Synthesis, in vitro α-glucosidase inhibitory activity and molecular docking studies of novel benzothiazole-triazole derivatives

Article abstract of DOI:10.3390/molecules22091555

Benzothiazole-triazole derivatives 6a–6s have been synthesized and characterized by¹H-NMR and¹³C-NMR. All synthetic compounds were screened for their in vitro α-glucosidase inhibitory activity by using Baker’s yeast α-glucosidase enzyme. The majority of compounds exhibited a varying degree of α-glucosidase inhibitory activity with IC₅₀ values between 20.7 and 61.1 μM when compared with standard acarbose (IC₅₀ = 817.38 μM). Among the series, compound 6s (IC₅₀ = 20.7 μM) bearing a chlorine group at the 5-position of the benzothiazole ring and a tert-butyl group at the para position of the phenyl ring, was found to be the most active compound. Preliminary structure-activity relationships were established. Molecular docking studies were performed to predict the binding interaction of the compounds in the binding pocket of the enzyme.

Full text of DOI:10.3390/molecules22091555

molecules
Article
Synthesis, In Vitro α-Glucosidase Inhibitory Activity
and Molecular Docking Studies of Novel
Benzothiazole-Triazole Derivatives
Zipeng Gong 1,2,3, Yaping Peng 4, Jie Qiu 4, Anbai Cao 4, Guangcheng Wang 4,* and
Zhiyun Peng 4,
*
1
Provincial Key Laboratory of Pharmaceutics in Guizhou Province, Guizhou Medical University,
Beijing Road, Guiyang 550004, China; gzp4012607@126.com
2
3
4
School of Pharmacy, Guizhou Medical University, 4 Beijing Road, Guiyang 550004, China
National Engineering Research Center of Miao’s Medicines, 4 Beijing Road, Guiyang 550004, China
College of Chemistry and Chemical Engineering, Hunan Engineering Laboratory for Analyse and Drugs
Development of Ethnomedicine in Wuling Mountains, Jishou University, Jishou 416000, China;
yapingpeng17@163.com (Y.P.); qiujie_jsu@126.com (J.Q.); AnbaiCao1997@163.com (A.C.)
Correspondence: wanggch123@163.com or wanggch123@jsu.edu.cn (G.W.); pengzhiyun1986@163.com or
pzy2017@jsu.edu.cn (Z.P.); Tel.: +86-743-856-3911
*
Received: 29 August 2017; Accepted: 13 September 2017; Published: 15 September 2017
Abstract: Benzothiazole-triazole derivatives 6a
1H-NMR and 13C-NMR. All synthetic compounds were screened for their in vitro α-glucosidase
inhibitory activity by using Baker’s yeast -glucosidase enzyme. The majority of compounds
exhibited a varying degree of -glucosidase inhibitory activity with IC50 values between 20.7 and
61.1 M when compared with standard acarbose (IC50 = 817.38 M). Among the series, compound 6s
(IC50 = 20.7 M) bearing a chlorine group at the 5-position of the benzothiazole ring and a tert-butyl
–6s have been synthesized and characterized by
α
α
µ
µ
µ
group at the para position of the phenyl ring, was found to be the most active compound. Preliminary
structure-activity relationships were established. Molecular docking studies were performed to
predict the binding interaction of the compounds in the binding pocket of the enzyme.
Keywords: benzothiazole; triazole; α-glucosidase; molecular docking
1. Introduction
Type 2 diabetes is the most common type of diabetes, accounting for about 95 percent of diabetes
cases. It is characterized by high blood glucose (hyperglycemia), insulin resistance and relative
lack of insulin [
1
]. Hyperglycemia plays an important role in the development of type 2 diabetes
].
-D-glucose residues and releases free
and complications associated with diseases such as microvascular and macrovascular diseases [
2
α
α
-Glucosidase catalyzes the hydrolysis of terminal 1,4-linked
-D-glucose, which is to the main cause of hyperglycemia [
α
3]. Inhibition of α-glucosidase activity
is one of the important therapeutic approaches for the treatment of type 2 diabetes by slowing the
absorption process of glucose in intestine [ ]. Three inhibitors of -glucosidase enzyme (acarbose,
4
α
miglitol, and voglibose) are being clinically used for the management of type 2 diabetes, and these are
also used as anticancer [5], anti-HIV [6], and anti-hepatitis agents [7].
Benzothiazole is an important scaffold in bioorganic and medicinal chemistry, and has broad
applications in drug discovery and development [8]. Benzothiazole-based compounds exhibit
numerous biological activities such as anticonvulsant [
9], anti-inflammatory [10], antimicrobial [11],
anticancer [12] and anti-diabetic activities [13]. Some of benzothiazole-containing drugs, such as
riluzole (anticonvulsant), ethoxzolamide (glaucoma, ulcers and as a diuretic), and zopolrestat (diabetic
nephropathy and diabetes), have been used clinically for many years (Figure 1). Recently, M. Taha et al.
Molecules 2017, 22, 1555; doi:10.3390/molecules22091555
www.mdpi.com/journal/molecules

Molecules 2017, 22, 1555
2 of 11
reported the synthesis of a new class of benzothiazole hybrid with benzohydrazide moiety, and some
of these showed superior activity compared to standard acarbose [14].
Figure 1. The structures of some commercial drugs containing benzothiazole or 1,2,3-triazole moiety.
On the other hand, 1,2,3-triazoles are an important class of heterocyclic compounds, and have been
widely applied in various fields, including synthetic organic chemistry, biological science, material
science and medicinal chemistry [15,16]. Notably, 1,2,3-triazole derivatives have been reported to
exhibit various biological activities such as antioxidant [17], antibacterial [18], antitubercular [19] and
anticancer [20]. There are some clinical and commercial drugs, such as tazobactam, cefatrizine and
carboxyamidotriazole, with 1,2,3-triazole moiety (Figure 1). In particular, several recent studies have
shown that some 1,2,3-triazole derivatives exhibit α-glucosidase inhibitory activity [21–25].
In continuation of our drug discovery research on potential antidiabetic agents [25
we synthesized a novel series of benzothiazole-triazole derivatives and evaluated for their in vitro
-glucosidase inhibitory activity. Furthermore, molecular docking was also performed to predict the
–28],
α
binding interaction of the compounds in the binding pocket of the enzyme.
