Synthesis, in vitro evaluation and molecular docking studies of thiazole derivatives as new inhibitors of α-glucosidase

Article abstract of DOI:10.1016/j.bioorg.2015.06.006

A series of thiazole derivatives 1-21 were prepared, characterized by EI-MS and ¹H NMR and evaluated for α-glucosidase inhibitory potential. All twenty one derivatives showed good α-glucosidase inhibitory activity with IC₅₀ value ran

Full text of DOI:10.1016/j.bioorg.2015.06.006

Accepted Manuscript
Synthesis, in vitro evaluation and molecular docking studies of thiazole deriv-
atives as new inhibitors of α-glucosidase
Fazal Rahim, Hayat Ullah, Muhammad Tariq Javid, Abdul Wadood,
Muhammad Taha, Muhammad Ashraf, Ayesha Shaukat, Muhammad Junaid,
Shafqat Hussain, Wajid Rehman, Rashad Mehmood, Muhammad Sajid,
Muhammad Naseem Khan, Khalid Mohammed Khan
PII:
S0045-2068(15)30002-X
DOI:
http://dx.doi.org/10.1016/j.bioorg.2015.06.006
YBIOO 1826
Reference:
Bioorganic Chemistry
To appear in:
Received Date:
Revised Date:
Accepted Date:
23 April 2015
15 June 2015
26 June 2015
Please cite this article as: F. Rahim, H. Ullah, M.T. Javid, A. Wadood, M. Taha, M. Ashraf, A. Shaukat, M. Junaid,
S. Hussain, W. Rehman, R. Mehmood, M. Sajid, M.N. Khan, K.M. Khan, Synthesis, in vitro evaluation and
molecular docking studies of thiazole derivatives as new inhibitors of α-glucosidase, Bioorganic Chemistry (2015),
doi: http://dx.doi.org/10.1016/j.bioorg.2015.06.006
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Synthesis, in vitro evaluation and molecular docking studies of thiazole derivatives
as new inhibitors of α-glucosidase
Fazal Rahim,a Hayat Ullah,a Muhammad Tariq Javid,a Abdul Wadood,b Muhammad
Taha,c,d Muhammad Ashraf,e Ayesha Shaukat,e Muhammad Junaid,b Shafqat Hussain,f
Wajid Rehman,a Rashad Mehmood,g Muhammad Sajid,h Muhammad Naseem Khan,a and
Khalid Mohammed Khanf
aDepatment of Chemistry, Hazara University, Mansehra-21120, Pakistan
bDepartment of Biohemistry, Abdul Wali Khan University Mardan, Mardan-23200, Pakistan.
c
Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA , Puncak Alam
Campus,
d Faculty of Applied Science Universiti Teknologi MARA, 40450 Shah Alam, Selangor D. E. Malaysia,
eDepartment of Biochemistry and Biotechnology, The Islamia University of Bahawalpur, Bahawalpur
63100. Pakistan
fH. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences,
University of Karachi, Karachi-75270, Pakistan
gDepatment of Conservation Studies, Hazara University, Mansehra-21120, Pakistan
hDepartment of Biochemistry, Hazara University, Mansehra-21120, Pakistan.
Abstract
A series of thiazole derivatives 1-21 were prepared, characterized by EI-MS and 1HNMR
and evaluated for α-glucosidase inhibitory potential. All twenty one derivatives showed
good α-glucosidase inhibitory activity with IC50 value ranging between 18.23±0.03 to
424.41 ± 0.94 μM when compared with the standard acarbose (IC50, 38.25 ± 0.12 μM).
Compound (8) (IC50, 18.23 ± 0.03 μM) and compound (7) (IC50 = 36.75 ± 0.05 μM)
exhibited outstanding inhibitory potential much better than the standard acarbose (IC50,
38.25 ± 0.12 μM). All other analogs also showed good to moderate enzyme inhibition.
Molecular docking studies were carried out in order to find the binding affinity of
thiazole derivatives with enzyme. Studies showed these thiazole analogs as a new class of
α-glucosidase inhibitors.
Keywords: Thiazole, Synthesis, Molecular docking, α-Glucosidase inhibition.
*Corresponding Author: fazalstar@gmail.com, Tel.: 0092-335-9528343;
1

1. Introdcution
α-Glucosidase (EC. 3.2.1.20) is a membrane-bound enzyme located at the epithelium of
the small intestine [1]. It specifically hydrolyzed the α-glucopyranoside bond, thus
releasing a/an α-D-glucose from the non-reducing end of the sugar [2]. It plays role in
carbohydrates digestion and glycoprotein processing. Its inhibitors are be used to treat
diabetics, HIV and cancers [3,4]. Clinical trials showed that the α-glucosidase inhibitors
improved long-term glycemic control as measured by decreased hemoglobin A1c
(HbA1c) in patients with type II diabetes and delayed the development of type II diabetes
in patients with impaired glucose tolerance [5]. Recently, there had been widespread
interest in α-glucosidase inhibitors, partly because of their potential as therapeutic targets,
especially the inhibition of these enzymes had been found to help control postprandial
blood glucose levels in diabetic patients [6,7], and can have profound effects on
maturation, transport, and secretion of glycoproteins and can alter cell-cell recognition
processes [8-10].
Several sugar α-glucosidase inhibitors, including acarbose, voglibose, and miglitol are
clinically used in the effective treatment of type-2 diabetes mellitus [11]. However, such
inhibitors, which are of great structural diversity, require tedious multi-steps for
preparation. Amongst the various types of glucosidase inhibitors, also non-sugar
derivatives have drawn considerable attention. Indeed, there is great structural diversity
amongst glucosidase inhibitors, which are not based on a sugar scaffold [12-14].
In addition, α-glucosidase inhibitors may serve as a viable tool for better understanding
of some biochemical processes in which α-glucosidase functions [15].
The thiazole and its derivatives are very much important in nature because they are
present in thiamine that acts as a coenzyme for the oxidative decarboxylation of α-keto
acids. It is also present in the skeleton of penicillin which is the most significant and the
first one of the broad spectrum antibiotics [16]. Thiazole containing molecules such as
sulfathiazole is used as an antimicrobial drug, ritonavir as antiretroviral drug, abafungin
as antifungal drug, bleomycine and thiazofurin as antineoplastic drugs [17,18]. Thiazole
containing compounds such as nizatidine is used as antihistaminic, niridazole as
schistosomicidal and nitazoxanide as antiprotozoal [19].
2

