Synthesis of benzimidazole based hydrazones as non-sugar based α-glucosidase inhibitors: Structure activity relation and molecular docking

Article abstract of DOI:10.1002/ddr.21807

In search for α-glucosidase inhibitors used in the treatment of diabetes mellitus, a series of unique benzimidazole based hydrazones derivatives were synthesized (5a-5p), which were then investigated for their in vitro α-glucosidase inhibitory potential.

Full text of DOI:10.1002/ddr.21807

Received: 10 January 2021
DOI: 10.1002/ddr.21807
Revised: 9 February 2021
Accepted: 18 February 2021
R E S E A R C H A R T I C L E
Synthesis of benzimidazole based hydrazones as non-sugar
based α-glucosidase inhibitors: Structure activity relation
and molecular docking
Muhammad Umair Ahmad1 | Muhammad Rafiq1 | Bakhtawar Zahra1
|
Muhamamd Islam1,4 | Muhammad Ashraf2 | Mariya al-Rashida3 | Ajmal Khan5
Javid Hussain6 | Zahid Shafiq1 | Ahmed Al-Harrasi5
|
1Institute of Chemical Sciences, Bahauddin
Abstract
Zakariya University, Multan, Pakistan
2Department of Chemistry, The Islamia
In search for α-glucosidase inhibitors used in the treatment of diabetes mellitus, a
University of Bahawalpur, Bahawalpur, Pakistan
series of unique benzimidazole based hydrazones derivatives were synthesized
(5a-5p), which were then investigated for their in vitro α-glucosidase inhibitory
potential. The compounds of interest were characterized by modern spectroscopic
approaches including CHN, 1HNM R, 13CN MR and FTIR. The structure of compound
5n was distinctively authenticated through single crystal X-ray study. All compounds
depicted potent enzyme inhibitory potential with IC50 values in the range of 2.25
0.01 to 81.16 0.12 μM except 5n that showed IC50 value of 182.75 0.13 μM. A
limited structure–activity correlation demonstrated that substitutions of isatin, alde-
hydes and ketone in hydrazones moiety had remarkable contribution in the overall
activity and that was further supported by molecular docking studies carried out in
elucidating the mechanism of binding interaction of these compounds in the catalytic
site of α-glucosidase.
3Department of Chemistry, Forman Christian
College (A Chartered University), Ferozepur
Road, Lahore, Pakistan
4Jadeed Group of Companies, 53-C, Satellite
Town, Chandni Chowk, Murree Road,
Rawalpindi, Pakistan
5Natural and Medical Sciences Research
Center, University of Nizwa, Nizwa, Oman
6Department of Biological Sciences and
Chemistry, University of Nizwa, Nizwa, Oman
Correspondence
Zahid Shafiq, Institute of Chemical Sciences,
Bahauddin Zakariya University, Multan 60800,
Pakistan.
Email: zahidshafiq@bzu.edu.pk
Ajmal Khan and Ahmed Al-Harrasi, Natural and
Medical Sciences Research Center, University
of Nizwa, P.O. Box 33, Birkat Al Mauz, Nizwa
616, Sultanate of Oman.
K E Y W O R D S
benzimidazole based hydrazones, diabetes mellitus, molecular docking studies, X-ray
crystallography, α-glucosidase inhibitor
Email: ajmalchemist@yahoo.com and
aharrasi@unizwa.edu.om
1
|
INTRODUCTION
heterocyclic derivatives of hydrazones are reported for antiproliferative
(Melnyk et al., 2006; Samadhiya and Halve, 2001) and anticonvulsant
Hydrazones are basically a group of organic compounds having struc-
ture R1RC2 = NNH2. Ketones and aldehydes are related to hydrazones,
by simple substitution of the oxygen with the NNH2 functional group
and formed by reaction of hydrazine with aldehyde or ketones
(Dhainaut et al., 2000). Hydrazones are the well-known for their biolog-
ical activities and being the center of attention of medicinal chemists
(Raman et al., 2007; Sonawane et al., 2017). Hydrazones show a wide
range of biotic activities such as antimycotic (Panneerselvam
et al., 2009), anticancer (Chohan et al., 2006), antibacterial (Tarafder
et al., 2002), and herbicidal activities (Basser and Mote, 2001). The
activities (Taha et al., 2014). Acyl hydrazones also showed significant
biological activities, such as antimalarial (Melnyk et al., 2006), antiviral
(Tian et al., 2011), anticancer (Cui et al., 2010), anti-semitic (da Silva
et al., 2010), anticonvulsant (Dimmock et al., 2000), antidepressant
(Ergenç et al., 1998) and vasodilative activities (Zapata-Sudo
et al., 2010). Therefore, it has always been the major interest of medici-
nal as well as organic chemists to generate these heterocycles. Based
on the above facts, we synthesized a unique succession of hydrazones
derivatives and arbitrarily screened them for their retarding potential
against α-glucoside enzyme.