2. Results and Discussion
2.1. Chemistry
The synthesis of benzothiazole-triazole derivatives 6a
of various benzyl chlorides or benzyl bromides with NaN3 in DMF at room temperature for 24 h
provided the corresponding (azidomethyl)aryl . Treatment of substituted 2-aminobenzenethiol with
CS2 in the presence of KOH in reflux EtOH/H2O afforded substituted benzo[d]thiazole-2-thiol
which reacted with 3-bromoprop-1-yne to provide the key intermediate . In the final step, according
to Huisgen, the 1,3-dipolar cycloaddition reaction (click reaction), condensation of intermediate with
various (azidomethyl)aryl in the presence of sodium ascorbate and CuSO4 5H2O in DMF solution
resulted in the formation of the title products 6a–6s.
The structures of all the title compounds 6a
–6s is shown in Scheme 1. The reaction
1
2
4,
5
5
2
·
–
6s were characterized by 1H-NMR and 13C-NMR
1
spectra (Supplementary Materials). For instance, the H-NMR spectrum of 6a shows two singlet
signals at
NCH2, respectively. A doublet of two protons appeared at
to the aromatic protons of C2,6-H of the right phenyl ring. The benzothiazole protons appeared as two
doublets of one proton each at 7.86 and 7.99 ppm, and a triplet of one proton at 7.37 ppm with
a coupling constant of 8.0 Hz and 8.4 Hz, respectively. The rest of the protons of benzothiazole and
the right phenyl appeared as a multiplet of three protons between 7.45 and 7.51 ppm. The single
δ
4.68 ppm and
δ
5.55 ppm, which were assigned to the methylene protons of SCH2 and
δ
7.19 ppm (J = 8.4 Hz), which was assigned
δ
δ
δ
δ

Molecules 2017, 22, 1555
3 of 11
peak of the C-H of triazole ring was observed at
two characteristic peaks for methylene carbon at
δ
8.17 ppm. The 13C-NMR spectrum of 6a showed
27.9 ppm and δ 52.5 ppm. The remaining thirteen
δ
signals were assigned to benzothiazole, triazole and phenyl carbon in the compound 6a. Therefore, the
data of 1H-NMR and 13C-NMR is in agreement with the structure of compound 6a.
Scheme 1. (a) DMF, room temperature, 24 h; (b) KOH, EtOH/H2O, reflux, 12 h; (c) K2CO3, acetone,
reflux, 5 h; (d) sodium ascorbate, CuSO4·5H2O, DMF, r.t., 4 h.
2.2. α-Glucosidase Inhibition Assay
All the synthetic benzothiazole-triazole derivatives (6a
-glucosidase inhibitory activity by using Baker’s yeast
summarized in Table 1. The majority of compounds exhibited a varying degree of
inhibitory activity with IC50 values between 20.7 and 61.1 M when compared with standard acarbose
(IC50 = 817.38 M). Among the series, compounds 6a 6e 6i 6m 6n 6o and 6s displayed potent
–
6s) were screened to evaluate their in vitro
-glucosidase enzyme. The results are
-glucosidase
α
α
α
µ
µ
,
,
,
,
,
inhibitory activity with IC50 values of 28.7, 27.4, 29.4, 28.2, 28.0, 22.3 and 20.7 µM.
Table 1. α-Glucosidase inhibitory activity of novel benzothiazole-triazole derivatives (6a–6s).
Compound
R1
R2
IC50 (µM)
6a
6b
6c
6d
6e
6f
6g
6h
6i
6j
6k
6l
6m
6n
6o
6p
6q
6r
H
H
H
H
H
H
H
H
H
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
4-Br
2-Cl
2-Br
3-F
4-Cl
2-F
28.7
>100
37.4
61.1
27.4
>100
>100
41.0
29.4
45.9
48.4
33.6
28.2
28.0
22.3
38.6
53.1
44.4
20.7
817.38
H
3,5-Cl2
4-tBu
2-F
2-Br
2-Cl
4-Cl
4-Br
3,5-Cl2
3-F
4-F
H
4-tBu
6s
Acarbose

Molecules 2017, 22, 1555
4 of 11
2.3. Structure-Activity Relationship
The structure-activity relationship of this class of compounds has been summarized.
The introduction of electron withdrawing groups such as fluorine, chlorine, and bromine into the
phenyl ring results in an increase in inhibitory activity. Furthermore, shifting these groups from the
para to the ortho position decreased inhibitory activity. Introduction of the electron-withdrawing
group chlorine into the benzothiazole ring results in a significant increase in inhibitory activity. It
is interesting to point out that 6i and 6s containing the tert-butyl group at the para position of the
phenyl ring exhibited potent α-glucosidase inhibitory activity, with IC50 values of 29.4 and 20.7 µM,
respectively. In particular, compound 6s with a chlorine group at the 5-position of the benzothiazole
ring and a tert-butyl group at the para position of the phenyl ring, was found to be the most active
compound in this series. In order to illustrate the binding interactions of molecules into the active site
of α-glucosidase, molecular docking studies were conducted.
2.4. Molecular Docking
The theoretical binding mode between 6i and Saccharomyces cerevisiae
in Figure 2. Compound 6i adopted an “L-shaped” conformation in the pocket of the
α
-glucosidase is shown
-glucosidase.
α
The benzothiazole group of 6i was located at the hydrophobic pocket, surrounded by the residues
Phe-157, Phe-310 and Phe-311, while the 4-(tert-butyl)phenyl group of 6i stretched into the hydrophobic
pocket consisting of Phe-157, Phe-177 and Phe-300, forming a stable hydrophobic binding. Detailed
analysis showed that the triazole group in the middle of 6i formed CH-
Phe-300. In addition, cation- interactions were observed between 6i and the residues Lys-155, Arg-312
and Arg-439. Furthermore, 6i formed anion- interactions with the residues Glu-276 and Asp-349,
respectively. All these interactions helped 6i to anchor in the binding site of the α-glucosidase.
π interaction with the residue
π
π
Figure 2. Compound 6i was docked to the binding pocket of the Saccharomyces cerevisiae α-glucosidase.
To explain the activity order of 6i and 6s against
binding site of -glucosidase; the theoretical binding mode between 6s and
in Figure 3A. The interaction between 6s and -glucosidase was almost the same as the precursor
6i. The only difference was that the benzothiazole group of 6s formed stacking interactions
with the residues His-239 and Phe-157, which were not formed by 6i, making 6s more active than 6i
α
-glucosidase, 6s was then docked to the
α
α
-glucosidase is shown
α
π-π

Molecules 2017, 22, 1555
5 of 11
against
for 6i and
anti- -glucosidase assay. In summary, the above molecular simulations give us rational explanation of
the interactions between 6i 6s and -glucosidase, which provided valuable information for further
development of α-glucosidase inhibitors.