Our research group is in struggle to discovered new biologically important scaffold which
are simple molecules, easy to synthesize, high yielding and have no boring chemistry. In
a continued effort in search for biologically active molecules [20-27], here we are
reporting synthesis of thiazole derivatives and their α-glucosidase inhibition activity not
published earlier.
2.0. Result Discussion
2.1. Chemistry
The synthesis of thiazole derivatives 1-21 (Scheme 1) was carried out by two-step
reactions. In the first step, different substituted benzaldehyde/acetophenone (1 mmol) was
mixed with thiosemicarbazide (1 mmol) in methanol in the presence of few drops of
glacial acetic acid and refluxed for 3-5 hours. Completion of reaction was checked by
periodic TLC. After completion of reaction, it was filtered and washed with methanol to
obtained pure product in poor yield to good yield 0.175g to 0.300g depending on
different attached substituents.
In second step, the product obtained in the first step (1 mmol) was mixed and refluxed
with chloro or methoxy phencyl bromide (1 mmol) for 3-5 hours. Completion of reaction
was monitored by periodic TLC. After completion of reaction, the reaction mixture was
filtered and washed with hexane; pure product was obtained in good yield. The structures
of all derivatives (1-21) were confirmed by different spectroscopic techniques, such as 1H
NMR and EI-MS.
Insert Scheme-1 here
Insert Table 1 here
2.2. α-Glucosidase inhibition
Compounds 1-21 showed a variable degree of α-glucosidase inhibition with IC50 value
ranging between 18.23 ± 0.03 to 424.41 ± 0.94 μM when compared with standard
acarbose (IC50 = 38.25 ± 0.12 μM).
Out of these 21 analogues, two compounds exhibited potent α-glucosidase inhibition.
Compound 8 (IC50 = 18.23 ± 0.03 μM) and 7 (IC50 = 36.75 ± 0.05 μM) exhibited
outstanding activity better than the standard acarbose.
3

Compounds 2, 21, 18, 9 and 16 also showed good inhibition with IC50 value 43.26 ± 0.07,
46.39±0.05, 55.43 ± 0.08, 68.52 ± 0.08 and 99.16 ± 0.51 μM respectively. All other
derivatives also showed good to moderate activities. The order of increase IC50 values of
remaining compounds is as 17 < 14 <6 <20 <11 <13 <15 <5 <1 <19 <3 <10 <4 <12.
The most active analog among the series is 8 having 4-OH at R1 and 4-Cl at R3. The
second most active compound is 7 having 4-benzyloxy group at R1 and 4-Cl at R3. From
this study it was observed that by changing substituents at R1 and R3 greatly influence the
potential of compounds.
The molecular docking studies were performed in order to know the mechanism of
enzyme inhibition and binding interaction of these thiazole analog inside the binding
pocket of α-glucosidase.
2.3. Molecular modeling and docking studies
The resulting anti-α-glucosidase activity of the tested compounds, especially compound 8
along with control acarbose prompted us to perform molecular docking study to
understand the ligand-protein interactions in detail. The compound 8 and acarbose were
docked into the active site of α-glucosidase (Asp214, Glu276, Asp 349 and Arg439) [28].
In general, the most active compound 8 formed three strong hydrogen bonds with active
site residues (one with Glu276 and two with Arg439). As the number of hydrogen bond
increased, it contributes toward the total strength of hydrogen bonding network. In case
of compound 8, along with the important residues in the pocket, one additional hydrogen
bond is formed with pocket residue Asn347 (Figure-1). As the total number of hydrogen
bonds become four hence compound 8 exhibited good fitting inside the pocket site with
docking score -11.4139.
Insert Figure-1 here
The control, Acarbose, make three hydrogen bonds with the active site residues Asp214,
Glu276 and Asp349.The strength of hydrogen bonds made by acarbose is relatively
strong as compared to compound 8 but due to its bulky size it has some clashes with
Arg439, Phe158 and leu218. Therefore, these clashes reduce its activity as compared to
compound 8. These results were also confirmed by the docking score. The control,
4

acarbose, due to its clashes didn’t fit well in the pocket and hence have a docking score -
9.177 while compound 8 has a good docking score -11.4139 Figure-2.
Insert Figure-2 here
The compound 12 is the least active and did not form hydrogen bonds with pocket
residues (Figure-3).
Insert Figure-3 here
2.4. α-Glucosidase Assay
The α-glucosidase inhibition activity was performed with slight modifications as given by
Pierre et al. Total volume of 100 μL reaction mixture contained 70 μL 50 mM phosphate
buffer pH 6.8, 10 μL test compound (0.5 mM in methanol) followed by the addition of 10
μL enzyme solution (0.057 units, Sigma Inc.) in the buffer. The contents were mixed,
pre-incubated for 10 min at 37 ºC and pre-read at 400 nm. The reaction was initiated by
the addition of 10 μL of 0.5 mM substrate (p-nitrophenyl glucopyranoside, Sigma Inc.).
After 30 min of incubation at 37ºC, absorbance of p-nitrophenol released was measured
using Synergy HT 96-well plate reader, BioTek, USA. Acarbose was used as positive
control. All experiments were carried out in triplicates. The percent inhibition was
calculated by the following equation:
Inhibition (%) = (Abs of Control – Abs of Test / Abs of Control) × 100
Active compound solutions were suitably diluted and their inhibition studies were
determined. Data obtained was used for the determination of IC50 values (concentration at
which there is 50% enzyme inhibition) using EZ-Fit Enzyme Kinetics Software (Perrella
Scientific Inc. Amherst, USA) [30]
3.0. Conclusion
Thiazole compounds (1-21) have been synthesized and evaluated for their α-glucosidase
inhibitory potential. All compounds showed varying degree inhibitory potential.
Compound 7 and 8 were found potent among the series with IC50 value 36.75±0.05 and
18.23±0.03 μM respectively, as compared to standard acarbose (IC50, 38.25±0.12 μM).
Consequently in silico studies were performed to recognize the binding mode of these
compounds. The structures of all derivatives (1-21) were confirmed by different
spectroscopic techniques such as 1H NMR and EI-MS.
5

