthesis of substituted 2-(benzo[d]thiazol-2-ylthio) aceto-
hydrazide [Compound 5]
5% (w/v) dextrose solution in feeding bottles for next 24 h in their
cages to to prevent hypoglycaemia. The animals showing blood
glucose range of 200-400 mg dL-1 were used for the experiment
Into
a clean, dry 100 ml round bottomed flask, the ethyl-2-
and the hyperglycemia was confirmed after 72
h of alloxan
benzothiazole carboxylate (0.01 mol) was dissolved in ethanol (60
ml). The hydrazine hydrate (0.02 mol) (99%) was added drop by
drop with constant stirring and the content were refluxed for 8 h
and thus cooled to room temperature.
monohydrate administration (i. p.). The animals were also
observed for consistent hyperglycaemia (fasting blood glucose)
between 200-400 mg/dl up to 14 d.
Experimental design
Synthesis of substituted 2-(benzo[d]thiazol-2-ylthio)-N'-methyl-
eneacetohydrazide [Compound 6]
Animals were divided into fourteen groups of 6 animals in each (n=6).
Group 1 diabetic animals received 1 ml of 0.5% carboxymethyl
cellulose as a control group; Group 2 diabetic animals received
Glibenclamide 20 mg/kg as a standard group; Groups (3-14) diabetic
animals received compounds 7a-7l in a single dose of 350 mg/kg body
weight p. o. respectively for 14 d continuously.
A
mixture of compound 5 (1 g, 0.0034 mol) and different
benzaldehydes (0.0034 mol) were taken with absolute ethanol (20
ml) and was refluxed for 3 h. The solvent was evaporated and the
residue was recrystallized from ethanol [12].
Synthesis of benzthiazole derivatives [Compound 7a-l]
Blood glucose measurement
A mixture of the previous compound (0.01 mol) and mercapto acetic
acid (0.012 mol) in DMF (25 ml) containing a pinch of anhydrous
ZnCl2 was refluxed for 8 h. The reaction mixture was then cooled
and poured into ice-cold water. The resulting solid was filtered,
washed several times with water and then crystallised from DMF
[13].
Blood glucose level was monitored by a tail dipping method. The
blood sample was dropped on the dextrostrix reagent pad. The strip
was inserted into microprocessor digital blood glucometer, and
reading was noted. The blood glucose level was monitored at 0 h, 3h,
7h, 10 h respectively.
Statistical analysis
Determination of physical properties of synthesised derivatives
The values were expressed as mean±SEM Data were analysed using
One-way ANOVA followed by Tukey-Kramer test. The values were
considered to be significant at p<0.05 and p<0.01 level.
The physical properties were determined for all the synthesised
derivatives that include molecular formula, molecular weight,
melting point, percentage yield and Rf value.
RESULTS AND DISCUSSION
Pharmacological evaluation of synthesised derivatives
Determination of acute toxicity (OECD 425, 2008) [14]
All the benzthiazole derivatives 7(a-l) were synthesised by the given
scheme and reaction process was monitored by thin layer
chromatography method using silica gel-G stationary phase, ethyl
acetate: ethanol (2:3) as mobile phase, and detecting the spots with
iodine vapours. All the constant physical data were characterised for
all the synthesised derivatives that are given in the synthesised
derivatives were also confirmed by FTIR, 1H NMR, C13NMR and mass
spectroscopy method. The FTIR spectrums demonstrated the
significant peaks at 3270-3260 cm-1(N-H strech.), 1720-1710 cm-
1(cyclic C=O strech.), 1660 cm-1(amide C=O stretch.), 1320-1310 cm-
1(C-N Strech), 695-685 cm-1(C-S stretch) cm-1.
The acute toxicity of synthesised benzothiazole derivatives was
determined by using female albino rats (200–250 g) which were
maintained under the standard conditions. The acclimatised animals
(n= 6) were kept fasting with water ad libitum for 12 h prior to the
experiment. The animals were administered with single dose of test
compound at a dose of 2000 mg/kg and observed for their mortality
during 14 d period for toxicity study. The doses were increased up
to 1000 mg/kg and rats were observed up to 02 w for their
behavioural, economical and neurological profiles except for slight
depression in their activity. No such signs, symptoms and mortality
were observed even after 14 d. Hence the LD50 cut off the value of
the test compounds was fixed at 350 mg/kg and the same dose was
considered for evaluation of the antidiabetic activity. All the animal
experiments were conducted by the approval of Institutional Animal
Ethics Committee (Approval No. SBRL/IAEC/July2015/12), Sapience
Bioanalytical Laboratory Bhopal, Madhya Pradesh, India
The different substitutions on phenyl ring were confirmed through FTIR
spectrum peaks at 3480-3460 cm-1(O-H stretch.) for hydroxyl group,
1250 (asym. C-O strech.) and 1038 (sym. C-O stretch.) for methoxy
group, 1385-90 (sym. CH3 bending) and 1330-40 (sym NO2 bending) for
nitro group substitution. The proton NMR spectrums also confirmed the
different substitutions on phenyl as well as benzothiazole ring distinct
due to change in the environment of protons. Similarly, the environment
surrounding carbon atoms were also changed which were confirmed
through the C13NMR. The mass spectroscopy studies confirmed the
molecular weight of derivatives through molecular ion peak on the mass
spectrum (i.e. peak at highest m/e).