α
-glucosidase (Figure 3B). In addition, the estimated binding energies were
−
8.6 kcal
·
mol−1
−
8.9 kcal
·
mol−1 for 6s, respectively, which was consistent with the results of the in vitro
α
,
α
Figure 3.
(
A) Compound 6s was docked to the binding pocket of the Saccharomyces cerevisiae
α
-glucosidase; (
B) Compounds 6i and 6s were docked to the binding pocket of the Saccharomyces
cerevisiae α-glucosidase (overlapped).
3. Experimental Section
3.1. General
All starting materials and reagents were purchased from commercial suppliers. Nuclear magnetic
resonance spectra (NMR) were recorded on a Bruker spectrometer (400 MHz) with TMS as an external
reference and reported in parts per million.
3.2. General Procedure for the Synthesis of 2
A mixture of substituted benzyl chlorides or benzyl bromides
1 (1.0 mmol) and NaN3 (1.2 mmol)
in 10 mL DMF was stirred at room temperature for 24 h. After the completion of the reaction (monitored
by TLC), the mixture was poured into water and extracted 3 times for ethyl acetate. The combined
organic layers were dried over Na2SO4 and concentrated under vacuum. The residue was purified by
chromatography to give 2.
3.3. General Procedure for the Synthesis of 4
To a solution of substituted 2-aminobenzenethiol (2 mmol) in EtOH (20 mL) was added CS2
(4 mmol) and KOH (4 mmol), and the mixture was stirred at 80 ◦C for 12 h. After cooling to the room
temperature, the mixture was treated with ice-water (100 mL) and 10% HCl was added to adjust pH
to 2–3. The solid precipitate was collected by filtration to obtain
without further purification.
4, which was used in the next step
3.4. General Procedure for the Synthesis of 5
A mixture of
4 (1 mmol), 3-bromoprop-1-yne (1.5 mmol) and K2CO3 (3 mmol) in acetone (20 mL)
was stirred at reflux for 5 h. The solvent was evaporated under reduced pressure and the residue was
purified by chromatography to give 5.

Molecules 2017, 22, 1555
6 of 11
3.5. General Procedure for the Synthesis of Benzothiazole-Triazole Derivatives (6a–6s)
A mixture of
(0.10 g, 0.5 mmol) in DMF (10 mL) was stirred at room temperature for 4 h. After completion of
reaction, the content was poured into 50 mL ice cold water and extracted with ethylacetate (50 mL 3).
The combined organic extracts were dried over Na2SO4, filtered, and concentrated. The residue was
purified by chromatography on silica gel with EtOAc/petroleum ether to give the title products 6a 6s
5
(1.0 mmol),
2
(1.0 mmol), CuSO4
·
5H2O (0.025 g; 0.1 mmol) and sodium ascorbate
×
–
.
2-(((1-(4-Bromobenzyl)-1H-1,2,3-triazol-4-yl)methyl)thio)benzo[d]thiazole (6a). Yellow solid, yield 65%, m.p.
◦
1
112–114 C. H-NMR (d6-DMSO, 400 MHz)
J = 8.4 Hz, ArH), 7.37 (t, 1H, J = 8.4 Hz, ArH), 7.45–7.51 (m, 3H, ArH), 7.86 (d, 1H, J = 8.0 Hz, ArH),
7.99 (d, 1H, J = 8.0 Hz, ArH), 8.17 (s, 1H, CH-triazole); 13C-NMR (d6-DMSO, 100 MHz)
: 27.9, 52.5,
δ: 4.68 (s, 2H, SCH2), 5.55 (s, 2H, NCH2), 7.19 (d, 2H,
δ
121.7, 121.8, 122.3, 124.6, 125.0, 126.8, 130.5, 132.1, 135.2, 135.8, 143.2, 153.0, 166.1; MS (ESI, m/z): 416.96
[M + H]+.
2-(((1-(2-Chlorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)thio)benzo[d]thiazole (6b). Yellow solid, yield 79%,
m.p. 110–111 ◦C. 1H-NMR (d6-DMSO, 400 MHz)
δ: 4.69 (s, 2H, SCH2), 5.66 (s, 2H, NCH2), 7.11 (dd,
1H, J = 8.0 Hz, 1.2 Hz, ArH), 7.27 (dt, 1H, J = 8.0 Hz, 1.2 Hz, ArH), 7.33–7.39 (m, 2H, ArH), 7.45–7.49
(m, 2H, ArH), 7.86 (d, 1H, J = 8.0 Hz, ArH), 7.99 (d, 1H, J = 8.0 Hz, ArH), 8.15 (s, 1H, CH-triazole);
13C-NMR (d6-DMSO, 100 MHz)
δ: 27.9, 51.1, 121.7, 122.3, 125.0, 125.0, 126.8, 128.1, 130.0, 130.6, 130.7,
133.0, 133.7, 135.2, 143.0, 153.0, 166.1; MS (ESI, m/z): 373.03 [M + H]+.
2-(((1-(2-Bromobenzyl)-1H-1,2,3-triazol-4-yl)methyl)thio)benzo[d]thiazole (6c). Yellow solid, yield 52%, m.p.
104–106 ◦C. 1H-NMR (d6-DMSO, 400 MHz)
δ: 4.70 (s, 2H, SCH2), 5.64 (s, 2H, NCH2), 7.05 (dd, 1H,
J = 8.0 Hz, 1.2 Hz, ArH), 7.24–7.33 (m, 2H, ArH), 7.37 (dt, 1H, J = 8.0 Hz, 1.2 Hz, ArH), 7.47 (dt, 1H,
J = 8.0 Hz, 1.2 Hz, ArH), 7.62 (dd, 1H, J = 8.0 Hz, 1.2 Hz, ArH), 7.86 (d, 1H, J = 8.0 Hz, ArH), 7.99 (d,
1H, J = 8.0 Hz, ArH), 8.14 (s, 1H, CH-triazole); 13C-NMR (d6-DMSO, 100 MHz)
δ: 27.9, 53.4, 121.7,
122.3, 123.2, 125.0, 125.0, 126.8, 128.6, 130.7, 130.8, 133.3, 135.2, 135.3, 143.0, 153.0, 166.0; MS (ESI, m/z):
416.98 [M + H]+.
2-(((1-(3-Fluorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)thio)benzo[d]thiazole (6d). White solid, yield 67%, m.p.