4. Materials and methods
NMR spectra were obtained with AVANCE AV 300 MHZ spectrometers. NMR spectra
were recorded by using DMSO and acetone as solvent. TMS was used as internal
standard. Finnegan MAT-311A spectrometer was used for electron impact mass spectra
(EI-MS) analysis. Cesium iodide was used as an internal standard for mass measurement.
All the above characterizations were performed at H.E.J Research Institute of Chemistry,
Karachi University Pakistan. Column chromatography was performed on silica gel (E.
Merck, type 60, 70-230 mesh). Pre-coated silica gel aluminum plates (Kieselgel 60,
2020 and 0.5 mm thick, E. Merck, Germany) were used for TLC analysis. Light of
wavelength 254 and 365 nm were used to visualize the chromatogram.
4.1. Computational Methods
The three dimensional structure of α-glucosidase for Saccharomyces cerevisiae has not
been solved up to yet. However, only a few homology models have been reported for
this enzyme previously [31-33]. The three dimensional coordinates of none of these
model are publically available. So an attempt was made to construct a 3D model of α-
glucosidase by homology modeling using the same protocol as described by Burke et al
based on the crystal structure of Saccrhromyces cerevisiae isomaltase (3AJ7.pdb) [33].
The amino acid sequence of α-glucosidase from Saccharomyces cerevisiae was retrieved
from UniProt protein resource data bank (http://www.uniprot.org/) under the access code
P53341. 3D structure was built using homology modeling tools implemented in MOE
2013. The constructed model was subjected to energy minimization upto 0.05 RMS
garadient using AMBER99 force field in order to get stable bond energies. The final
refine structure was then used for docking purpose. All the synthesized compounds were
sketched using Builder program implemented in MOE 2013 and were converted into their
respective 3D structure. Subsequently, the energy of compounds was minimized up to
0.05 gradients using the MMFF94x force field. All compounds were docked into active
pocket of α-glucosidase using the Triangular Matching docking method and 30
conformations of each compound were generated with docking score. Each complex was
analyzed for interactions and their 3D images were taken.
6

4.2. General procedure for synthesis of thiazole derivatives
The synthesis of thiazole derivatives 1-21 (Scheme 1) was carried out by two-step
reactions. In the first step, different substituted benzaldehyde/acetophenone (1 mmol) was
mixed with thiosemicarbazide (1 mmol) in methanol in the presence of few drops of
glacial acetic acid and refluxed for 3-5 hours. Completion of reaction was checked by
periodic TLC. After completion of reaction, it was filtered and washed with methanol to
obtained pure product in poor yield to good yield 0.175g to 0.300g depending on
different attached substituents.
In second step, the product obtained in the first step (1 mmol) was mixed and refluxed
with chloro or methoxy phencyl bromide (1 mmol) for 3-5 hours. Completion of reaction
was monitored by periodic TLC. After completion of reaction, the reaction mixture was
filtered and washed with hexane; pure product was obtained in good yield. The structures
of all derivatives (1-21) were confirmed by different spectroscopic techniques, such as 1H
NMR and EI-MS.
4.2.1. (E)-4-(4-Chlorophenyl)-2-(2-(3-nitrobenzylidene)hydrazinyl)thiazole (1)
Yield: 33%; Solid m.p. 257 °C; 1H-NMR: (DMSO-d6, 300 MHz): δ 12.4 (s, 1H, NH), 8.4
(br. s, 1H, H-2), 8.2 (dd, J4,6 = 1.2, J4,5 = 8.1 Hz , 1H, H-4), 8.1 (s, 1H, HC=N), 8.0 (d,
J6,5 = 7.8 Hz , 1H, H-6), 7.8 (d, J3″,2″/5″,6″ = 8.4 Hz , 2H, H-3″/5″), 7.7 (t, J5/4,6 = 8.1 Hz,
1H, H-5), 7.4 (m, 3H, H-5′/2″/6″); 13C NMR (75 MHz, DMSO-d6): 171.4, 150.3, 148.4,
143.1, 134.5, 134.1, 132.1, 131.0, 129.7, 129.1, 129.1, 128.6, 128.6, 126.0, 121.3, 105.2;
EI-MS: m/z (rel. int. %): 358 (M+, 51), 210 (100), 174 (43), 168 (52), 102 (15); MS: as
calculated 358.0291 and found 358.0286.
4.2.2.(E)-2-(2-(1-(2-Bromo-4-nitrophenyl)ethylidene)hydrazinyl)-4-(4-
chlorophenyl)thiazole
(2)
yield: 50%; Solid m.p. 262 °C; 1H-NMR: (DMSO-d6, 300 MHz): δ 12.8 (s, 1H, NH), 8.2
(m, 2H, H-3/5), 8.1 (d, J3″,2″/5″,6″ = 6.3Hz , 2H, H-3″/5″), 8.0 (m, 1H, H-6), 8.1 (d,
J2″,3″/6″,5″ = 8.7Hz , 2H, H-2″/6″), 7.5 (s, 1H, H-5′), 3.3 (s, 3H, Me); 13C NMR (75 MHz,
DMSO-d6): 171.4, 168.4, 152.2, 150.0, 141.5, 134.1, 132.2, 131.0, 129.1, 129.1, 128.6,
7