Drug Dev Res. 2021;1–11.
wileyonlinelibrary.com/journal/ddr
© 2021 Wiley Periodicals LLC.
1

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AHMAD ET AL.
In drug discovery process (Yoon et al., 2014), the imidazole and
α-glucosidase retardants may become the therapeutics of interest
(Hossain et al., 2020; Khanal and Patil, 2020; Mi et al., 2021;
Mohammadi et al., 2021; Xu et al., 2020).
benzimidazole nucleus, respectively, are key pharmacophores, as they
are frequently confronted in those drugs that depict a variety of phar-
macological activities including antiulcer (Torres et al., 2015), antihy-
pertensive (Zhu et al., 2016), antiviral (Pan et al., 2015), antifungal
(Patel et al., 2012), anticancer (Akhtar et al., 2017), anthelmintic
(Mavrova et al., 2006), antibacterial (Patel et al., 2012), cytotoxicity
(Akhtar et al., 2017), antimicrobial (Patel et al., 2012), anti-
inflammatory (Gaba et al., 2014), antitumor (Wu et al., 2016),
histamine-H3 antagonist (Venable et al., 2005), antioxidant (Sam
Daniel Prabu et al., 2019), gastro protective (Loriga et al., 1992), DNA
binding (Zhang et al., 2016), and Alzheimer disease (Gulcan
et al., 2019). In these days, one of the most well-known yet critical
metabolic disorder is diabetes mellitus (DM) affecting more than
400 million people (Khursheed et al., 2019), distinguished by inflated
blood-glucose levels along with variations in carbohydrate, lipid and
protein metabolism (Shobana et al., 2009). Currently the remedy uti-
lized against diabetes mellitus type 2 (DM T2) involves the suppres-
sion of postprandial hyperglycemia through lessening the ingestion of
gut glucose via inhibition of carbohydrate hydrolysing enzyme
(Bhandari et al., 2008). International Diabetes Federation performed
epidemiological research, which proclaimed that globally more than
375 million people had suffered from diabetes in 2012, and 4 out of
5 of them lived in under-developing countries. Complications of DM
include nephropathy, neuropathy, retinopathy, and a range of related
disorders (Padhi et al., 2020). In small intestine, the cleavage of oligo-
saccharides to glucose is catalyzed through α-glucosidase enzyme
(EC 3.2.1.20)). Its retardation can add power to the control over post-
prandial hyperglycemia and thus inhibits complications of diabetes
(Association, 2001). For treatment of diabetes, oral hypoglycemic
mediators like α-glucosidase are employed, but due to particular
mechanism of action they have their own restrictions. A couple of
instances of driving retardants, that is, miglitol as well as acarbose, are
commonly appeared to cause diarrhea and similar intestinal aggrava-
tion, along with bleating, abdominal pain, flatulence and cramping
(Carroll et al., 2003; Fonseca, 2003; Hanefeld, 1998; Lebovitz, 2002).
That's why, in controlling both kind of diabetes, alternative
Inspired by the various pharmacological of hydrazone and benz-
imidazole, and significance of α-glucosidase inhibition in diabetes
mellitus, the current work portrays the synthesis, characterization
along with α-glucosidase inhibition of some novel benzimidazole
based hydrazones derivatives.
2
|
RESULTS AND DISCUSSION
| Chemistry
2.1
Through the reaction series sketched out in Scheme 1, the formation
of hydrazones of interest (5a-p) was achieved. Later on, by oxidative
condensation of suitable aldehyde (2a-e) with sodium metabisulfite
and o-phenylenediamine, lH-benzimidazoles (3a-e) were generated
(Taha et al., 2014). For furnishing the N-derivatized esters, com-
pounds (3a-e) were treated with ethyl bromoacetate in DMSO/KOH,
which produced respective hydrazides (4a-e) on further treatment
with hydrazine hydrate under reflux in ethanol. To optimize the reac-
tion condition 3,4-dichloro phenyl hydrazide (4a) was reacted with
Isatin employing solvents with variable polarity, that is, EtOH, MeOH,
THE Dioxan and DCM, EtOH was found to be the solvent of choice
under reflux conditions. To broaden the scope of reaction and check
the compatibility of conditions towards various carbonyl compounds
with different substituents, derivatives of isatins, aldehydes and
ketone were used. The hydrazones of interest (5a-p) were acquired in
acceptable to fantastic yields (78–97%), by the condensation reaction
of corresponding hydrazides with various carbonyl compounds
(isatins, aldehydes and ketone). Spectral statistics, that is, IR, 1H NMR,
along with 13C NMR microanalysis (CHN) were used to establish the
assembly of new hydrazones. In IR the NH band emerged within the
range of 3209–3340 cm, whereas stretching of C=N appeared within
the range of 1593–1647, that appeared to be in congruence with the
genesis of newly formed azomethine C=N bond in hydrazones.