Assessments of anti-diabetic activity in alloxan-induced
diabetic rats [15]
Induction of experimental diabetes by alloxan monohydrate
The fresh solution of alloxan monohydrate in normal saline was
administered p. o. into fasted rats at a dose of 120 mg/kg body
weight [16, 17]. After alloxan administration (i. p.), rats were given
Table 2: Physical constant data of synthesised derivatives
Properties
Molecular formula
Molecular weight
Melting point in °C
% Yield
Retention factor
Code of derivatives
7a
7b
7c
7d
7e
7f
7g
7h
7i
C19H17N3O2S3
C19H17N3O3S3
C20H19N3O3S3
C19H16N4O4S3
C18H14N4O4S3
C18H14N4O5S3
C19H16N4O5S3
C18H13N5O6S3
C18H14N4O4S3
C18H14N4O5S3
C19H16N4O5S3
C18H13N5O6S3
415.55
431.55
445.58
460.55
446.52
462.52
476.55
491.52
446.52
462,52
476.55
491.52
168-170
188-189
210-212
276-278
165-167
184-186
207-209
273-275
161-163
179-181
202-204
269-271
62.5
68.7
72.3
76.2
59.5
63.2
69.1
74.8
56.8
61.3
67.7
71.9
0.58
0.62
0.64
0.72
0.63
0.68
0.71
0.78
0.61
0.69
0.70
0.77
7j
7k
7l
62

Sunil et al.
Int J Pharm Pharm Sci, Vol 9, Issue 2, 60-68
(A) 2-(5-methylbenzo[d]thiazol-2-ylthio)-N-(4-oxo-2-phenyl-
thiazolidin-3-yl)acetamide [compound 7a]
phenyl linkage), 41.2 (-S-CH2-CONH-), 36.4 (thiazole ring carbon at-
C=O linkage), 24.5 (methyl carbon at benzthiazole ring).
Yield: 62.5 %; M. P. 168-170 °C; Anal. Cal. for C19H17N3O2S3: C,
54.92; H, 4.12; N, 10.11; O, 7.70; S, 23.15%; found: C, 54.92; H, 4.14;
N, 10.06; O, 7.72; S, 23.13%;
Mass spectroscopy
Molecular ion peak demonstrated on mass spectrum and reported
m/e (ESI): 432 (M+).
FT-IR spectroscopy
(C) N-(2-(4-methoxyphenyl)-4-oxothiazolidin-3-yl)-2-(5-
methylbenzo[d]thiazol-2-ylthio) acetamide [compound 7c]
FT-IR (νmax): 3265 (N-H strech.), 3030 (aromatic C-H strech.),
2960(asym. aliphatic C-H strech.), 2858 (sym. aliphatic C-H
strech.), 1670-2000 (overtone for substitution on aromatic ring),
1710 (cyclic C=O strech.), 1660 (amide C=O stretch.), 1598
(phenyl ring stretch.), 1578 (N-H bending), 1510 (phenyl C-H out
of plane bending), 1465 (CH2 bending), 1456 (asym CH3
bending), 1389 (sym. CH3 bending), 1315 (C-N Strech), 690 (C-S
Yield: 73.3 %; M. P. 210-212 °C; Anal. Cal. for C20H19N3O3S3: C,
53.91; H, 4.30; N, 9.43; O, 10.77; S, 21.59 %; found: C, 53.93; H, 4.32;
N, 9.44; O, 10.71; S, 21.60%.
FT-IR spectroscopy
stretch) cm-1
.
FT-IR (νmax): 3266 (N-H strech.), 3035 (aromatic C-H strech.),
2969(asym. aliphatic C-H strech.), 2862 (sym. aliphatic C-H strech.),
1670-2000 (overtone for substitution on aromatic ring), 1712
(cyclic C=O strech.), 1660 (amide C=O stretch.), 1599 (phenyl ring
stretch.), 1579 (N-H bending), 1515 (phenyl C-H out of plane
bending), 1464 (CH2 bending), 1455 (asym CH3 bending), 1387
(sym. CH3 bending), 1315 (C-N Strech), 1250 (asym. C-O strech.),
1038 (sym. C-O stretch.), 694 (C-S stretch) cm-1.
1H-NMR spectroscopy
1H-NMR (CDCl3) (δ, ppm): 7.94 (s,1H,-CONH-), 7.89-7.78 (m, 3H,
benzthiazole ring protons), 7.36-7.26 (m, 5H, phenyl ring protons),
5.92 (s, 1H, thiazole ring protons at phenyl linkage), 4.35 (s, 2H,-
SCH2-), 3.95-3.82 (s, 2H, thiazole ring protons), 2.33 (s, 3H, CH3 at
benzthiazole linkage).
1H-NMR spectroscopy
13C-NMR spectroscopy
1H-NMR (CDCl3) (δ, ppm): 7.94 (s,1H,-CONH-), 7.89-7.63 (m, 3H,
benzthiazole ring protons), 7.35-6.86 (m, 4H, phenyl ring protons),
5.91 (s, 1H, thiazole ring protons at phenyl linkage), 4.35 (s, 2H,-
SCH2-), 3.95-3.82 (s, 2H, thiazole ring protons), 2.34 (s, 3H, CH3 at
benzthiazole linkage).
13C-NMR (CDCl3) (δ, ppm): 170.3 (C=O, amide carbon), 168.6 (C=O
thiazole ring carbon), 164.2 (C=N bezthiazole ring carbon at sulfur
linkage), 150.5 (C-N benzthiazole ring carbon), 139.2 (phenyl ring
carbon at thiazole linkage), 134.2-135.0 (bezthiazole ring carbons at
sulfur and methyl linkage), 127.2-128.8 (phenyl ring carbons),
121.5-126.6 (benzthiazole ring carbons at proton linkage), 57.3
(thiazole ring carbon at phenyl linkage), 40.9 (-S-CH2-CONH-), 35.7
(thiazole ring carbon at-C=O linkage), 23.9 (methyl carbon at
benzthiazole ring)
13C-NMR spectroscopy
13C-NMR (CDCl3 ) (δ, ppm): 170.9 (C=O, amide carbon), 168.5
(C=O thiazole ring carbon), 163.8 (C=N bezthiazole ring carbon
at sulfur linkage), 151.9 (C-N benzthiazole ring carbon), 159.2
(phenyl ring carbon at methoxy linkage), 134.6-136.2
(bezthiazole ring carbons at sulfur and methyl linkage), 131.5
(phenyl ring carbon at thiazole linkage), 121.1-126.3
(benzthiazole ring carbons at proton linkage), 114.2-125.9
(phenyl ring carbons), 58.3 (thiazole ring carbon at phenyl
linkage), 41.9 (-S-CH2 -CONH-), 36.8 (thiazole ring carbon at-C=O
linkage), 24.3 (methyl carbon at benzthiazole ring).