128.6, 126.5, 123.1, 122.4, 105.1, 16.2; EI-MS: m/z (rel. int. %): 449 (M+, 18), 221 (17),
149 (15), 137 (31), 83 (100); MS: as calculated 449.9553 and found 449.9545.
4.2.3. (E)-4-(4-Chlorophenyl)-2-(2-(2-nitrobenzylidene)hydrazinyl)thiazole (3)
Yield: 50%; Solid m.p. 260 °C; 1H-NMR: (DMSO-d6, 300 MHz): δ 12.5 (s, 1H, NH), 8.4
(s, 1H, HC=N), 8.0 (d, J3″, 2″/5″,6″ = 8.1 Hz , 2H, H-3″/5″), 8.0 (d, J3,4/6,5 = 8.4 Hz , 2H, H-
3/6), 7.7 (t, J4/3,5 = 7.5 Hz, 1H, H-4), 7.6 (t, J5/4,6 = 7.2 Hz, 1H, H-5), 7.4 (m, 3H, H-
5′/2″/6″); 13C NMR (75 MHz, DMSO-d6): 171.4, 150.1, 147.6, 143.1, 134.6, 134.1,
131.7, 131.0, 130.2, 129.1, 129.1, 128.6, 128.6, 128.2, 124.1, 105.2; EI-MS: m/z (rel. int.
%): 358 (M+, 54), 210 (100), 168 (91), 83 (68), 44 (56); MS: as calculated 358.0291 and
found 358.0295.
4.2.4. (E)-4-(4-Chlorophenyl)-2-(2-(1-(4-(piperidin-1-yl)phenyl)ethylidene)hydra-
zinyl)thiazole (4)
1
Yield: 43%; Solid m.p. 280 °C; H-NMR: (DMSO-d6, 300 MHz): δ 7.9 (m, 4H, H-
3″/5″/2/6), 7.4 (m, 4H, H-2″/6″/3/5), 7.2 (s, 1H, H-5′), 3.3 (s, 3H, Me), 3.0 (s, 10H, H-
13
2‴/3‴/4‴/5‴/6‴); C NMR (75 MHz, DMSO-d6): 171.6, 168.7, 151.8, 150.1, 134.2,
131.0, 130.0, 130.0, 129.1, 129.1, 128.7, 128.7, 127.0, 111.8, 111.8, 105.1, 54.7, 54.7,
25.4, 25.4, 24.3, 17.1; EI-MS: m/z (rel. int. %): 410 (M+, 54), 375 (20), 299 (29), 210
(100), 168 (91), 83 (68), 44 (56); MS: as calculated 410.1332 and found 410.1327.
4.2.5. (E)-4-((2-(4-(4-Chlorophenyl)thiazol-2-yl)hydrazono)methyl)-N,N-dimethyl-
aniline (5)
1
Yield: 38%; Solid m.p. 270 °C; H-NMR: (DMSO-d6, 300 MHz): δ 8.0 (s, 1H, HC=N),
7.8 (d, J3″,2″/5″,6″ = 6.3 Hz , 2H, H-3″/5″), 7.6 (m, 2H, H-2/6), 7.4 (d, J2″,3″/6″,5″ = 6.6 Hz ,
2H, H-2″/6″), 7.3 (d, J3,2 = 6.3 Hz , 1H, H-3), 7.2 (d, J5,6 = 6.3 Hz , 1H, H-5), 7.2 (s, 1H,
13
H-5′), 3.0 (s, 6H, 2Me); C NMR (75 MHz, DMSO-d6): 171.5, 153.2, 150.1, 143.2,
134.2, 131.0, 129.1, 129.1, 128.8, 128.8, 128.1, 128.1, 123.1, 111.8, 111.8, 105.0, 41.2,
41.2; EI-MS: m/z (rel. int. %): 356 (M+, 3), 210 (100), 168 (39), 147 (46), 43 (87); MS:
as calculated 356.0862 and found 356.0854.
4.2.6. (E)-4-(4-Chlorophenyl)-2-(2-(naphthalene-2-yl-methylene)hydrazinyl)thiazole (6)
8

1
Yield: 32%; Solid m.p. 276 °C; H-NMR: (DMSO-d6, 300 MHz): δ 8.3 (s, 1H, HC=N,
8.0 (d, J3″, 2″/5″,6″ = 8.4 Hz , 2H, H-3″/5″), 7.9 (m, 5H, H-2/3/4/5/8), 7.5 (m, 2H, H-7/6),
13
7.4 (d, J2″,3″/6″,5″ = 8.4 Hz , 2H, H-2″/6″), 7.2 (s, 1H, H-5′); C NMR (75 MHz, DMSO-
d6): 171.6, 150.1, 143.2, 134.2, 136.0, 133.8, 131.0, 129.1, 128.6, 128.6, 128.4, 128.0,
127.9, 127.9, 127.1, 126.8, 126.1, 126.1, 105.1; EI-MS: m/z (rel. int. %): 363 (M+, 18),
210 (87), 168 (35), 153 (100), 127 (33); MS: as calculated 363.0597 and found 363.0590.
4.2.7. (E)-2-(2-(4-(Benzyloxy)benzylidene)hydrazinyl)-4-(4-chlorophenyl)thiazole (7)
Yield: 81%; Solid m.p. 278 °C; 1H-NMR: (DMSO-d6, 300 MHz): δ 8.0 (s, 1H, HC=N),
7.8 (d, J3″,2″/5″,6″ = 6.3 Hz , 2H, H-3″/5″), 7.6 (d, J2″,3″/6″,5″ = 6.3 Hz , 2H, H-2″/6″), 7.4 (d,
J2,3/6,5 = 5.4 Hz , 2H, H-2/6), 7.3 (m, 5H, H-2‴/3‴/4″′/5″′/6″′), 7.2 (s, 1H, H-5′), 7.0 (d,
J3,2/5,6 = 6.6 Hz , 2H, H-3/5), 5.1 (s, 2H, OCH2); 13C NMR (75 MHz, DMSO-d6): 171.6,
161.2, 150.1, 143.2, 136.5, 134.2, 131.0, 130.1, 130.1, 129.1, 129.1, 128.7, 128.7, 128.7,
128.7, 127.5, 127.0, 127.0, 126.1, 114.2, 114.2, 105.1, 70.7; EI-MS: m/z (rel. int. %): 429
(M+, 17), 214 (53), 91 (100), 65 (22); MS: as calculated 419.0859 and found 419.0848.
4.2.8. (E)-2,6-Di-t-butyl-4-((2-(4-(4-Chlorophenyl)thiazole-2-yl)hydrazono)methyl)-
phenol (8)
1
Yield: 100%; Solid m.p. 287 °C; H-NMR: (DMSO-d6, 300 MHz): δ 7.9 (s, 1H, HC=N),
7.7 (d, J3″,2″/5″,6″ = 6.3 Hz , 2H, H-3″/5″), 7.4 (s, 2H, H-2/6), 7.0 (s, 1H, H-5′), 6.9 (d,
13
J2″,3″/6″,5″ = 6.6 Hz , 2H, H-2″/6″), 3.7 (s, 3H, OMe), 1.3 (s, 18H, 6Me); C NMR (75
MHz, DMSO-d6): 171.6, 150.1, 156.8, 143.2, 136.1, 136.1, 134.2, 131.0, 129.1, 129.1,
128.7, 128.7, 125.4, 123.6, 123.6, 105.1, 36.4, 36.1, 36.1, 36.1, 34.2, 34.2, 31.4, 31.4; EI-
MS: m/z (rel. int. %): 441 (M+, 18), 216 (35), 210 (100), 174 (37), 168 (59); MS: as
calculated 441.1642 and found 441.1650.
4.2.9.
1-((E)-(2-(4-(4-chlorophenyl)thiazol-2-yl)hydrazono)methyl)-3-((Z)-(2-(4-(4-
chlorophenyl)thiazol-2-yl)hydrazono)methyl)benzene (9)
1
Yield: 85%; Solid m.p. 278 °C; H-NMR: (DMSO-d6, 300 MHz): δ 12.2 (s, 2H, 2xNH),
8.0 (s, 2H, 2xHC=N), 7.8 (d, J3″,2″/5″,6″ = 8.4 Hz , 4H, 2xH-3″/5″), 7.6 (s, 2H, 2xH -5′), 7.4
13
(m, 8H, H-2/3/5/6, 2xH-2″/6″); C NMR (75 MHz, DMSO-d6): 171.6, 171.6, 150.1,
150.1, 143.1, 143.1, 136.1, 136.1, 134.2, 134.2, 133.7, 133.7, 131.4, 131.3, 129.2, 129.2,
129.2, 129.2, 128.7, 128.7, 128.7, 128.7, 128.6, 128.2, 105.1, 105.1; EI-MS: m/z (rel. int.
9