◦
112–114 C. 1H-NMR (d6-DMSO, 400 MHz)
δ
: 4.69 (s, 2H, SCH2), 5.59 (s, 2H, NCH2), 7.06–7.16 (m, 3H,
ArH), 7.33–7.38 (m, 2H, ArH), 7.47 (dt, 1H, J = 8.0 Hz, 1.2 Hz, ArH), 7.87 (d, 1H, J = 8.0 Hz, ArH), 7.99
(d, 1H, J = 8.0 Hz, ArH), 8.22 (s, 1H, CH-triazole); 13C-NMR (d6-DMSO, 100 MHz)
: 27.9, 52.6, 115.1
δ
(d, 1C, J = 21.0 Hz), 115.3 (d, 1C, J = 21.0 Hz), 121.7, 122.3, 124.3 (d, 1C, J = 2.8 Hz), 124.7, 125.0, 126.8,
131.2 (d, 1C, J = 8.3 Hz), 135.2, 139.1 (d, 1C, J = 7.5 Hz), 143.2, 153.0, 161.3 (d, 1C, J = 243 Hz), 166.1; MS
(ESI, m/z): 357.06 [M + H]+.
2-(((1-(4-Chlorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)thio)benzo[d]thiazole (6e). White solid, yield 81%, m.p.
◦
1
119–120 C. H-NMR (d6-DMSO, 400 MHz) δ: 4.68 (s, 2H, SCH2), 5.57 (s, 2H, NCH2), 7.25 (d, 2H,
J = 8.4 Hz, ArH), 7.36 (d, 2H, J = 8.4 Hz, ArH), 7.40 (dd, 1H, J = 8.4 Hz, 2.0 Hz, ArH), 7.96 (d, 1H,
J = 2.0 Hz, ArH), 8.03 (d, 1H, J = 8.4 Hz, ArH), 8.20 (s, 1H, CH-triazole); 13C-NMR (d6-DMSO, 100
MHz) δ: 28.0, 52.5, 121.2, 123.7, 124.8, 125.0, 129.1, 130.2, 131.7, 133.3 134.0, 135.4, 143.0, 153.9, 169.0;
MS (ESI, m/z): 373.03 [M + H]+.
2-(((1-(2-Fluorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)thio)benzo[d]thiazole (6f). Yellow solid, yield 64%, m.p.
86–88 ◦C. 1H-NMR (d6-DMSO, 400 MHz)
δ: 4.69 (s, 2H, SCH2), 5.63 (s, 2H, NCH2), 7.12–7.28 (m, 3H,
ArH), 7.35–7.39 (m, 2H, ArH), 7.47 (dt, 1H, J = 8.0 Hz, 1.2 Hz, ArH), 7.86 (d, 1H, J = 8.0 Hz, ArH), 7.99
(d, 1H, J = 8.0 Hz, ArH), 8.16 (s, 1H, CH-triazole); 13C-NMR (d6-DMSO, 100 MHz) δ: 27.9, 47.3 (d, 1C,
J = 3.8 Hz), 115.9 (d, 1C, J = 20.8 Hz), 121.7, 122.3, 123.2 (d, 1C, J = 14.6 Hz), 124.7, 125.0, 125.2 (d, 1C,
J = 3.5 Hz), 126.8, 131.0 (d, 1C, J = 3.5 Hz), 131.1 (d, 1C, J = 8.2 Hz), 135.2, 143.1, 153.0, 159.3 (d, 1C,
J = 245 Hz), 166.1; MS (ESI, m/z): 357.06 [M + H]+.

Molecules 2017, 22, 1555
7 of 11
2-(((1-Be◦nzyl-1H-1,2,3-triazol-4-yl)methyl)thio)benzo[d]thiazole (6g) [29]. White solid, yield 72%, m.p.
109–110 C. 1H-NMR (d6-DMSO, 400 MHz)
δ: 4.68 (s, 2H, SCH2), 5.56 (s, 2H, NCH2), 7.23–7.25 (m, 2H,
ArH), 7.28–7.31 (m, 3H, ArH), 7.37 (dt, 1H, J = 8.0 Hz, 1.2 Hz, ArH), 7.47 (dt, 1H, J = 8.0 Hz, 1.2 Hz,
ArH), 7.87 (d, 1H, J = 8.0 Hz, ArH), 8.00 (d, 1H, J = 8.0 Hz, ArH), 8.18 (s, 1H, CH-triazole); 13C-NMR
(d6-DMSO, 100 MHz) δ: 27.9, 53.2, 121.7, 122.3, 124.6, 125.0, 126.8, 128.3, 128.5, 129.2, 135.2, 136.4, 143.1,
153.1, 166.1; MS (ESI, m/z): 339.07 [M + H]+.
2-(((1-(3,5-Dichlorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)thio)benzo[d]thiazole (6h). White solid, yield 75%,
m.p. 85–87 ◦C. 1H-NMR (d6-DMSO, 400 MHz)
δ: 4.69 (s, 2H, SCH2), 5.65 (s, 2H, NCH2), 7.15 (d, 1H,
J = 8.0 Hz, ArH), 7.35–7.39 (m, 2H, ArH), 7.47 (dt, 1H, J = 8.0 Hz, 1.2 Hz, ArH), 7.64 (d, 1H, J = 2.0 Hz,
ArH), 7.86 (d, 1H, J = 8.0 Hz, ArH), 8.00 (d, 1H, J = 8.0 Hz, ArH), 8.15 (s, 1H, CH-triazole); 13C-NMR
(d6-DMSO, 100 MHz) δ: 27.9, 50.5, 121.7, 122.3, 125.0, 126.8, 128.3, 129.6, 132.2, 132.8, 134.1, 134.4, 135.2,
143.1, 153.0, 166.0; MS (ESI, m/z): 406.99 [M + H]+.
2-(((1-(4-(Tert-butyl)benzyl)-1H-1,2,3-triazol-4-yl)methyl)thio)benzo[d]thiazole (6i). Yellow solid, yield 51%,
m.p. 77–78 ◦C. 1H-NMR (d6-DMSO, 400 MHz)
δ: 1.22 (s, 9H, CH3), 4.68 (s, 2H, SCH2), 5.51 (s, 2H,
NCH2), 7.15 (d, 2H, J = 8.4 Hz, ArH), 7.29 (d, 2H, J = 8.4 Hz, ArH), 7.37 (t, 1H, J = 8.0 Hz, ArH),
7.47 (t, 1H, J = 8.0 Hz, ArH), 7.87 (d, 1H, J = 8.0 Hz, ArH), 7.99 (d, 1H, J = 8.0 Hz, ArH), 8.16 (s, 1H,
CH-triazole); 13C-NMR (d6-DMSO, 100 MHz)
δ: 27.9, 31.5, 34.7, 53.0, 121.7, 122.3, 124.5, 125.0, 125.9,
126.8, 128.1, 133.5, 135.2, 143.1, 151.0, 153.1, 166.1; MS (ESI, m/z): 395.13 [M + H]+.