Mass spectroscopy
Molecular ion peak demonstrated on mass spectrum and reported
m/e (ESI): 415 (M+).
(B) N-(2-(4-hydroxyphenyl)-4-oxothiazolidin-3-yl)-2-(5-
methylbenzo[d]thiazol-2-ylthio) acetamide [compound 7b]
Yield: 68.7 %; M. P. 188-189 °C; Anal. Cal. for C19H17N3O3S3: C,
52.88; H, 3.97; N, 9.74; O, 11.12; S, 22.29%; found: C, 52.91; H, 3.95;
N, 9.76; O, 11.14; S, 22.24%;
Mass spectroscopy
Molecular ion peak demonstrated on mass spectrum and reported
m/e (ESI): 446 (M+).
FT-IR spectroscopy
(D) 2-(5-methylbenzo[d]thiazol-2-ylthio)-N-(2-(3-nitrophenyl)-
4-oxothiazolidin-3-yl) acetamide [compound 7d]
FT-IR (νmax): 3465 (O-H stretch.), 3268 (N-H strech.), 3033
(aromatic C-H strech.), 2962(asym. aliphatic C-H strech.), 2861
(sym. aliphatic C-H strech.), 1670-2000 (overtone for substitution
on aromatic ring), 1714 (cyclic C=O strech.), 1662 (amide C=O
stretch.), 1603 (phenyl ring stretch.), 1580 (N-H bending), 1512
(phenyl C-H out of plane bending), 1466 (CH2 bending), 1458 (asym
CH3 bending), 1388 (sym. CH3 bending), 1317 (C-N Strech), 692 (C-S
stretch) cm-1.
Yield: 76.2 %; M. P. 276-278 °C; Anal. Cal. for C19H16N4O4S3: C,
49.55; H, 3.50; N, 12.17; O, 13.90; S, 20.89 %; found: C, 49.53; H,
3.48; N, 12.14; O, 13.95; S, 20.91 %.
FT-IR spectroscopy
FT-IR (νmax): 3258 (N-H strech.), 3038 (aromatic C-H strech.),
2972(asym. aliphatic C-H strech.), 2865 (sym. aliphatic C-H strech.),
1670-2000 (overtone for substitution on aromatic ring), 1714
(cyclic C=O strech.), 1658 (amide C=O stretch.), 1597 (phenyl ring
stretch.), 1575 (N-H bending), 1538 (asym. NO2 strech), 1516
(phenyl C-H out of plane bending), 1466 (CH2 bending), 1453 (asym
CH3 bending), 1389 (sym. CH3 bending), 1334 (sym NO2 bending),
1312 (C-N Strech), 696 (C-S stretch) cm-1. FT-IR image of the
synthesized compound is shown in fig. 2.
1H-NMR spectroscopy
1H-NMR (CDCl3) (δ, ppm): 7.94 (s,1H,-CONH-), 7.89-7.76 (m, 3H,
benzthiazole ring protons), 7.35-6.63 (m, 4H, phenyl ring protons),
5.91 (s, 1H, thiazole ring protons at phenyl linkage), 5.35(s,1H,-
C6H4-OH), 4.35 (s, 2H,-SCH2-), 3.95-3.83 (s, 2H, thiazole ring
protons), 2.34 (s, 3H, CH3 at benzthiazole linkage).
13C-NMR spectroscopy
1H-NMR spectroscopy
13C-NMR (CDCl3) (δ, ppm): 170.4 (C=O, amide carbon), 168.8 (C=O
thiazole ring carbon), 164.4 (C=N bezthiazole ring carbon at sulfur
linkage), 151.3 (C-N benzthiazole ring carbon), 156.9 (phenyl ring
carbon at hydroxyl linkage), 134.3-135.8 (bezthiazole ring carbons
at sulfur and methyl linkage), 131.8 (phenyl ring carbon at thiazole
linkage), 121.5-126.6 (benzthiazole ring carbons at proton linkage),
115.8-125.2 (phenyl ring carbons), 57.8 (thiazole ring carbon at
1H-NMR (CDCl3) (δ, ppm): 8.10 (s,1H,-CONH-), 8.06-7.87 (m, 4H,
phenyl ring protons), 7.81-7.33 (m, 3H, benzthiazole ring protons),
5.92 (s, 1H, thiazole ring protons at phenyl linkage), 4.35 (s, 2H,-
SCH2-), 3.95-3.83 (s, 2H, thiazole ring protons), 2.34 (s, 3H, CH3 at
benzthiazole linkage).1H-NMR image of the synthesized compound is
shown in fig. 3.
63

Sunil et al.
Int J Pharm Pharm Sci, Vol 9, Issue 2, 60-68
Fig. 2: FT-IR image of synthesised compound 7d
Fig. 3: 1H-NMR image of synthesised compound 7d
13C-NMR spectroscopy
C=O strech.), 1665 (amide C=O stretch.), 1602 (phenyl ring stretch.),
1581 (N-H bending), 1536 (asym. N=O strech), 1513 (phenyl C-H out
of plane bending), 1467 (CH2 bending), 1342 (sym. N=O strech),
1318 (C-N Strech), 687 (C-S stretch) cm-1.