%): 549 (M+, 18), 338 (22), 210 (100), 168 (59), 82 (13); MS: as calculated 549.4973 and
found 549.4964.
4.2.10. 5-(4-chlorophenyl)-2-((E)-2-(4-((E)-(2-(4-(4-chlorophenyl)thiazol-2-
yl)hydrazono)methyl)benzylidene)hydrazinyl)thiazole (10)
1
Yield: 86%; Solid m.p. 290 °C; H-NMR: (DMSO-d6, 300 MHz): δ 10.4 (s, 2H, 2xNH),
8.2 (m, 4H, 2xHC=N, H-3″/5″), 7.8 (m, 6H, 2xH-2″/6″, H-3″/5″), 7.4 (m, 4H, H-2/4/5/6),
13
7.2 (s, 2H, 2x H-5′); C NMR (75 MHz, DMSO-d6): 171.6, 171.6, 150.1, 150.1, 143.2,
143.2, 134.2, 134.2, 133.7, 133.7, 131.3, 131.3; 131.0, 131.0, 129.1, 129.1, 129.1, 129.1,
128.7, 128.7, 128.7, 128.7, 128.3, 128.3, 105.1, 105.1; EI-MS: m/z (rel. int. %): 549 (M+,
20), 338 (17), 210 (100), 168 (38), 128 (36); MS: as calculated 549.4973 and found
549.4964.
4.2.11. (E)-5-((2-(4-(4-Chlorophenyl)thiazole-2-yl)hydrazono)methyl)-2-methoxy-phenol
(11)
1
Yield: 52%; Solid m.p. 281 °C; H-NMR: (DMSO-d6, 400 MHz): δ 8.1 (s, 1H, HC=N),
7.8 (d, J3″,2″/5″,6″ = 6.3 Hz , 2H, H-3″/5″), 7.4 (d, J2″,3″/6″,5″ = 6.3 Hz , 2H, H-2″/6″), 7.3 (m,
2H, H-2/5), 7.1 (dd, J 6,2 = 1.8, J6,5 = 6.3 Hz , 1H, H-6), 7.0 (s, 1H, H-5′); 13C NMR (75
MHz, DMSO-d6): 171.6, 152.1, 150.1, 147.1, 143.1, 134.2, 131.0, 130.1, 129.1, 129.1,
128.7, 128.7, 122.7, 115.8, 112.2, 105.1, 56.0; EI-MS: m/z (rel. int. %): 359 (M+, 18), 210
(60), 101 (32), 59 (81), 43 (100); MS: as calculated 359.0495 and found 359.0486.
4.2.12. (E)-4-(4-Methoxyphenyl)-2-(2-(1-(3- nitrophenyl)ethylidene)hydrazinyl)thia-zole
(12)
Yield: 74%; Solid m.p. 290 °C; 1H-NMR: (DMSO-d6, 300 MHz): δ 8.5 (s, 1H, H-2), 8.2
(t, J4/5,6 6/5,4 = 7.8 Hz, 2H, H-4/6), 7.8 (d, J2″,3″/6″,5″ = 8.7 Hz , 2H, H-2″/6″), 7.7 (t, J5/6,4
=
8.1 Hz, 1H, H-5), 7.1 (s, 1H, H-5′), 6.9 (d, J3″,2″/5″,6″ = 8.7 Hz , 2H, H-3″/5″), 3.7 (s, 3H,
13
OMe), 2.4 (s, 3H, Me); C NMR (75 MHz, DMSO-d6): 171.6, 168.6, 160.4, 150.1,
134.8, 134.2, 131.7, 131.7, 128.4, 128.4, 126.0, 126.4, 125.2, 114.7, 114.7, 105.1, 55.7,
17.0; EI-MS: m/z (rel. int. %): 368 (M+, 100), 205 (77), 164 (93), 149 (26), 82 (46); MS:
as calculated 368.4096 and found 368.4096.
4.2.13. (E)-2-(2-(Anthracen-9-ylmethylene)hydrazinyl)-4-(4-methoxyphenyl)thiazole (13)
10