SCHEME 1 Synthesis of
compounds (5a-p)

AHMAD ET AL.
3
TABLE 1 Structures of different analogues of benzimidazole based hydrazones
Compounds
5a
R
X
3,4-Dichloro
5b
5c
5d
5e
5f
3,4-Dichloro
3,4-Dichloro
3,4-Dichloro
4-Isopropyl
4-Isopropyl
4-Isopropyl
4-Isopropyl
4-Isopropyl
5 g
5 h
5i
5j
3-Fluoro
3-Fluoro
3-Fluoro
3-Fluoro
5 k
5 l
5 m
(Continues)

4
AHMAD ET AL.
TABLE 1 (Continued)
Compounds
5n
R
X
3-Fluoro
5o
5p
3-Hydroxy-4-methoxy
3-Hydroxy-4-methoxy
TABLE 2 α-Glucosidase inhibitory activities of compounds 5a-5p.
Data is mean SEM, n = 3)
at 0.5 mM concentration. All compounds showed significant potent to
excellent inhibitory activity against the enzyme except 5n (Tables 1
and 2). Most compounds exhibited inhibition in the range of IC50
2.25 0.01 to 182.75 0.13 μM as compared with standard acarbose
(IC50 38.24 0.11 μM).
Compound
Inhibition (%) at 0.5 mM
97.13 0.12
97.45 0.15
98.24 0.12
98.52 0.11
97.36 0.22
95.24 0.43
97.53 0.18
94.23 0.15
98.75 0.12
91.25 0.18
92.56 0.19
89.56 0.17
92.13 0.18
89.34 0.18
94.51 0.26
96.52 0.12
42.12 0.18
92.31 0.14
IC50 (μM)
16.52 0.08
5a
5b
17.24 0.07
2.25 0.01
5c
5d
3.52 0.02
2.3
|
Structure–activity relationship
5e
32.51 0.08
65.27 0.09
65.24 0.11
65.53 0.11
16.24 0.07
62.45 0.11
75.28 0.14
81.16 0.12
64.73 0.13
182.75 0.13
71.52 0.13
21.52 0.07
5f
For all the synthetic compounds, a limited structure–activity relation-
ship was established. Apparently, their activities may be due the sub-
stitution of X group, which are isatin, aldehydes and ketone. To
confirm the main pharmacophore responsible for the activity, the
unsubstituted compound 4b was also checked for α-glucosidase inhi-
bition and was found inactive (Table 2). The compounds 4a-4d have
same R substitution of 3,4 dichloro, while different X group substitu-
tion having numerical data of IC50 in the range of 2.25 0.01 to
17.24 0.07 μM. The compound 5c appeared to be the most opera-
tive compound of the succession having IC50 value of 2.25 0.01 μM
even 16 times better than standard acarbose (IC50 38.24 0.11 μM).
The inhibitory activity of this may be due to the indol ring with nitro
substitution. The compound 5d also showed significant activity (IC50
3.52 0.02 μM) having coumarin moiety at X position. The com-
pounds 5b and 5c showed two times better activity than standard
acarbose having indole and fluoro indole group at X position, respec-
tively. The compounds 5e- 5i have 4-isopropyl group at R positions
with different X substitution and also showed potent inhibitory activ-
ity with IC50 values from 16.24 0.07 to 65.53 0.11 μM. The com-
pound 5i have dichloro benzene substitution at X position showed
IC50 value of 16.24 0.07 μM. These results showed that dichloro
benzene substitution enhanced the inhibitory activity of these com-
pounds observed in compounds 4a-4d. The activity further decreased
in case of single chloro benzene substitution as observed in compound
5 h. The compounds 5j-5n demonstrated excellent to moderate inhibi-
tory activity with IC50 values from 62.45 0.11 to 182.75 0.13 μM, as
5 g
5 h
5i
5j
5 k
5 l
5 m
5n
5o
5p
4b
> 500
38.24 0.11
Acarbose
The NH signal in 1H NMR was detected in series between
δ12.07–12.91 ppm while isatin NH appeared from δ11.25–11.89 Along
with these, the structure of targeted compounds have also been favored
by signals assigned to aromatic protons. The accurate mass of the
hydrazones (5a-e) was authenticated through mass spectrometry.