13C-NMR (CDCl3) (δ, ppm): 171.2 (C=O, amide carbon), 167.9 (C=O
thiazole ring carbon), 164.2 (C=N bezthiazole ring carbon at sulfur
linkage), 152.3 (C-N benzthiazole ring carbon), 147.2 (phenyl ring
carbon at nitro linkage), 145.3 (phenyl ring carbon at thiazole
linkage), 134.3-135.5 (bezthiazole ring carbons at sulfur and methyl
linkage), 121.4-126.7 (benzthiazole ring carbons at proton linkage),
121.1-129.2 (phenyl ring carbons), 57.6 (thiazole ring carbon at
phenyl linkage), 40.5 (-S-CH2-CONH-), 35.9 (thiazole ring carbon at-
C=O linkage), 23.7 (methyl carbon at benzthiazole ring).
1H-NMR spectroscopy
1H-NMR (CDCl3) (δ, ppm): 8.66 (s,1H,-CONH-), 8.35-7.95 (m, 3H,
benzthiazole ring protons), 7.35-7.18 (m, 5H, phenyl ring protons),
5.92 (s, 1H, thiazole ring protons at phenyl linkage), 4.35 (s, 2H,-
SCH2-), 3.95-3.82 (s, 2H, thiazole ring protons).
13C-NMR spectroscopy
Mass spectroscopy
13C-NMR (CDCl3) (δ, ppm): 172.1 (C=O, amide carbon), 169.3 (C=O
thiazole ring carbon), 165.8 (C=N bezthiazole ring carbon at sulfur
linkage), 154.4 (C-N benzthiazole ring carbon), 140.1 (phenyl ring
carbon at thiazole linkage), 141.1-145.2 (bezthiazole ring carbons at
sulfur and nitro linkage), 126.8-129.3 (phenyl ring carbons), 117.1-
122.2 (benzthiazole ring carbons at proton linkage), 58.7 (thiazole
ring carbon at phenyl linkage), 41.6 (-S-CH2-CONH-), 37.1 (thiazole
ring carbon at-C=O linkage).
Molecular ion peak demonstrated on mass spectrum and reported
m/e (ESI): 461(M+).
(E) 2-(5-nitrobenzo[d]thiazol-2-ylthio)-N-(4-oxo-2-
phenylthiazolidin-3-yl)acetamide [compound 7e]
Yield: 59.5 %; M. P. 165-167 °C; Anal. Cal. for C18H14N4O4S3: C,
48.42; H, 3.16; N, 12.55; O, 14.33; S, 21.54%; found: C, 48.39; H, 3.13;
N, 12.59; O, 14.34; S, 21.55%.
Mass spectroscopy
FT-IR spectroscopy
Molecular ion peak demonstrated on mass spectrum and reported
m/e (ESI): 447 (M+).
FT-IR (νmax): 3263 (N-H strech.), 3032 (aromatic C-H strech.), 2964
(asym. aliphatic C-H strech.), 2862 (sym. aliphatic C-H strech.),
1670-2000 (overtone for substitution on aromatic ring), 1714(cyclic
(F) N-(2-(4-hydroxyphenyl)-4-oxothiazolidin-3-yl)-2-(5-
nitrobenzo[d]thiazol-2-ylthio) acetamide [compound 7f]
64

Sunil et al.
Int J Pharm Pharm Sci, Vol 9, Issue 2, 60-68
Yield: 63.2 %; M. P. 184-186 °C; Anal. Cal. for C18H14N4O5S3: C,
46.74; H, 3.05; N, 12.11; O, 17.30; S, 20.80%; found: C, 46.76; H, 3.08;
N, 12.06; O, 17.34; S, 20.76%.
Yield: 74.8 %; M. P. 273-275 °C; Anal. Cal. for C18H13N5O6S3: C,
43.98; H, 2.67; N, 14.25; O, 19.53; S, 19.57 %; found: C, 43.96; H,
2.65; N, 14.23; O, 19.56; S, 19.60%.
FT-IR spectroscopy
FT-IR spectroscopy
FT-IR (νmax): 3468 (O-H stretch.), 3274 (N-H strech.), 3038 (Aromatic
C-H strech.), 2969 (asym. aliphatic C-H strech.), 2867 (sym. aliphatic C-H
strech.), 1670-2000 (overtone for substitution on aromatic ring), 1716
(cyclic C=O strech.), 1665 (amide C=O stretch.), 1601 (phenyl ring
stretch.), 1578 (N-H bending), 1538 (asym. N=O strech), 1509 (phenyl C-
H out of plane bending), 1469(CH2 bending), 1342 (sym. N=O strech),
1319 (C-N Strech), 689 (C-S stretch) cm-1.
FT-IR (νmax): 3261 (N-H strech.), 3040 (aromatic C-H strech.), 2975
(asym. aliphatic C-H strech.), 2868 (sym. aliphatic C-H strech.),
1670-2000 (overtone for substitution on aromatic ring), 1716
(cyclic C=O strech.), 1661 (amide C=O stretch.), 1599 (phenyl ring
stretch.), 1577 (N-H bending), 1540 (asym. NO2 strech), 1514
(phenyl C-H out of plane bending), 1468 (CH2 bending), 1337 (sym.
NO2 bending), 1314 (C-N Strech), 694 (C-S stretch) cm-1.
1H-NMR spectroscopy
1H-NMR spectroscopy
1H-NMR (CDCl3) (δ, ppm): 8.66 (s,1H,-CONH-), 8.35-7.95 (m, 3H,
benzthiazole ring protons), 7.79-6.63 (m, 4H, phenyl ring protons), 5.91
(s, 1H, thiazole ring protons at phenyl linkage), 5.35 (s,1H,-C6H4-OH),
4.35 (s, 2H,-SCH2-), 3.95-3.83 (s, 2H, thiazole ring protons).