5-Chloro-2-(((1-(2-fluorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)thio)benzo[d]thiazole (6j). White solid, yield
◦
1
63%, m.p. 115–117 C. H-NMR (d6-DMSO, 400 MHz) δ: 4.68 (s, 2H, SCH2), 5.63 (s, 2H, NCH2),
7.12–7.27 (m, 3H, ArH), 7.35–7.40 (m, 1H, ArH), 7.40 (dd, 1H, J = 8.0 Hz, 2.0 Hz, ArH), 7.94 (d, 1H,
J = 2.0 Hz, ArH), 8.03 (d, 1H, J = 8.0 Hz, ArH), 8.17 (s, 1H, CH-triazole); 13C-NMR (d6-DMSO, 100 MHz)
δ
: 28.0, 47.3 (d, 1C, J = 3.9 Hz), 115.9 (d, 1C, J = 20.8 Hz), 121.2, 123.2 (d, 1C, J = 14.6 Hz), 123.7, 124.8,
125.0, 125.2 (d, 1C, J = 3.6 Hz), 131.0 (d, 1C, J = 3.5 Hz), 131.9 (d, 1C, J = 8.2 Hz), 131.6, 134.0, 142.9,
153.9, 159.2 (d, 1C, J = 245 Hz), 169.0; MS (ESI, m/z): 391.02 [M + H]+.
2-(((1-(2-Bromobenzyl)-1H-1,2,3-triazol-4-yl)methyl)thio)-5-chlorobenzo[d]thiazole (6k). White solid, yield
79%, m.p. 119–120 ◦C. 1H-NMR (d6-DMSO, 400 MHz)
δ: 4.69 (s, 2H, SCH2), 5.64 (s, 2H, NCH2), 7.05
(dd, 1H, J = 8.0 Hz, 2.0 Hz, ArH), 7.24–7.33 (m, 2H, ArH), 7.40 (dd, 1H, J = 8.0 Hz, 2.0 Hz, ArH), 7.61
(dd, 1H, J = 8.0 Hz, 1.2 Hz, ArH), 7.93 (d, 1H, J = 2.0 Hz, ArH), 8.02 (d, 1H, J = 8.8 Hz, ArH), 8.16 (s, 1H,
CH-triazole); 13C-NMR (d6-DMSO, 100 MHz)
δ: 28.0, 53.4, 121.2, 123.2, 123.7, 125.0, 125.2, 128.6, 130.7,
130.8, 131.6, 133.3, 134.0, 135.3, 142.8, 153.9, 168.9; MS (ESI, m/z): 450.93 [M + H]+.
5-Chloro-2-(((1-(2-chlorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)thio)benzo[d]thiazole (6l). White solid, yield
66%, m.p. 128–130 ◦C. 1H-NMR (d6-DMSO, 400 MHz)
δ: 4.69 (s, 2H, SCH2), 5.66 (s, 2H, NCH2), 7.11
(d, 1H, J = 8.0 Hz, ArH), 7.27 (t, 1H, J = 8.0 Hz, ArH), 7.36 (dt, 1H, J = 8.0 Hz, 2.0 Hz, ArH), 7.40 (dd,
1H, J = 8.8 Hz, 2.0 Hz, ArH), 7.45 (d, 1H, J = 8.0 Hz, ArH), 7.94 (d, 1H, J = 2.0 Hz, ArH), 8.03 (d, 1H,
J = 8.8 Hz, ArH), 8.16 (s, 1H, CH-triazole); 13C-NMR (d6-DMSO, 100 MHz)
δ: 28.0, 51.1, 121.2, 123.7,
125.0, 125.2, 128.1, 130.0, 130.6, 130.7, 131.6, 133.0, 133.7, 134.0, 142.8, 153.9, 168.9; MS (ESI, m/z): 406.99
[M + H]+.
5-Chloro-2-(((1-(4-chlorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)thio)benzo[d]thiazole (6m). White solid, yield
78%, m.p. 111–112 ◦C. 1H-NMR (d6-DMSO, 400 MHz)
δ: 4.68 (s, 2H, SCH2), 5.57 (s, 2H, NCH2), 7.25
(d, 2H, J = 8.0 Hz, ArH), 7.36 (d, 2H, J = 8.0 Hz, ArH), 7.40 (dd, 1H, J = 8.8 Hz, 2.0 Hz, ArH), 7.95
(d, 1H, J = 2.0 Hz, ArH), 8.02 (d, 1H, J = 8.4 Hz, ArH), 8.20 (s, 1H, CH-triazole); 13C-NMR (d6-DMSO,
100 MHz)
δ: 28.0, 52.4, 121.2, 123.7, 124.8, 125.0, 129.1, 130.2, 131.6, 133.3, 134.0, 135.4, 143.1, 153.9,
169.0; MS (ESI, m/z): 406.99 [M + H]+.

Molecules 2017, 22, 1555
8 of 11
2-(((1-(4-Bromobenzyl)-1H-1,2,3-triazol-4-yl)methyl)thio)-5-chlorobenzo[d]thiazole (6n). White solid, yield
73%, m.p. 114–116 ◦C. 1H-NMR (d6-DMSO, 400 MHz)
: 4.68 (s, 2H, SCH2), 5.55 (s, 2H, NCH2), 7.19
δ
(d, 2H, J = 8.4 Hz, ArH), 7.41 (dd, 1H, J = 8.4 Hz, 2.0 Hz, ArH), 7.49 (d, 2H, J = 8.4 Hz, ArH), 7.96
(d, 1H, J = 2.0 Hz, ArH), 8.03 (d, 1H, J = 8.4 Hz, ArH), 8.21 (s, 1H, CH-triazole); 13C-NMR (d6-DMSO,
100 MHz) δ: 28.0, 52.5, 121.2, 121.8, 123.7, 124.8, 125.0, 130.5, 131.6, 132.1, 134.0, 135.9, 1443.1, 153.9,
169.0; MS (ESI, m/z): 452.94 [M + H]+.