2.2
|
α-Glucosidase inhibitory activity
The synthesized benzimidazole based hydrazones derivatives were
subjected to in vitro screening against the yeast α-glucosidase enzyme

AHMAD ET AL.
5
FIGURE 1 Overlapping of
docked conformations of acarbose
(pink) with compound 5c (yellow)
and 5d (purple)
they have same 3-fluoro group at R position with various X substitutions.
It is noted that the weak inhibitor 5n (IC50 182.75 0.13 μM) of the
series have also fluoro substituted benzene at X position and 3-fluoro
group at R position. The result of 5j-5n showed that fluoro substituted
group decreased the activities of these compounds, which further con-
firmed from results of compound 5n. The compounds 5o and 5p have
3-hydroxy-4-methoxy at R position with fluoro and nitro indole
ring at X position, respectively. Again the nitro indole substituted
compound (5p) showed significant inhibition with IC50 value of
21.52 0.07 μM.
between this amino acid and most active compound 5c that may be
responsible for the observed inhibition. A hydrogen bonded interac-
tion with this amino acid Glu276, was also observed with acarbose. A
number of hydrophobic interactions were also observed with sur-
rounding amino acid residues (Figure 2).
For comparison, the molecular docking studies of second most active
inhibitor, compound 5d, were also carried out. The hydrogen bonding
was observed between the NH of amide group and Pro309 (2.53 Å).
Other non-bonded interactions were observed with Glu304, His239,
His279, Ser308, Asn 241 (Figure 3). Compared to the binding of com-
pound 5c, which was found to bind deep in the active site cavity, com-
pound 5d was found to bind near the entrance of active site (Figure 2).
2.4
|
Molecular docking
Molecular docking studies were carried out against the homology
built structure of α-glucosidase from Saccharomyces cerevisiae, as its
crystal structure is not yet available from the Protein Data Bank
(PDB). The homology model was assembled as well as authenticated
on behalf of our already accounted method (Chaudhry et al., 2017),
whereby oligo-1,6-glucosidase (PDB lD: 3A4A) from Saccharomyces
cerevisiae was employed as a model compound. Oligo-1,6-glucosidase
parts 72% character and 55% comparability with α-glucosidase suc-
cession [42]. Moreover, molecular docking of standard acarbose
was performed and its most favorable docked pose was compared
to that of compounds 5c and 5d, the two most active inhibitors.
Figure 1 shows overlap of docked conformations of acarbose (pink)
with compound 5c (yellow) and 5d (purple). These compounds
docked to the exact region of the active site where acarbose
docked (Figure 1).
3
|
CONCLUSION
In conclusion, in search of non-sugar based α-glucosidase inhibitors, a
series of novel benzimidazole based hydrazones derivatives (5a-5p) were
designed and synthesized. The structure–activity relationship of this
series showed that X group substitutions at hydrazone moiety is respon-
sible for inhibition of α-glucosidase enzyme. Further studies on the struc-
tural optimization of these derivatives are underway in our laboratory.
4
|
MATERIALS AND METHODS
All the starting materials and solvents were purchased from Sigma-
Aldric or Oakwood Chemicals and used without purification. The thin
layer chromatography (TLC) glazed by silica gel 60 aluminium-backed
plates 0.063–0.200 mm with appropriate solvent systems (Ethyl acetate:
Pet. Ether 1:3) as eluent to monitor the course of reactions. The UV light
with 254 nm was used to envisage the TLC spots. The infrared spectra
IR (KBr discs) were recorded in the range 4000–500 cm−1 via Bruker
Vector-22 spectrometer. 1H NMR spectra were recorded via Bruker
spectrometer 300, 400 MHz as dilute solutions in DMSO-d6 as deuter-
ated solvent at 25 ꢀC. The chemical shifts were recorded on the δ-scale
(ppm) by means of residual solvents as an internal standard (DMSO; 1H
Two most active inhibitors, compounds 5c and 5d were selected
for molecular docking studies. Figure 1 shows 3D and 2D interactions
of the most probable docked conformation of compound 5c. The nitro
group was found to act as a hydrogen bond acceptor towards amino
acid Gln181. Another hydrogen bond interaction was observed
between the ring nitrogen of imidazole ring and Glu276 (2.13 Å). It is
important to note here that Glu276 is the amino acid that is directly
involved in the catalysis process, hydrogen bonded interaction

6
AHMAD ET AL.