1H-NMR (CDCl3) (δ, ppm): 8.62 (s,1H,-CONH-), 8.34-7.96 (m, 3H,
benzthiazole ring protons), 7.75-7.56 (m, 4H, phenyl ring protons),
5.93 (s, 1H, thiazole ring protons at phenyl linkage), 4.35 (s, 2H,-
SCH2-), 3.95-3.83(s, 2H, thiazole ring protons).
13C-NMR spectroscopy
13C-NMR spectroscopy
13C-NMR (CDCl3) (δ, ppm): 171.1 (C=O, amide carbon), 170.4 (C=O
thiazole ring carbon), 164.2 (C=N bezthiazole ring carbon at sulfur
linkage), 154.6 (C-N benzthiazole ring carbon), 156.3 (phenyl ring
carbon at hydroxyl linkage), 141.2-145.4 (bezthiazole ring carbons at
sulfur and nitro linkage), 131.3 (phenyl ring carbon at thiazole linkage),
124.2-130.7 (phenyl ring carbons), 117.3-122.9 (benzthiazole ring
carbons at proton linkage), 58.4 (thiazole ring carbon at phenyl linkage),
41.8 (-S-CH2-CONH-), 37.2 (thiazole ring carbon at-C=O linkage).
13C-NMR (CDCl3) (δ, ppm): 171.9 (C=O, amide carbon), 168.8 (C=O
thiazole ring carbon), 164.9 (C=N bezthiazole ring carbon at sulfur
linkage), 155.2 (C-N benzthiazole ring carbon), 147.8 (phenyl ring
carbon at nitro linkage), 145.9 (phenyl ring carbon at thiazole
linkage), 134.3-135.5 (bezthiazole ring carbons at sulfur and nitro
linkage), 141.6-145.9 (benzthiazole ring carbons at proton linkage),
121.6-129.8 (phenyl ring carbons), 58.1 (thiazole ring carbon at
phenyl linkage), 41.3 (-S-CH2-CONH-), 36.5 (thiazole ring carbon at-
C=O linkage).
Mass spectroscopy
Mass spectroscopy
Molecular ion peak demonstrated on mass spectrum and reported
m/e (ESI): 463 (M+).
Molecular ion peak demonstrated on mass spectrum and reported
m/e (ESI): 492 (M+).
(G) N-(2-(4-methoxyphenyl)-4-oxothiazolidin-3-yl)-2-(5-nitro-
benzo[d]thiazol-2-ylthio) acetamide [compound 7g]
(I) 2-(6-nitrobenzo[d]thiazol-2-ylthio)-N-(4-oxo-2-
phenylthiazolidin-3-yl)acetamide [compound 7i]
Yield: 69.1 %; M. P. 207-209 °C; Anal. Cal. for C19H16N4O5S3: C,
47.89; H, 3.38; N, 11.76; O, 16.79; S, 20.19%; found: C, 47.92; H, 3.34;
N, 11.73; O, 16.81; S, 20.21%.
Yield: 56.8 %; M. P. 161-163 °C; Anal. Cal. for C18H14N4O4S3: C,
48.42; H, 3.16; N, 12.55; O, 14.33; S, 21.54%; found: C, 48.45; H, 3.12;
N, 12.52; O, 14.36; S, 21.55%.
FT-IR spectroscopy
FT-IR spectroscopy
FT-IR (νmax): 3268 (N-H strech.), 3037 (aromatic C-H strech.), 2972
(asym. aliphatic C-H strech.), 2865 (sym. aliphatic C-H strech.),
1670-2000 (overtone for substitution on aromatic ring), 1713
(cyclic C=O strech.), 1663 (amide C=O stretch.), 1602 (phenyl ring
stretch.), 1577 (N-H bending), 1539 (asym. N=O strech), 1512
(phenyl C-H out of plane bending), 1463 (CH2 bending), 1452 (asym
CH3 bending), 1384 (sym. CH3 bending), 1344 (Sym. N=O strech),
1316 (C-N Strech), 1254 (asym. C-O strech.), 1040 (sym. C-O
stretch.), 696 (C-S stretch) cm-1.
FT-IR (νmax): 3267 (N-H strech.), 3036 (aromatic C-H strech.), 2969
(asym. aliphatic C-H strech.), 2868 (sym. aliphatic C-H strech.),
1670-2000 (overtone for substitution on aromatic ring), 1716
(cyclic C=O strech.), 1668 (amide C=O stretch.), 1605 (phenyl ring
stretch.), 1584 (N-H bending), 1539 (asym. N=O strech), 1516
(phenyl C-H out of plane bending), 1469 (CH2 bending), 1345 (sym.
N=O strech), 1319 (C-N Strech), 694 (C-S stretch) cm-1.
1H-NMR spectroscopy
1H-NMR spectroscopy
1H-NMR (CDCl3) (δ, ppm): 9.17 (s, 1H,-CONH-), 8.34-8.25 (m, 3H,
benzthiazole ring protons), 7.37-7.18 (m, 5H, phenyl ring protons),
5.93 (s, 1H, thiazole ring protons at phenyl linkage), 4.35 (s, 2H,-
SCH2-), 3.95-3.83(s, 2H, thiazole ring protons).
1H-NMR (CDCl3) (δ, ppm): 8.62 (s,1H,-CONH-), 8.35-7.95 (m, 3H,
benzthiazole ring protons), 7.84-6.85 (m, 4H, phenyl ring protons),
5.92 (s, 1H, thiazole ring protons at phenyl linkage), 4.35 (s, 2H,-
SCH2-), 3.95-3.83 (s, 2H, thiazole ring protons).