5-Chloro-2-(((1-(3,5-dichlorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)thio)benzo[d]thiazole (6o). Yellow solid,
yield 55%, m.p. 124–126 ◦C. 1H-NMR (d6-DMSO, 400 MHz)
δ: 4.69 (s, 2H, SCH2), 5.65 (s, 2H, NCH2),
7.15 (d, 1H, J = 8.4 Hz, ArH), 7.36 (dd, 1H, J = 8.4 Hz, 2.0 Hz, ArH), 7.41 (dd, 1H, J = 8.4 Hz, 2.0 Hz,
ArH), 7.63 (d, 1H, J = 2.0 Hz, ArH), 7.94 (d, 1H, J = 2.0 Hz, ArH), 8.03 (d, 1H, J = 8.4 Hz, ArH), 8.17 (s,
1H, CH-triazole); 13C-NMR (d6-DMSO, 100 MHz)
δ: 27.9, 50.5, 121.2, 123.7, 125.0, 125.2, 128.2, 129.5,
131.6, 132.1, 132.9, 134.0, 134.1, 134.4, 142.9, 153.9, 168.9; MS (ESI, m/z): 440.95 [M + H]+.
5-Chloro-2-(((1-(3-fluorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)thio)benzo[d]thiazole (6p). White solid, yield
◦
1
74%, m.p. 140–141 C. H-NMR (d6-DMSO, 400 MHz) δ: 4.68 (s, 2H, SCH2), 5.59 (s, 2H, NCH2),
7.06–7.14 (m, 3H, ArH), 7.34–7.36 (m, 1H, ArH), 7.40 (dd, 1H, J = 8.4 Hz, 2.0 Hz, ArH), 7.95 (d, 1H,
J = 2.0 Hz, ArH), 8.02 (d, 1H, J = 8.4 Hz, ArH), 8.23 (s, 1H, CH-triazole); 13C-NMR (d6-DMSO, 100 MHz)
δ
: 28.0, 52.6, 115.0 (d, 1C, J = 21.9 Hz), 115.3 (d, 1C, J = 20.8 Hz), 121.2, 123.7, 124.3 (d, 1C, J = 2.8 Hz),
124.9, 125.0, 131.2 (d, 1C, J = 5.3 Hz), 131.7, 134.0, 139.1 (d, 1C, J = 7.5 Hz), 143.1, 153.9, 161.3 (d, 1C,
J = 243 Hz), 169.0; MS (ESI, m/z): 391.02 [M + H]+.
5-Chloro-2-(((1-(4-fluorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)thio)benzo[d]thiazole (6q). Yellow solid, yield
68%, m.p. 108–109 ◦C. 1H-NMR (d6-DMSO, 400 MHz)
δ: 4.68 (s, 2H, SCH2), 5.55 (s, 2H, NCH2), 7.14
(d, 2H, J = 8.8 Hz, ArH), 7.31–7.34 (m, 2H, ArH), 7.41 (dd, 1H, J = 8.4 Hz, 2.0 Hz, ArH), 7.95 (d, 1H,
J = 2.0 Hz, ArH), 8.03 (d, 1H, J = 8.4 Hz, ArH), 8.19 (s, 1H, CH-triazole); 13C-NMR (d6-DMSO, 100 MHz)
δ
: 28.0, 52.5, 115.9 (d, 1C, J = 21.5 Hz), 121.2, 123.7, 124.6, 125.0, 130.6 (d, 1C, J = 8.3 Hz), 131.6, 132.7 (d,
1C, J = 3.1 Hz), 134.0, 143.0, 153.9, 161.1 (d, 1C, J = 243 Hz), 169.0; MS (ESI, m/z): 391.02 [M + H]+.
2-(((1-Benzyl-1H-1,2,3-triazol-4-yl)methyl)thio)-5-chlorobenzo[d]thiazole (6r) [29]. White solid, yield 75%,
m.p. 142–144 ◦C. 1H-NMR (d6-DMSO, 400 MHz)
δ: 4.68 (s, 2H, SCH2), 5.56 (s, 2H, NCH2), 7.25–7.30
(m, 5H, ArH), 7.41 (d, 1H, J = 8.4 Hz, ArH), 7.96 (d, 1H, J = 2.0 Hz, ArH), 8.03 (d, 1H, J = 8.4 Hz, ArH),
8.19 (s, 1H, CH-triazole); 13C-NMR (d6-DMSO, 100 MHz)
δ: 28.0, 53.3, 121.2, 123.7, 124.7, 125.0, 128.3,
128.5, 129.1, 131.6, 134.0, 136.4, 142.9, 153.9, 169.0; MS (ESI, m/z): 373.03 [M + H]+.
2-(((1-(4-(Tert-butyl)benzyl)-1H-1,2,3-triazol-4-yl)methyl)thio)-5-chlorobenzo[d]thiazole (6s). Yellow solid,
yield 78%, m.p. 94–95 ◦C. 1H-NMR (d6-DMSO, 400 MHz)
δ: 1.22 (s, 9H, CH3), 4.67 (s, 2H, SCH2), 5.51
(s, 2H, NCH2), 7.15 (d, 2H, J = 8.4 Hz, ArH), 7.28 (d, 2H, J = 8.4 Hz, ArH), 7.40 (d, 1H, J = 8.4 Hz,
ArH), 7.97 (d, 1H, J = 2.0 Hz, ArH), 8.03 (d, 1H, J = 8.4 Hz, ArH), 8.19 (s, 1H, CH-triazole); 13C-NMR
(d6-DMSO, 100 MHz) δ: 28.0, 31.5, 34.7, 53.0, 121.2, 123.7, 124.7, 125.0, 125.9, 128.0, 131.6, 133.5, 134.0,
142.9, 151.0, 153.9, 169.0; MS (ESI, m/z): 429.09 [M + H]+.
3.6. In Vitro Assay of α-Glucosidase Inhibitory Activity
α
-Glucosidase inhibitory activity was assayed by using 0.1 M phosphate buffer (pH 6.8) at 37 ◦C.
The enzyme (0.1 U/mL) in phosphate buffer saline was incubated with various concentrations of test
compounds at 37 ◦C for 15 min. Then 1.25 mM p-nitrophenyl
α-D-glucopyranoside was added to the
mixture as a substrate. After further incubation at 37 ◦C for 30 min. The absorbance was measured
spectrophotometrically at 405 nm. The sample solution was replaced by DMSO as a control. Acarbose
was used as a positive control.