FIGURE 2 Binding site
interactions of compound 5c
FIGURE 3 Binding site
interactions of compound 5d
2.50). The J values were calculated in Hertz (Hz) and multiplicities were
assigned as s (singlet), d (doublet), t (triplet), q (quartet), quint (quintet)
and the prefixes br (broad) were used. CHN analysis were carried out on
Organic Elemental Analyzer by PerkinElmer. Melting points of synthe-
sized compounds were determined by means of a Gallen-Kemp melting
point apparatus and are uncorrected.
completion of the reaction as indicated by TLC, the reaction mixture
was poured into ice-cold water. The benzimidazole derivative (3a-e)
precipitated out which was filtered, washed three times with water
and then dried under vacuum. KOH pellets (2 g) were added in DMSO
(20 ml) and the mixture was stirred for 15 minutes followed by the
addition of benzimidazole derivative (5 mmol). To the stirred solution,
ethylchloroacetate (5 mmol) was added and stirring was continued for
further 2 hrs. The solution cooled briefly and after completion of the
reaction as indicated by TLC (Ethyl acetate: Pet. Ether 1:2), the reac-
tion was quenched by addition of diethyl ether (30 ml) and extracted
by addition of water (30 ml). The extraction was repeated three times
and the resultant ether layer was dried over Na2SO4 to obtain N-
ethylacetate derivatives. For hydrazide formation, the solution of
benzimidazole ester (9 mmol) and hydrazine hydrate (9 mmol) were
dissolved in ethanol and heated under reflux for 15 minutes. On
cooling the crystalline product was obtained which was filtered,
washer three times with cold ethanol and dried under vacuum to
obtain the benzimidazole hydrazides (4a-e) The products were further
purified by recrystallization in ethanol /dioxane.
5
|
SYNTHESIS OF BENZIMIDAZOLE
BASED HYDRAZONES (5A-P)
An appropriate aldehyde 2a-e (12 mmol) and sodium metabisulfite
(Na2S2O5, 6 mmol) were dissolved in 20 ml of aqueous ethanol (80%)
and the resultant mixture was stirred at room temperature for
30 minutes. Additional 20 ml of ethanol was added to the reaction
mixture and kept in ice bath for 4 hrs. The precipitates of adduct were
filtered and washed three times with ethanol and then dried under
vacuum. The mixture of adduct (6 mmol) and o-phenylenediamine
1 (6 mmol) were dissolved in DMF and the resultant solution was
heated at 130 ꢀC for 5 hrs. The course of the reaction was monitored
through TLC under UV lamp (Ethyl acetate: Pet. Ether 1:3) and after
In order to synthesize the hydrazine derivatives classical conden-
sation method was adopted. Briefly, the appropriate benzimidazole

AHMAD ET AL.
7
hydrazide (4a-e, 2 mmol) and corresponding carbonyl compound
(isatin/ketone/aldehyde, 2 mmol) were dissolved in ethanol
(10 ml) and stirred under reflux for 2–3 hrs. On completion of the
reaction, as monitored by TLC (Ethyl acetate: Pet. Ether 1:3), the
precipitates formed were filtered on cooling, washed thrice with
hot methanol and diethyl ether and dried under vacuum to fur-
nish the hydrazone derivatives (5a-p) in good to excellent
yields (79–96%).
130.87, 131.01, 131.98, 132.81, 136.44, 139.54, 142.67, 149.02,
151.12, 157.98, 159.56, 163.85; Anal calcd for C23H14Cl2N6O4
(508.05); C, 54.24; H, 2.77; N, 16.50; Found C, 54.31; H,
2.89; N, 14.61.