13C-NMR spectroscopy
13C-NMR spectroscopy
13C-NMR (CDCl3) (δ, ppm): 173.1 (C=O, amide carbon), 169.9 (C=O
thiazole ring carbon), 166.5 (C=N bezthiazole ring carbon at sulfur
linkage), 159.6 (C-N benzthiazole ring carbon), 140.8 (phenyl ring
carbon at thiazole linkage), 142.4-146.6 (bezthiazole ring carbons at
sulfur and nitro linkage), 125.3-128.9 (phenyl ring carbons), 118.3-
123.5 (benzthiazole ring carbons at proton linkage), 59.2 (thiazole
ring carbon at phenyl linkage), 43.2 (-S-CH2-CONH-), 36.8 (thiazole
ring carbon at-C=O linkage).
13C-NMR (CDCl3) (δ, ppm): 171.4 (C=O, amide carbon), 169.2 (C=O
thiazole ring carbon), 164.1 (C=N bezthiazole ring carbon at sulfur
linkage), 154.1 (C-N benzthiazole ring carbon), 159.5 (phenyl ring
carbon at methoxy linkage), 141.3-145.4 (bezthiazole ring carbons at
sulfur and nitro linkage), 131.2 (phenyl ring carbon at thiazole linkage),
124.6-129.3 (phenyl ring carbons), 117.3-122.9 (benzthiazole ring
carbons at proton linkage), 57.9 (thiazole ring carbon at phenyl linkage),
41.4 (-S-CH2-CONH-), 36.4 (thiazole ring carbon at-C=O linkage).
Mass spectroscopy
Mass spectroscopy
Molecular ion peak demonstrated on mass spectrum and reported
m/e (ESI): 447 (M+).
Molecular ion peak demonstrated on mass spectrum and reported
m/e (ESI): 477 (M+).
(H) 2-(5-nitrobenzo[d]thiazol-2-ylthio)-N-(2-(3-nitrophenyl)-4-
oxothiazolidin-3-yl) acetamide [compound 7h]
(J) N-(2-(4-hydroxyphenyl)-4-oxothiazolidin-3-yl)-2-(6-
nitrobenzo[d]thiazol-2-ylthio) acetamide [compound 7j]
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Sunil et al.
Int J Pharm Pharm Sci, Vol 9, Issue 2, 60-68
Yield: 61.3 %; M. P. 179-181 °C; Anal. Cal. for C18H14N4O5S3: C,
46.74; H, 3.05; N, 12.11; O, 17.30; S, 20.80 %; found: C, 46.76; H,
3.01; N, 12.08; O, 17.33; S, 20.82%.
Molecular ion peak demonstrated on mass spectrum and reported
m/e (ESI): 477 (M+).
(L) 2-(6-nitrobenzo[d]thiazol-2-ylthio)-N-(2-(3-nitrophenyl)-4-
oxothiazolidin-3-yl) acetamide [compound 7l]
FT-IR spectroscopy
FT-IR (νmax): 3472 (O-H stretch.), 3278 (N-H strech.), 3042
(aromatic C-H strech.), 2973 (asym. aliphatic C-H strech.), 2869
(sym. aliphatic C-H strech.), 1670-2000 (overtone for substitution
on aromatic ring), 1714 (cyclic C=O strech.), 1667 (amide C=O
stretch.), 1599 (phenyl ring stretch.), 1581 (N-H bending), 1541
(asym. N=O strech), 1511 (phenyl C-H out of plane bending), 1466
(CH2 bending), 1345 (sym. N=O strech), 1316 (C-N Strech), 692 (C-S
stretch) cm-1.
Yield: 71.9 %; M. P. 269-271 °C; Anal. Cal. for C18H13N5O6S3: C,
43.98; H, 2.67; N, 14.25; O, 19.53; S, 19.57 %; found: C, 44.01; H,
2.64; N, 14.21; O, 19.56; S, 19.58 %.
FT-IR spectroscopy
FT-IR (νmax): 3265 (N-H strech.), 3043 (aromatic C-H strech.), 2978
(asym. aliphatic C-H strech.), 2873 (sym. aliphatic C-H strech.),
1670-2000 (overtone for substitution on aromatic ring), 1715
(cyclic C=O strech.), 1664 (amide C=O stretch.), 1601 (phenyl ring
stretch.), 1575 (N-H bending), 1543 (asym. NO2 strech), 1515
(phenyl C-H out of plane bending), 1466 (CH2 bending), 1339 (sym
NO2 bending), 1317 (C-N Strech), 694 (C-S stretch) cm-1.
1H-NMR spectroscopy
1H-NMR (CDCl3) (δ, ppm): 9.16 (s,1H,-CONH-), 8.34-7.96 (m, 3H,
benzthiazole ring protons), 7.77-6.63 (m, 4H, phenyl ring protons),
5.93 (s, 1H, thiazole ring protons at phenyl linkage), 5.35 (s,1H,-
C6H4-OH), 4.35 (s, 2H,-SCH2-), 3.95-3.83 (s, 2H, thiazole ring
protons).
1H-NMR spectroscopy
1H-NMR (CDCl3) (δ, ppm): 9.16 (s, 1H,-CONH-), 8.34-7.96 (m, 3H,
benzthiazole ring protons), 7.75-7.56 (m, 4H, phenyl ring protons),
5.93 (s, 1H, thiazole ring protons at phenyl linkage), 4.35(s, 2H,-
SCH2-), 3.95-3.83 (s, 2H, thiazole ring protons).