Molecules 2017, 22, 1555
9 of 11
3.7. Molecular Docking
Molecular docking studies were performed to investigate the binding mode between 6i
,
6s and
α
-glucosidase using Autodock vina 1.1.2. The 3D structure of α-glucosidase of Saccharomyces cerevisiae
have been predicted using homology modeling in our previous report [25]. The 3D structure of the
compounds were obtained by ChemBioDraw Ultra 14.0 and ChemBio3D Ultra 14.0 softwares. The
AutoDockTools 1.5.6 package was employed to generate the docking input files. The search grid of
α
-glucosidase was identified as center_x:
−
19.676, center_y:
−
7.243, and center_z:
−
21.469, with
dimensions size_x: 15, size_y: 15, and size_z: 15. The value of exhaustiveness was set to 20. For
Vina docking, the default parameters were used if it was not mentioned. The best-scoring pose as
judged by the Vina docking score was chosen and visually analyzed using PyMoL 1.7.6 software
(http://www.pymol.org/).
4. Conclusions
In summary, a novel series of benzothiazole-triazole derivatives 6a
evaluated for their -glucosidase inhibitory activity. The majority of compounds exhibited superior
-glucosidase inhibitory activity in the range of IC50 = 20.7 and 61.1 M as compared to standard
acarbose (IC50 = 817.38 M). Molecular docking study was carried out to understand the molecular
interaction of compounds with the active site of -glucosidase. This study has identified a novel series
–6s have been synthesized and
α
α
µ
µ
α
of lead compounds which can be used for the development of new α-glucosidase inhibitors.
Supplementary Materials: Supplementary Materials are available online.
Acknowledgments: This work was supported by Key Technology R & D Program of Guizhou Province
([2017]2845); Natural Science Foundation of Jishou University (15JD004); Joint Foundation of Guizhou Province
Department of Science and Technology and Guizhou Medical University ([2016]7346); Jishou University for talent
introduction; The Open Project Program of Hunan Engineering Laboratory for Analyse and Drugs Development
of Ethnomedicine in Wuling Mountains.
Author Contributions: Guangcheng Wang designed and wrote the paper; Zipeng Gong, Yaping Peng,
Jie Qiu, Anbai Cao, and Zhiyun Peng carried out the experiments. All authors have read and approved the
final manuscript.
Conflicts of Interest: The authors confirm that this article content has no conflict of interest.
References
1.
2.
3.
4.
Ross, S.A.; Gulve, E.A.; Wang, M.H. Chemistry and biochemistry of type 2 diabetes. Chem. Rev. 2004, 104,
1255–1282. [CrossRef] [PubMed]
King, G.L.; Loeken, M.R. Hyperglycemia-induced oxidative stress in diabetic complications. Histochem. Cell
Biol. 2004, 122, 333–338. [CrossRef] [PubMed]
Hirsh, A.J.; Yao, S.Y.M.; Young, J.D.; Cheeseman, C.I. Inhibition of glucose absorption in the rat jejunum:
A novel action of alpha-D-glucosidase inhibitors. Gastroenterology 1997, 113, 205–211. [CrossRef]
Joshi, S.R.; Standl, E.; Tong, N.; Shah, P.; Kalra, S.; Rathod, R. Therapeutic potential of alpha-glucosidase
inhibitors in type 2 diabetes mellitus: An evidence-based review. Expert Opin. Pharmacother. 2015, 16,
1959–1981. [CrossRef] [PubMed]
5.
6.
7.
Pili, R.; Chang, J.; Partis, R.A.; Mueller, R.A.; Chrest, F.J.; Passaniti, A. The alpha-glucosidase I inhibitor
castanospermine alters endothelial cell glycosylation, prevents angiogenesis, and inhibits tumor growth.
Cancer Res. 1995, 55, 2920–2926. [PubMed]
Rawlings, A.J.; Lomas, H.; Pilling, A.W.; Lee, M.J.R.; Alonzi, D.S.; Rountree, J.S.S.; Jenkinson, S.F.; Fleet, G.W.J.;
Dwek, R.A.; Jones, J.H.; et al. Synthesis and Biological Characterisation of Novel N-Alkyl-Deoxynojirimycin
alpha-Glucosidase Inhibitors. ChemBioChem 2009, 10, 1101–1105. [CrossRef] [PubMed]
Zitzmann, N.; Mehta, A.S.; Carrouée, S.; Butters, T.D.; Platt, F.M.; McCauley, J.; Blumberg, B.S.; Dwek, R.A.;
Block, T.M. Imino sugars inhibit the formation and secretion of bovine viral diarrhea virus, a pestivirus
model of hepatitis C virus: Implications for the development of broad spectrum anti-hepatitis virus agents.
Proc. Natl. Acad. Sci. USA 1999, 96, 11878–11882. [CrossRef] [PubMed]

Molecules 2017, 22, 1555
10 of 11
8.
9.
Keri, R.S.; Patil, M.R.; Patil, S.A.; Budagumpi, S. A comprehensive review in current developments of
benzothiazole-based molecules in medicinal chemistry. Eur. J. Med. Chem. 2015, 89, 207–251. [CrossRef]
[PubMed]
Siddiqui, N.; Rana, A.; Khan, S.A.; Bhat, M.A.; Haque, S.E. Synthesis of benzothiazole semicarbazones as
novel anticonvulsants—The role of hydrophobic domain. Bioorg. Med. Chem. Lett. 2007, 17, 4178–4182.
[CrossRef] [PubMed]
10. Kharbanda, C.; Alam, M.S.; Hamid, H.; Javed, K.; Bano, S.; Dhulap, A.; Ali, Y.; Nazreen, S.;
Haider, S. Synthesis and evaluation of pyrazolines bearing benzothiazole as anti-inflammatory agents.
Bioorg. Med. Chem. 2014, 22, 5804–5812. [CrossRef] [PubMed]
11. Chugunova, E.; Boga, C.; Sazykin, I.; Cino, S.; Micheletti, G.; Mazzanti, A.; Sazykina, M.; Burilov, A.;
Khmelevtsova, L.; Kostina, N. Synthesis and antimicrobial activity of novel structural hybrids of
benzofuroxan and benzothiazole derivatives. Eur. J. Med. Chem. 2015, 93, 349–359. [CrossRef] [PubMed]
12. Gurdal, E.E.; Buclulgan, E.; Durmaz, I.; Cetin-Atalay, R.; Yarim, M. Synthesis and Anticancer Activity
Evaluation of Some Benzothiazole-Piperazine Derivatives. Anticancer Agents Med. Chem. 2015, 15, 382–389.