5.4
|
(E)-2-(2-(3,4-dichlorophenyl)-1H-benzo[d]
imidazol-1-yl)-N0-([4-oxo-4H-chromen-3-yl]methylene)
acetohydrazide (5d)
5.1
|
(E)-2-(2-[3,4-dichlorophenyl]-1H-benzo[d]
White cream solid; Yield 96%, m.p. 242-243ꢀC; IR (KBR) ʋ (cm−1):
3278 (NH), 1625 (C=N), 1666 (CONH), 1H-NMR (DMSO-d6) δ ppm;
5.77 (s, 2H, N-CH2-CO), 7.25–7.32 (m, 3H), 7.51–7.60 (m, 3H), 7.68
(dd, 1H, J = 8.22, 1.4 Hz), 7.88 (d, 1H, J = 1.32 Hz), 8.01 (dd, 1H,
J = 8.7, 1.1 Hz), 8.10 (dd, 1H, J = 8.12, 1.2 Hz), 8.21 (m, 1H), 8.72 (s,
1H, CH=N), 8.93 (s, 1H, CH-O), 12.28 (bs, 1H, NH); 13C NMR δ ppm;
108.24, 109.56, 111.76, 112.09, 117.17, 118.23, 119.65, 122.77,
123.02, 129.11, 130.88, 131.80, 132.16, 132.63, 133.23, 136.77,
140.12, 142.45, 149.98, 150.14, 154.99, 157.60, 160.11, 163.67,
168.77; Anal calcd for C25H16Cl2N4O3 (490.06); C, 61.11; H, 3.28; N,
11.40; Found C, 61.17; H, 3.31; N, 11.37.
imidazol-1-yl)-N0-(2-oxoindolin-3-ylidene)
acetohydrazide (5a)
Yellow solid; Yield 80%, m.p. 213-214ꢀC; IR (KBR) ʋ (cm−1): 3209
(NH), 1605 (C=N), 1645 (CONH), 1H-NMR (DMSO-d6) δ ppm; 5.75 (s,
2H, N-CH2-CO), 6.92–7.15 (m, 3H), 7.29 (t,1H, J = 7.91, 8.4 Hz),
7.31–7.40 (m, 3H), 7.47 (s, 1H), 7.61 (d, 1H, J = 7.45 Hz), 7.79 (d, 1H,
J = 7.23 Hz), 7.80 (d, 1H, J = 8.14 Hz), 11.25 (bs, 1H, NH), 12.56 (bs,
1H, NH); 13C NMR δ ppm; 106.0, 108.45, 110.44, 112.82, 118.01,
118.44, 119.34, 122.88, 123.56, 128.53, 130.13, 130.91, 131.01,
131.52, 132.62, 136.21, 139.65, 142.33, 149.16, 151.39, 157.96,
159.53, 162.91; Anal calcd for C23H15Cl2N5O2 (463.06); C, 59.50; H,
3.26; N, 15.08; Found C, 59.54; H, 3.31; N, 15.05.
5.5
|
(E)-N0-(5-fluoro-2-oxoindolin-3-ylidene)-
2-(2-(4-isopropylphenyl)-1H-benzo[d]imidazol-1-yl)
acetohydrazide (5e)
5.2
|
(E)-2-(2-(3,4-dichlorophenyl)-1H-benzo[d]
imidazol-1-yl)-N0-(5-fluoro-2-oxoindolin-3-ylidene)
acetohydrazide (5b)
Light brown solid; Yield 81%, m.p. 273-275ꢀC; IR (KBR) ʋ (cm−1):
3304 (NH), 1626 (C=N), 1687 (CONH), 1H-NMR (DMSO-d6) δ ppm;
1.21 (d, 6H, 2xCH3), 2.92–2.96 (m, 1H, -CH), 5.73 (s, 2H, N-CH2-CO),
6.95–6.98 (m, 1H), 7.13 (dd, 2H, J = 8.01, 1.4 Hz), 7.22–7.27 (m, 1H),
7.32–7.41 (m, 3H), 7.43 (d, 1H, J = 1.2 Hz), 7.48–7.53 (m, 2H), 7.72 (d,
1H, J = 8.13 Hz), 7.71–7.80 (dd, 2H, J = 8.11, 1.3 Hz), 11.81 (bs, 1H,
NH), 12.56 (bs, 1H, NH); 13C NMR δ ppm; 18.56, 41.11, 108.16,
109.02, 111.45, 112.12, 118.23, 118.43, 119.77, 122.28, 123.87,
129.12, 130.46, 131.28, 132.78, 136.55, 139.59, 142.11, 149.54,
Light yellow solid; Yield 92%, m.p. 209-211ꢀC; IR (KBR) ʋ (cm−1): 3314
(NH), 1626 (C=N), 1653 (CONH), 1H-NMR (DMSO-d6) δ ppm; 5.73 (s,
2H, N-CH2-CO), 6.95 (s, 1H), 7.23 (t,1H, J = 7.86, 8.4 Hz), 7.28–7.33 (m,
2H), 7.37 (s, 1H), 7.65 (d, 1H, J = 7.26 Hz), 7.68 (d, 1H, J = 7.08 Hz), 7.81
(d, 1H, J = 8.34 Hz), 7.99 (s, 1H), 11.31 (bs, 1H, NH), 12.63 (bs, 1H, NH);
13C NMR δ ppm; 108.1, 108.26, 111.01, 112.45, 118.28, 118.44, 119.42,
122.63, 123.24, 128.97, 130.59, 130.87, 131.21, 131.72, 132.84, 136.57,
139.00, 142.35, 149.09, 151.22, 157.55, 159.13, 162.54; Anal calcd for
151.29, 157.26, 159.62, 163.98; Anal calcd for
C26H22FN5O2
(455.18); C, 68.56; H, 4.87; N, 15.38; Found C, 68.59; H,
4.81; N, 15.43.