13C-NMR spectroscopy
13C-NMR (CDCl3) (δ, ppm): 173.3 (C=O, amide carbon), 172.2 (C=O
thiazole ring carbon), 165.2 (C=N bezthiazole ring carbon at sulfur
linkage), 160.2 (C-N benzthiazole ring carbon), 157.7 (phenyl ring
carbon at hydroxyl linkage), 143.6-146.8 (bezthiazole ring carbons
at sulfur and nitro linkage), 132.4 (phenyl ring carbon at thiazole
linkage), 125.7-130.9 (phenyl ring carbons), 118.6-123.8
(benzthiazole ring carbons at proton linkage), 59.3 (thiazole ring
carbon at phenyl linkage), 43.2 (-S-CH2-CONH-), 38.6 (thiazole ring
carbon at-C=O linkage).
13C-NMR spectroscopy
13C-NMR (CDCl3) (δ, ppm): 172.7 (C=O, amide carbon), 170.1 (C=O
thiazole ring carbon), 164.7 (C=N bezthiazole ring carbon at sulfur
linkage), 161.4 (C-N benzthiazole ring carbon), 149.7 (phenyl ring
carbon at nitro linkage), 146.6 (phenyl ring carbon at thiazole
linkage), 135.9-137.1 (bezthiazole ring carbons at sulfur and nitro
linkage), 142.9-146.2 (benzthiazole ring carbons at proton linkage),
121.9-129.4 (phenyl ring carbons), 59.4 (thiazole ring carbon at
phenyl linkage), 43.1 (-S-CH2-CONH-), 38.3 (thiazole ring carbon at-
C=O linkage).
Mass spectroscopy
Molecular ion peak demonstrated on mass spectrum and reported
m/e (ESI): 463 (M+).
Mass spectroscopy
(K) N-(2-(4-methoxyphenyl)-4-oxothiazolidin-3-yl)-2-(6-nitro-
benzo[d]thiazol-2-ylthio) acetamide [compound 7k]
Molecular ion peak demonstrated on mass spectrum and reported
m/e (ESI): 492 (M+).
Yield: 67.7 %; M. P. 202-204 °C; Anal. Cal. for C19H16N4O5S3: C,
47.89; H, 3.38; N, 11.76; O, 16.79; S, 20.19 %; found: C, 47.92; H,
3.34; N, 11.73; O, 16.81; S, 20.21 %.
Evaluation of antidiabetic activity in alloxan-induced diabetic rats
The LD50 values of the synthesised compounds were estimated to
be in the range of 300-3000 mg/kg b.w. Alloxan induces diabetes
through rapid depletion of β-cells which ultimately results to reduce
the insulin release. All the results summarised in table 2 revealed
that most of the synthesised compounds exhibited antidiabetic
response at the end of ten-day of the experimental period. It has
been found that oral administration of synthesised compounds 7d,
7g, 7h and 7l caused a more significant reduction in blood glucose
than other compounds in diabetic rats. However, the compound 7d
at 350 mg/kg b.w. exerted maximum glucose lowering effects
whereas 7c showed minimum glucose lowering effects.
FT-IR spectroscopy
FT-IR (νmax): 3271 (N-H strech.), 3040 (aromatic C-H strech.), 2976
(asym. aliphatic C-H strech.), 2868 (sym. aliphatic C-H strech.),
1670-2000 (overtone for substitution on aromatic ring), 1716
(cyclic C=O strech.), 1666 (amide C=O stretch.), 1604 (phenyl ring
stretch.), 1577 (N-H bending), 1542 (asym. N=O strech), 1514
(phenyl C-H out of plane bending), 1467 (CH2 bending), 1456 (asym
CH3 bending), 1386 (sym. CH3 bending), 1347 (sym. N=O strech),
1316 (C-N strech), 1253 (asym. C-O strech.), 1041 (sym. C-O
stretch.), 693 (C-S stretch) cm-1.
DISCUSSION
1H-NMR spectroscopy
This study was undertaken; mainly to assess the protective effect of
benzothiazole derivatives against alloxan-induced diabetes in
experimental rats. Alloxan is selectively toxic to pancreatic β cells
that produce insulin due to the accumulation of alloxan through the
GLUT2 transporter. Though alloxan by itself is not toxic, but once it
is infiltrated to the pancreatic β-cells through the GLUT2
transporter, alloxan is reduced to dialuric acid in the presence of
different cellular reducing agents. The presence of both alloxan and
its reduction product leads to the establishment of redox cycle for
generation of superoxide radicals. The toxic action of alloxan on β
cells is initiated by free radicals formed by redox reactions. The
intolerable rise in oxidative agents provokes necrosis of pancreatic
β-cells known to be vulnerable to a redox imbalance. This suggests
that alloxan diabetogenicity is a free radical-mediated process.
Furthermore, alloxan toxicity is related to animal death due to fatal
hypoglycemic convulsions. This study shows that oral
administration of synthesised benzothiazole derivatives prevented
the diabetogenic effect of alloxan; this is possibly due to the
1H-NMR (CDCl3) (δ, ppm): 9.16 (s,1H,-CONH-), 8.34-7.96 (m, 3H,
benzthiazole ring protons), 7.86-6.66 (m, 4H, phenyl ring protons),
5.92 (s, 1H, thiazole ring protons at phenyl linkage), 4.35 (s, 2H,-
SCH2-), 3.95-3.83 (s, 2H, thiazole ring protons).
13C-NMR spectroscopy
13C-NMR (CDCl3) (δ, ppm): 172.5 (C=O, amide carbon), 169.9 (C=O
thiazole ring carbon), 165.5 (C=N bezthiazole ring carbon at sulfur
linkage), 161.8 (C-N benzthiazole ring carbon), 158.8 (phenyl ring
carbon at methoxy linkage), 141.9-146.2 (bezthiazole ring carbons
at sulfur and nitro linkage), 132.1 (phenyl ring carbon at thiazole
linkage), 124.1-128.9 (phenyl ring carbons), 118.1-123.2
(benzthiazole ring carbons at proton linkage), 58.4 (thiazole ring
carbon at phenyl linkage), 42.1 (-S-CH2-CONH-), 37.3 (thiazole ring
carbon at-C=O linkage).