Yield: 73%; Solid m.p. 277 °C; 1H-NMR: (DMSO-d6, 300 MHz): δ 12.3 (s, 1H, NH), 9.2
(s, 1H, HC=N), 8.6 (m, 3H, H-2/6/10), 8.1 (d, J5,4/7,8 = 8.1 Hz , 2H, H-5/7), 7.8 (d,
J2″,3″/6″,5″ = 8.4 Hz , 2H, H-2″/6″), 7.6 (m, 4H, H-3/4/8/9), 7.1 (s, 1H, H-5′), 6.9 (d,
13
J3″,2″/5″,6″ = 8.7 Hz , 2H, H-3″/5″), 3.7 (s, 3H, OMe); C NMR (75 MHz, DMSO-d6):
171.6, 160.5, 150.1, 143.2, 131.7, 131.7, 128.7, 128.7, 128.7, 128.4, 128.4, 128.0, 128.0,
128.0, 128.0, 125.4, 125.4, 125.4, 125.4, 125.1, 123.8, 114.7, 114.7, 105.1, 55.7; EI-MS:
m/z (rel. int. %): 409 (M+, 45), 203 (100), 191(21), 176 (26), 101 (15), 88 (25); MS: as
calculated 409.5029 and found 409.5020.
4.2.14.
(E)-4-((2-(4-(4-Methoxyphenyl)thiazol-2-yl)hydrazono)methyl)-N,N-
dimethylaniline (14)
1
Yield: 38%; Solid m.p. 264 °C; H-NMR: (DMSO-d6, 300 MHz): δ 7.9 (s, 1H, HC=N),
7.7 (d, J2,3/6,5 = 8.7 Hz , 2H, H-2/6), 7.4 (d, J2″,3″/6″,5″ = 8.7 Hz , 2H, H-2″/6″), 7.0 (s, 1H,
H-5′), 6.9 (d, J3,2/5,6 = 8.7 Hz , 2H, H-3/5), 6.7 (d, J3″,2″/5″,6″ = 9.6 Hz , 2H, H-3″/5″), 3.7
(s, 3H, OMe), 2.9 (s, 6H, 2Me); 13C NMR (75 MHz, DMSO-d6): 171.6, 160.5, 153.2,
150.1, 143.2, 128.4, 128.4, 128.1, 128.1, 125.2, 123.1, 114.7, 114.7, 111.7, 111.7, 105.1,
55.7, 41.0, 41.0; EI-MS: m/z (rel. int. %): 352 (M+, 100), 206(100), 191 (91), 164 (65),
147 (67); MS: as calculated 352.1358 and found 352.1350.
4.2.15.
(15)
(E)-4-(4-Methoxyphenyl)-2-(2-(naphthalen-2-yl-methylene)hydrazinyl)thiazole
Yield: 32%; Solid m.p. 291 °C; 1H-NMR: (DMSO-d6, 300 MHz): δ 12.2 (s, 1H, NH), 8.1
(s, 1H, HC=N), 8.0 (s, 1H, H-8), 7.9 (m, 4H, H-/3/4/5/8), 7.8 (d, J2″,3″/6″,5″ = 6.6 Hz , 2H,
H-2″/6″), 7.5 (m, 2H, H-6/7), 7.1 (s, 1H, H-5′), 6.9 (d, J3″,2″/5″,6″ = 6.6 Hz , 2H, H-3″/5″),
3.7 (s, 3H, OMe); EI-MS: m/z (rel. int. %): 359 (M+, 48), 206 (100), 191 (22), 164 (33),
153 (79); MS: as calculated 359.1092 and found 359.1099.
4.2.16. (E)-2-(2-(4-(Benzyloxy)benzylidene)hydrainyl)-4-(4-methoxyphenyl)thiazole (16)
1
Yield: 81%; Solid m.p. 310 °C; H-NMR: (DMSO-d6, 300 MHz): δ 7.9 (s, 1H, HC=N),
8.0 (d, J2,3/6,5 = 6.6 Hz , 2H, H-2/6), 7.5 (d, J2″′,3″′/6″′,5″′ = 6.3 Hz , 2H, H-2″′/6″′), 7.4 (d,
J2″,3″/6″,5″ = 5.4 Hz , 2H, H-2″/6″), 7.3 (m, 2H, H-3″′/5″′), 7.2 (t, J4″′/3″′,5″′ = 6 Hz, 1H, H-
4″′), 7.1 (s, 1H, H-5′), 7.0 (d, J3,2/5,6 = 6.6 Hz , 2H, H-3/5), 6.9 (d, J3″,2″/5″,6″ = 6.3 Hz , 2H,
11

13
H-3″/5″), 5.1 (s, 2H, OCH2), 3.7 (s, 3H, OMe); C NMR (75 MHz, DMSO-d6): 128.7,
127.5, 128.7, 127.0, 127.0, 136.5, 114.3, 161.2, 144.2, 70.5, 130.1, 126.0, 130.3, 143.1,
171.6, 128.4, 114.7, 105.1, 128.4, 114.7, 125.2, 150.1, 160.4, 55.6; EI-MS: m/z (rel. int.
%): 415 (M+, 10), 206 (88), 191 (17), 149 (18), 91 (100); MS: as calculated 415.1354
and found 415.1349.
4.2.17.
(E)-2,6-Di-tert-butyl-4-((2-(4-(4-Methoxyphenyl)thiazol-2-yl)hydrazono)-
methyl)phenol (17)
1
Yield: 99%; Solid m.p. 282 °C; H-NMR: (DMSO-d6, 300 MHz): δ 7.9 (s, 1H, HC=N),
7.7 (d, J2″,3″/6″,5″ = 6.3 Hz , 2H, H-2″/6″), 7.4 (s, 2H, H-2/6), 7.0 (s, 1H, H-5′), 6.9 (d,
13
J3″,2″/5″,6″ = 6.6 Hz , 2H, H-3″/5″), 3.7 (s, 3H, OMe), 1.3 (s, 18H, 6Me); C NMR (75
MHz, DMSO-d6): 171.6, 160.5, 156.8, 150.1, 143.2, 136.1, 136.1, 128.4, 128.4, 125.2,
125.4, 123.6, 123.6, 114.7, 114.7, 105.1, 55.8, 34.3, 34.3, 31.4, 31.4, 31.4, 31.4, 31.4,
31.4; EI-MS: m/z (rel. int. %): 437 (M+, 22), 261 (32), 206 (100), 191 (30), 164 (61); MS:
as calculated 437.2137 and found 437.2130.
4.2.18. 1-((E)-(2-(4-(4-Methoxyphenyl)thiazol-2-yl)hydrazono)methyl)-3-((Z)-(2-(4-(4-
methoxy phenyl)thiazol-2-yl)hydrazono)methyl)benzene (18)
1
Yield: 86%; Solid m.p. 279 °C; H-NMR: (DMSO-d6, 300 MHz): δ 11.5 (s, 2H, NH),
8.2 (s, 1H, H-2), 8.0 (s, 2H, 2xHC=N), 7.9 (s, 2H, 2xH-5′), 7.7 (d, J2″,3″/6″,5″ = 8.7 Hz ,
4H, 2xH-2″/6″), 7.6 (d, J4,5/6,5 = 7.5 Hz , 2H, H-4/6), 7.5 (m, 1H, H-5), 6.9 (d, J3″,2″/5″,6″
=
13
8.7 Hz , 4H, 2xH-3″/5″), 3.7 (s, 6H, 2-OMe); C NMR (75 MHz, DMSO-d6): 171.6,
171.6, 160.4, 160.4, 150.1, 150.1, 143.2, 143.2, 133.7, 133.7, 131.4, 131.1, 128.4, 128.4,
128.4, 128.4, 128.3, 128.3, 125.2, 125.2, 124.8, 124.6, 114.6, 114.6, 105.1, 105.1, 55.7,
55.7; ESI/MS; calculated for and found EI-MS: m/z (rel. int. %): 540 (M+, 59), 309 (66),
206 (100), 191 (42), 149 (46), 128 (37); MS: as calculated 540.1402 and found 540.1410.
4.2.19. 5-(4-methoxyphenyl)-2-((E)-2-(4-((E)-(2-(4-(4-methoxyphenyl)thiazol-2-
yl)hydrazono)methyl)benzylidene)hydrazinyl)thiazole (19)
Yield: 85%; Solid m.p. 284 °C; 1H-NMR: (DMSO-d6, 300 MHz): δ 11.5 (s, 1H, NH), 8.0
(s, 2H, 2xHC=N), 7.9 (s, 2H, 2xH-5′), 7.7 (d, J2″,3″/6″,5″ = 8.7 Hz , 4H, 2xH-2″/6″), 7.6 (d,
J 2,3/6,5 = 7.5 Hz , 2H, H-2/6), 7.6 (d, J3,2/5,6 = 7.5 Hz , 2H, H-3/5), 6.9 (d, J3″,2″/5″,6″ = 8.7
12