C23H14Cl2FN5O2 (481.05); C, 57.28; H, 2.93; N, 14.52; Found C,
57.35; H, 2.99; N, 14.63.
5.6
|
(E)-2-(2-(4-isopropylphenyl)-1H-benzo[d]
5.3
|
(E)-2-(2-(3,4-dichlorophenyl)-1H-benzo[d]
imidazol-1-yl)-N0-(5-nitro-2-oxoindolin-3-ylidene)
acetohydrazide (5f)
imidazol-1-yl)-N0-(5-nitro-2-oxoindolin-3-ylidene)
acetohydrazide (5c)
Light brown solid; Yield 81%, m.p. 234-236ꢀC; IR (KBR) ʋ (cm−1):
3350 (NH), 1641 (C=N), 1681 (CONH), 1H-NMR (DMSO-d6) δ ppm;
1.22 (d, 6H, 2xCH3), 2.93–2.97 (m, 1H, -CH), 5.71 (s, 2H, N-CH2-CO),
7.32–7.41 (m, 3H), 7.49–7.57 (m, 3H), 7.71 (d, 1H, J = 8.21 Hz),
7.72–7.81 (m, 2H), 8.03 (s, 1H), 8.26–8.33 (m, 2H), 11.89 (bs, 1H,
NH), 12.53 (bs, 1H, NH); 13C NMR δ ppm; 18.32, 41.02, 108.46,
108.98, 111.34, 112.34, 118.01, 118.97, 119.65, 122.87, 123.76,
129.44, 130.87, 131.98, 132.52, 136.78, 139.11, 142.76, 149.11,
Light yellow solid; Yield 81%, m.p. 223-224ꢀC; IR (KBR) ʋ (cm−1):
3340 (NH), 1618 (C=N), 1678 (CONH), 1H-NMR (DMSO-d6) δ ppm;
5.82 (s, 2H, N-CH2-CO), 7.03–7.15 (m, 1H), 7.23–7.32 (m,2H), 7.65
(d, 1H, J = 7.44 Hz), 7.69–7.74 (ddd, 2H, J = 7.44, 1.4 Hz), 7.81 (d,
1H, J = 8.22 Hz), 8.00 (s, 1H), 8.26–8.31 (m, 2H), 11.85 (bs, 1H,
NH), 12.49 (bs, 1H, NH); 13C NMR δ ppm; 108.32, 108.87, 111.21,
112.51, 118.18, 118.35, 119.40, 122.91, 123.24, 129.11, 130.78,

8
AHMAD ET AL.
151.78, 157.88, 159.14, 163.76; Anal calcd for C26H22N6O4
(482.17); C, 64.72; H, 4.60; N, 17.42; Found C, 64.78; H,
4.63; N, 17.40.
(464.12); C, 64.52; H, 4.76; N, 12.04; Found C, 64.61; H,
4.88; N, 12.01.