Mass spectroscopy
66

Sunil et al.
Int J Pharm Pharm Sci, Vol 9, Issue 2, 60-68
presence of antioxidant compounds, which act by inhibiting alloxan-
induced free radicals production [18, 19].
showed minimum glucose lowering effects. This study reveals the
result of test groups when significantly compared with positive
control (alloxan 120 mg/kg) p. o. and standard glibenclamide 10
mg/kg (p. o.). In addition, it is necessary to ensure, to determine the
exact mechanism by applying other in vitro methods for evaluation
of the antidiabetic activity. Effective blood glucose control is the key
for preventing or reversing diabetic complications and improving
the quality of life in patients with diabetes. Thus, sustained
reduction in hyperglycemia will decrease the risk of developing
microvascular complications and most likely reduce the risk of
macrovascular complications [20].
All the synthesised derivatives were confirmed by FTIR, 1H NMR,
13CNMR and mass spectroscopy method. The animals showing blood
glucose range of 200-400 mg dL-1 were used for the experiment and
the hyperglycemia was confirmed after 72 h of alloxan monohydrate
administration (i. p.). It has been found that oral administration of
synthesised compounds specifically 7d, 7g, 7h and 7l at a defined
dose of 350 mg/kg b.w. caused a more significant reduction in blood
glucose than other compounds in diabetic rats. However, the
compound 7d exerted maximum glucose lowering effects whereas 7i
Table 3: Antidiabetic activity of synthesised compounds 7(a–l)
Blood glucose level (mg/dl)
S. No.
Treatment
% reduction in blood glucose
0th day
7th day
14th day
102±0.9
271±1.4
168±1.8
206±1.3
191±0.8
199±1.9
167±2.2˙˙
192±1.3
205±1.6
174±1.4
179±1.5
210±0.5
192±2.2
199±1.9
186±1.1
21st day
100±1.2
270±1.9
95±1.7
(350 mg/kg b. w p. o)
1.
Normal control
105.09±1.2
274±1.3
278±2.1
274±1.4
271±2.7
270±1.9
279±3.6
281±2.8
272±1.7
283±1.3
281±4.2
276±3.4
273±1.6
269±2.8
274±1.5
102±0.3
273±1.6
219±2.4
243±2.8
235±3.1
246±2.7
222±3.4˙
238±2.9
254±3.2
230±2.5
235±2.7˙
250±2.2
240±2.6
244±2.3
242±2.5˙˙
-
-
2.
Diabetic positive control
3.
Glibenclamide 10 mg/kg
65.82 %
42.33 %
46.86%
40.37 %
63.44 %
46.97 %
41.54%
61.13 %
59.43 %
40.21 %
50.18 %
45.72 %
55.10 %
4.
7a
7b
7c
7d
7e
7f
7g
7h
7i
158±2.3
144±3.3
161±1.5
102±1.8˙˙˙
149±4.1
159±2.9
110±3.1˙˙˙
114±2.6˙˙
165±3.2
136±2.4
146±2.1
123±1.8˙˙
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
7j
7k
7l
n=6, Values are expressed as mean±SD, ˙P<0.05, ˙˙P<0.01, ˙˙˙P<0.001–significant compared to standard group
Researchers also synthesised a novel series of substituted (E)-3-
(Benzo[d]thiazol-2-ylamino) phenylprop-2-en-1-ones and evaluated
for their antidiabetic activity [21]. Selective inhibitors of 11beta-
Stretch: Stretching, Sym: Symmetric, Asym: Asymmetric.
CONFLICTS OF INTERESTS
hydroxysteroid dehydrogenase type
1
(11β-HSD1) have
All the authors have no conflicts of interests.
REFERENCES
considerable potential as treatments for metabolic diseases, such as
diabetes mellitus type 2 or obesity. Moreover, a series of novel
benzothiazole derivatives were synthesised and studied for their
inhibitory activities against 11-HSD1 from human hepatic
microsomes measured using a radioimmunoassay (RIA) method
[22]. Benzothiazole derivatives of thiazolidinones were synthesised
and assayed for activity on Peroxisome proliferator-activated
receptor (PPAR) subtypes and inhibitory activity of NO production
in lipopolysaccharide-activated macrophages. Most of the
compounds were identified as PPARγ agonist, indicating their
potential as drug candidate for diabetes [23].
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diabetes mellitus. Int J Curr Pharm Res 2016;8:16-8.
2. Malang M, Kayal G, Kharia A. Comparative study of
heterocyclics in the treatment of diabetes. World J Pharm
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Pharm Sci Drug Res 2011;3:1-7.
CONCLUSION
The diabetic hyperglycemia induced by alloxan produces an
elevation of plasma levels of glucose, which is considered significant
marker of renal dysfunction. The benzothiazole derivatives were
synthesised by sequencing scheme and subsequently confirmed by
different spectroscopy methods. The different physicochemical
properties were characterised and then the synthesised derivatives
were evaluated for their anti-diabetic activity in an alloxan-induced
diabetic rat model. Amongst all these synthesised derivatives
compound 7d demonstrated more potent anti-diabetic activity at
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declared no conflict of interest.
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How to cite this article
•
Sunil Kumar, DS Rathore, Gopal Garg, Kapil Khatri, Rahul
Saxena, Sanjeev K Sahu. Synthesis and evaluation of some
benzothiazole derivatives as antidiabetic agents. Int J Pharm
Pharm Sci 2017;9(2):60-68.
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