13
Hz , 4H, 2xH-3″/5″), 3.7 (s, 6H, 2OMe); C NMR (75 MHz, DMSO-d6): 171.6, 160.4,
160.4, 150.1, 150.1, 143.2, 143.2, 133.7, 133.7, 131.2, 131.2, 128.4, 128.4, 128.4, 128.4,
128.3, 128.3, 125.2, 125.2, 125.1, 125.1, 114.6, 114.6, 105.1, 105.1, 55.7, 55.7; EI-MS:
m/z (rel. int. %): 540 (M+, 29), 390 (54), 206 (100), 191 (37), 149 (35); MS: as calculated
540.1402 and found 540.1415.
4.2.20. (E)-2-Methoxy-5-((2-(4-(4-methoxyphenyl)thiazol-2- yl)hydrazono)methyl)-
phenol (20)
1
Yield: 52%; Solid m.p. 270 °C; H-NMR: (DMSO-d6, 300 MHz): δ 7.8 (s, 1H, HC=N),
7.7(d, J2″,3″/6″,5″ = 6.6 Hz , 2H, H-2″/6″), 7.2 (d, J2,6 = 0.9 Hz , 1H, H-2), 7.1 (s, 1H, H-5′),
13
6.9 (m, 4H, H-3″/5″/5/6), 3.7 (s, 6H, 2OMe); C NMR (75 MHz, DMSO-d6): 171.6,
160.4, 152.1, 150.0, 147.0, 143.1, 131.2, 128.2, 128.2, 125.1, 122.6, 115.8, 114.7, 114.7,
112.2, 105.1, 56.2, 55.7; EI-MS: m/z (rel. int. %): 355 (M+, 30), 206 (100), 191 (27), 164
(54), 149 (43); MS: as calculated 355.0991and found 355.0999.
4.2.21. (E)-4-((2-(4-(4-Methoxyphenyl)thiazol-2-yl)hydrazono)methyl)benzene-1,2-diol
(21)
1
Yield: 86%; Solid m.p. 287 °C; H-NMR: (DMSO-d6, 300 MHz): δ 7.8 (s, 1H, HC=N),
7.7 (d, J5,6 = 6.6 Hz , 1H, H-5), 7.2 (d, J6,5 = 6.6 Hz , 1H, H-6), 7.1(d, J2,6 = 1.5 Hz , 1H,
H-2), 7.0 (s, 1H, H-5′), 6.9 (d, J2″,3″/6″,5″ = 6.6 Hz , 2H, H-2″/6″), 6.7 (d, J3″,2″/5″,6″ = 6 Hz ,
13
2H, H-3″/5″), 3.7 (s, 3H, OMe); C NMR (75 MHz, DMSO-d6): 171.5, 150.1, 149.4,
146.0, 143.2, 133.1, 131.1, 129.1, 129.1, 128.6, 127.4, 127.4, 123.1, 117.2, 116.2, 105.1,
46.5; EI-MS: m/z (rel. int. %): 341 (M+, 30), 217 (100), 191 (27), 164 (54), 149 (43); MS:
as calculated 341.0834 and found 341.0823.
Acknowledgments
The authors are thankful to Higher Education Commission of Pakistan.
13

References
1.
A.J. Hirsh, S.Y. Yao, J.D. Young, C.I. Cheeseman, Gastroenterology, 113 (1997)
205.
2.
3.
4.
5.
J.B. Torrelles, A.K. Azad, L.S. Schlesinger, J. Immunol. 177 (2006) 1805.
E. Gallienne, T. Gefflaut, M. Lemaire, J. Org. Chem. 71 (2006) 894.
J. E. Groopman, Rev. Infect. Dis. 12 (1990) 908.
B. Brazdova, N.S. Tan, N.M. Samoshina, V. V. Samoshin, Carbohydr. Res. 344
(2009) 311.
6.
N. Zitzmann, A.S. Mehta, S. Carrouee, T.D. Butters, F.M. Platt, J. McCauley,
B.S. Blumberg, R.A. Dwek, T.M. Block, Proc. Natl. Acad. Sci. USA. 96 (1999)
11878.
7.
R.A. Dwek, T.D. Butters, F.M. Platt, N. Zitzmann, Nat. Rev. Drug Discov. 1
(2002) 65.
8.
G. Long, M. Westenberg, H. Wang, J.M. Vlak, Z. Hu, J. Gen. Virol. 87 (2006)
839.
9.
S. Nadanaka, H. Yoshida, F. Kano, M. Murata, K. Mori, Mol. Biol. Cell. 15
(2004) 253.
10.
11.
A. Goffard, N. Callens, B. Bartosch, C. Wychowski, F.L. Cosset, C. Montpellier,
J. Dubuisson, J. Virol. 79 (2005) 8400.
B.D. Walker, M. Kowalski, W.C. Goh, K. Kozarsky, M. Krieger, C. Rosen, L.
Rohrschneider, W.A. Haseltine, J. Sodroski, J. Pro. Natl. Acad. Sci. USA. 84
(1987) 8120.
12.
13.
H. Takahashi, S. Sou, R. Yamasaki, M. Sodeoka, Y. Hashimoto, Chem. Pharm.
Bull. 48 (2000) 1494.
S. Sou, S. Mayumi, H. Takahashi, R. Yamasaki, S. Kadoya, M. Sodeoka, Y.
Hashimoto, Bioorg. Med. Chem. Lett. 10 (2000) 1081.
L. J. Scott, C.M. Spencer, Drugs. 59 (2000) 521.
K.M. Khan F. Rahim, A. Wadood, N. Kosar, M. Taha, A. Khan, M. I. Fakhri, M.
Junaid, W. Rehman, M. Khan, S. Perveen, O. Abid, B. Mohammad, M. Sajid, M.
I. Choudhary, Eur J Med Chem. 81 (2014) 245.
14.
15.
16.
17.
A. D. Baron, Diabetes Res. Clin. Pr. 40 (1998) 51.
J.V. Metzger, The chemistry of heterocyclic compounds, in: Thiazole and Its
Derivatives, A Series of Monographs. 34 (1979). Wiley, Chichester.
J. Quiroga, P. Hernandez, B. Insuasty, R. Abonia, J. Cobo, A. Sanchez, M.
Nogueras, J. N. Low, J. Chem. Soc. Perkin Trans1. 4 (2002)555.
I. Hutchinson, S. A. Jennings, B. R. Vishnuvajjala, A. D. Westwell, M.F.G.
Stevens, J. Med. Chem. 45 (2002) 744.
K.M. Khan, F. Rahim, A. Wadood, N. Kosar, M. Taha, S. Lalani, A. Khan, M.I.
Fakhri, M. Junaid, W. Rehman, M. Khan, S. Perveen, M. Sajid, M.I. Choudhary,
Eur J Med Chem. 81 (2014) 245
18.
19.
20.
21.
22.
23.
S. Imran; M. Taha; N.H. Ismail; K. M. Khan; F. Naz; M. Hussain; S. Tauseef,
Molecules 19, 2014, 11722.
M. Taha, N.H. Ismail, S. Imran, K.M. Khan, 4-[5-(2-Methoxyphenyl)-1,3,4-
oxadiazol-2-yl]benzohydrazide. Molbank (2014) M826.
W. Jamil, S. Perveen, S.A.A. Shah, M. Taha, N.H. Ismail, S. Perveen, N.
Ambreen, K. M. Khan M.I. Choudhary, Molecules 19 (2014) 8788.
14