[CrossRef] [PubMed]
13. Puranik, N.V.; Puntambekar, H.M.; Srivastava, P. Antidiabetic potential and enzyme kinetics of benzothiazole
derivatives and their non-bonded interactions with alpha-glucosidase and alpha-amylase. Med. Chem. Res.
2016, 25, 805–816. [CrossRef]
14. Taha, M.; Ismail, N.H.; Lalani, S.; Fatmi, M.Q.; Atia-tul-Wahab; Siddiqui, S.; Khan, K.M.; Imran, S.;
Choudhary, M.I. Synthesis of novel inhibitors of alpha-glucosidase based on the benzothiazole skeleton
containing benzohydrazide moiety and their molecular docking studies. Eur. J. Med. Chem. 2015, 92, 387–400.
[CrossRef] [PubMed]
15. Agalave, S.G.; Maujan, S.R.; Pore, V.S. Click Chemistry: 1,2,3-Triazoles as Pharmacophores. Chem. Asian J.
2011, 6, 2696–2718. [CrossRef] [PubMed]
16. Hou, J.; Liu, X.; Shen, J.; Zhao, G.; Wang, P.G. The impact of click chemistry in medicinal chemistry.
Expert Opin. Drug Discov. 2012, 7, 489–501. [CrossRef] [PubMed]
17. Saraei, M.; Ghasemi, Z.; Dehghan, G.; Hormati, M.; Ojaghi, K. Synthesis of some novel 1,2,3-triazole
derivatives containing kojic acid moiety and evaluation for their antioxidant activity. Monatsh. Chem. 2017
148, 917–923. [CrossRef]
,
18. Thomas, K.D.; Adhikari, A.V.; Shetty, N.S. Design, synthesis and antimicrobial activities of some new
quinoline derivatives carrying 1,2,3-triazole moiety. Eur. J. Med. Chem. 2010, 45, 3803–3810. [CrossRef]
[PubMed]
19. Boechat, N.; Ferreira, V.F.; Ferreira, S.B.; Ferreira, M.D.L.G.; da Silva, F.D.C.; Bastos, M.M.; Costa, M.D.S.;
Lourenco, M.C.S.; Pinto, A.C.; Krettli, A.U.; et al. Novel 1,2,3-Triazole Derivatives for Use against
Mycobacterium tuberculosis H37Rv (ATCC 27294) Strain. J. Med. Chem. 2011, 54, 5988–5999. [CrossRef]
[PubMed]
20. Kamal, A.; Shankaraiah, N.; Devaiah, V.; Reddy, K.L.; Juvekar, A.; Sen, S.; Kurian, N.; Zingde, S. Synthesis of
1,2,3-triazole-linked pyrrolobenzodiazepine conjugates employing ‘click’ chemistry: DNA-binding affinity
and anticancer activity. Bioorg. Med. Chem. Lett. 2008, 18, 1468–1473. [CrossRef] [PubMed]
21. Chinthala, Y.; Domatti, A.K.; Sarfaraz, A.; Singh, S.P.; Arigari, N.K.; Gupta, N.; Satya, S.K.V.N.; Kumar, J.K.;
Khan, F.; Tiwari, A.K.; et al. Synthesis, biological evaluation and molecular modeling studies of some novel
thiazolidinediones with triazole ring. Eur. J. Med. Chem. 2013, 70, 308–314. [CrossRef] [PubMed]
22. Chinthala, Y.; Thakur, S.; Tirunagari, S.; Chinde, S.; Domatti, A.K.; Arigari, N.K.; Srinivas, K.V.N.S.; Alam, S.;
Jonnala, K.K.; Khan, F.; et al. Synthesis, docking and ADMET studies of novel chalcone triazoles for
anti-cancer and anti-diabetic activity. Eur. J. Med. Chem. 2015, 93, 564–573. [CrossRef] [PubMed]
23. Jabeen, F.; Shehzadi, S.A.; Fatmi, M.Q.; Shaheen, S.; Iqbal, L.; Afza, N.; Panda, S.S.; Ansari, F.L. Synthesis,
in vitro and computational studies of 1,4-disubstituted 1,2,3-triazoles as potential alpha-glucosidase
inhibitors. Bioorg. Med. Chem. Lett. 2016, 26, 1029–1038. [CrossRef] [PubMed]
24. Wang, G.; Peng, Z.; Wang, J.; Li, J.; Li, X. Synthesis and biological evaluation of novel
2,4,5-triarylimidazole-1,2,3-triazole derivatives via click chemistry as α-glucosidase inhibitors. Bioorg. Med.
Chem. Lett. 2016, 26, 5719–5723. [CrossRef] [PubMed]

Molecules 2017, 22, 1555
11 of 11
25. Wang, G.; Peng, Z.; Wang, J.; Li, X.; Li, J. Synthesis, in vitro evaluation and molecular docking studies of
novel triazine-triazole derivatives as potential
[CrossRef] [PubMed]
α-glucosidase inhibitors. Eur. J. Med. Chem. 2017, 125, 423–429.
26. Wang, G.; Wang, J.; He, D.; Li, X.; Li, J.; Peng, Z. Synthesis and biological evaluation of novel 1,2,4-triazine
derivatives bearing carbazole moiety as potent
2806–2809. [CrossRef] [PubMed]
α-glucosidase inhibitors. Bioorg. Med. Chem. Lett. 2016, 26,
27. Wang, G.; Chen, M.; Wang, J.; Peng, Y.; Li, L.; Xie, Z.; Deng, B.; Chen, S.; Li, W. Synthesis, biological evaluation
and molecular docking studies of chromone hydrazone derivatives as α-glucosidase inhibitors. Bioorg. Med.
Chem. Lett. 2017, 27, 2957–2961. [CrossRef] [PubMed]
28. Wang, G.; Peng, Z.; Wang, J.; Li, J.; Li, X. Synthesis, biological evaluation and molecular docking study of
N-arylbenzo[d]oxazol-2-amines as potential α-glucosidase inhibitors. Bioorg. Med. Chem. 2016, 24, 5374–5379.
[CrossRef] [PubMed]
29. Christou, S.; Edwards, A.C.; Pritchard, R.G.; Quayle, P.; Song, Y.; Stratford, I.J.; Williams, K.F.; Whitehead, R.C.
Synthesis of hybrid natural product analogues with anti-tumour properties. Tetrahedron 2016, 72, 5433–5443.
[CrossRef]
Sample Availability: Samples of the compounds 6a–6s are available from the authors.
©
2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access
article distributed under the terms and conditions of the Creative Commons Attribution
(CC BY) license (http://creativecommons.org/licenses/by/4.0/).