24.
25.
M. Taha, N.H. Ismail, W. Jamil, H. Rashwan, S.M. Kashif, A.A. Sain, M.I.
Adenan, E.H. Anouar, M. Ali, F. Rahim, K.M. Khan. Eur J Med Chem. 84 (2014)
731.
Z.S. Saify, A. Kamil, S. Akhtar, M. Taha, A. Khan, K.M. Khan, S. Jahan, F.
Rahim, S. Perveen, M.I. Choudhary, Med. Chem. Res., 23 (2014) 4447.
26.
27.
K.M. Khan, M. Khan, M. Saleem, M. Taha, S. Perveen, M.I. Choudhary, J. Pak.
Chem Soc. 35 (2013) 901.
M. Taha, N.H. Ismail, S. Lalani, M.Q. Fatmi, Atia-tul-Wahab, S. Siddiqui, K.M
Khan, S. Imran, M.I. Choudhary, Eur J. Med. Chem. 92 (2015) 387.
28.
29.
S. B. Ferreira, A.C.R. Sodero, M.F.C. Cardoso, E.S. Lima, C. R. Kaiser, F. P.
Silva, V. F. Ferreira, J. Med. Chem. 53 (2010) 2364.
a) F. Rahim, K. Ullah, H. Ullah, A. Wadood, M. Taha, A.U. Rehman, M. Ashraf,
A. Shaukat, W. Rehman, S. Hussain, K.M. Khan, Bioorg. Chem. 58 (2015) 81; b)
F. Rahim, F. Malik, H. Ullah, A. Wadood, F. Khan, M.T. Javid, M. Taha, W.
Rehman, A. Rehman, K.M. Khan. Bioorg. Chem. 2015, 60, 42-48; c) M. Taha,
N.H. Ismail, M.S. Baharudin, S. Lalani S. Mehboob, K.M. Khan, S. yousuf, S.
Siddiqui F. Rahim M.I. Choudhary. Med. Chem. Res. 24 (2015) 1310.
30.
L.R. Guerreiro, E.P. Carriero, L. Fernandes, T.A. Cardote, R. Moreira, A.T.
Caldeira, R. C. Guedes, A. J. Burke, Bioorg. Med. Chem. 21 (2013) 1911.
31.
32.
J. H. Park, S. Ko, H. Park, Bull. Korean Chem. Soc. 29 (2008) 921.
A. Roujeinikova, C. Raasch, S. Sedelnikova, W. Liebl, W. Rice, J. Mol. Biol. 321
(2002) 149.
33.
K. Yamamoto, H. Miyake, M. Kusunoki, S. Osaki, FEBS. J. 277 (2010) 4205.
15

Scheme, Table and Figures captions
Scheme-1; Synthesis of thiazole derivatives 1-21
Table-1; α-Glucosidase inhibitory potential of thiazole derivatives 1-21
Figure-1; The recognized binding modes and molecular interactions of the thiazole
analog 8 in the active site of α-glucosidase.
Figure-2: The recognized binding modes and molecular interactions of the control,
Acarbose in the active site of α-glucosidase.
.
Figure-3: The recognized binding modes and molecular interactions of thiazole analog
12 in the active site of α-glucosidase.
16

Scheme-1
17

Figure-1:
18

Figure-2:
19

Figure-3:
20

Table-1:
S. No.
R1
R2
R3
IC50 ± SEMa (µM)
219.85±1.12
H
4-Cl
1
2
3
CH3
H
4-Cl
4-Cl
43.26 ± 0.07
239.18±1.08
CH3
4-Cl
387.52±1.13
4
H
H
4-Cl
4-Cl
205.46±1.17
175.25±0.97
5
6
H
H
4-Cl
4-Cl
36.7 5±0.05
18.23±0.03
7
8
H
H
4-Cl
4-Cl
68.52±0.08
9
341.91±1.15
10
H
4-Cl
176.43±1.12
424.41±0.94
11
12
CH3
4-OMe
H
4-OMe
191.72±0.73
13
21

H
H
4-OMe
4-OMe
145.81±0.26
193.55±0.41
14
15
H
H
4-OMe
4-OMe
99.16±0.51
16
17
123.32±0.83
H
H
4-OMe
4-OMe
55.43±0.08
18
19
226.32±0.95
H
4-OMe
175.72±0.84
20
H
-
4-OMe
-
46.39±0.05
38.25±0.12
21
Acarbose
-
22

Graphical abstract
(IC50, 18.23 ± 0.03 μM)
Potent Inhibitors of α-glucosidase
23

Highlights:
Synthesis of Thiazole Derivatives
In vitro α-glucosidase inhibitory activity
Identification of a novel class of α-glucosidase inhibitors
Structure-activity Relationship established
Molecular docking
24