5.10
|
(E)-2-(2-[3-fluorophenyl]-1H-benzo[d]
5.7
|
(E)-N0-(5-chloro-2-oxoindolin-3-ylidene)-
imidazol-1-yl)-N0-(5-methyl-2-oxoindolin-3-ylidene)
acetohydrazide (5j)
2-(2-(4-isopropylphenyl)-1H-benzo[d]imidazol-1-yl)
acetohydrazide (5 g)
Light orange solid; Yield 91%, m.p. 204-205ꢀC; IR (KBR) ʋ (cm−1):
3269 (NH), 1623 (C=N), 1684 (CONH), 1H-NMR (DMSO-d6) δ ppm;
2.21 (s, 3H, CH3), 5.78 (s, 2H, N-CH2-CO), 7.02 (dd, 1H, J = 1.32 Hz),
7.17–7.28 (m, 2H), 7.49 (dd, 1H, J = 8.26, 1.21 Hz), 7.55 (dd, 1H,
J = 7.89, 1.32 Hz), 7.61–7.68 (m, 2H), 7.71 (dd, 1H, J = 8.22, 1.4 Hz),
7.75–7.87 (m, 2H), 7.91 (d, 1H, J = 1.32 Hz), 11.68 (bs, 1H, NH),
12.87 (bs, 1H, NH); 13C NMR δ ppm; 14.65, 108.18, 109.32, 111.95,
112.68, 118.26, 118.78, 119.21, 122.26, 123.61, 129.44, 130.51,
130.87, 131.04, 131.89, 132.56, 136.31, 139.65, 142.22, 149.84,
Yellow solid; Yield 93%, m.p. 208-209ꢀC; IR (KBR) ʋ (cm−1): 3218
(NH), 1634 (C=N), 1654 (CONH), 1H-NMR (DMSO-d6) δ ppm; 1.23 (d,
6H, 2xCH3), 2.91–2.95 (m, 1H, -CH), 5.71 (s, 2H, N-CH2-CO), 6.99 (d,
1H, J = 8.13 Hz), 7.13 (dd, 2H, J = 8.01, 1.4 Hz), 7.22–7.27 (m, 1H),
7.32–7.41 (m, 2H), 7.48–7.53 (m, 2H), 7.59 (d, 1H, J = 1.3 Hz),
7.70–7.74 (m, 2H), 11.84 (bs, 1H, NH), 12.78 (bs, 1H, NH); 13C NMR δ
ppm; 18.11, 41.56, 108.67, 109.13, 111.57, 112.00, 117.19, 118.78,
119.21, 122.12, 123.54, 129.97, 130.78, 131.09, 132.55, 136.43,
139.13, 142.02, 149.58, 151.29, 157.11, 158.18, 163.24; Anal calcd
for C26H22ClN5O2 (471.15); C, 66.17; H, 4.70; N, 14.84; Found C,
66.20; H, 4.73; N, 14.79.
150.03, 157.11, 160.06, 163.25; Anal calcd for
C24H18FN5O2
(427.14); C, 67.44; H, 4.24; N, 16.38; Found C, 67.46; H,
4.28; N, 16.31.
5.8
|
(E)-N0-(2-chlorobenzylidene)-
5.11
|
(Z)-N0-([1H-indol-3-yl]methylene)-
2-(2-(4-isopropylphenyl)-1H-benzo[d]imidazol-1-yl)
aceto hydrazide (5 h)
2-(2-[3-fluorophenyl]-1H-benzo[d]imidazol-1-yl)
acetohydrazide (5 k)
Light yellow solid; Yield 80%, m.p. 241-243ꢀC; IR (KBR) ʋ (cm−1):
3336 (NH), 1633 (C=N), 1661 (CONH), 1H-NMR (DMSO-d6) δ ppm;
1.21 (d, 6H, 2xCH3), 2.94–2.99 (m, 1H, -CH), 5.64 (s, 2H, N-CH2-CO),
7.38–7.44 (m, 4H), 7.50–7.56 (m, 3H), 7.70 (d, 1H, J = 8.1 Hz),
7.74–7.79 (m, 3H), 8.44 (s, 1H), 8.97 (s, 1H), 12.07 (s, 1H, NH); 13C
NMR δ ppm; 18.33, 41.08, 109.49, 111.13, 117.09, 119.12, 120.22,
121.18, 122.45, 123.65, 126.35, 127.51, 129.24, 131.78, 132.51,
133.09, 135.11, 138.62, 142.47, 149.63, 150.56, 162.13, 162.56,;
Anal calcd for C25H23ClN4O (430.16); C, 69.68; H, 5.38; N, 13.00;
Found C, 69.59; H, 5.41; N, 13.09.
White yellow solid; Yield 90%, m.p. 235-237ꢀC; IR (KBR) ʋ (cm−1):
3229 (NH), 1593 (C=N), 1685 (CONH), 1H-NMR (DMSO-d6) δ ppm;
5.79 (s, 2H, N-CH2-CO), 7.01–7.15 (m, 4H), 7.26–7.32 (m, 2H), 7.34
(s, 1H), 7.51–7.60 (m, 3H), 7.68 (dd, 1H, J = 8.22, 1.4 Hz), 7.71 (dd,
1H, J = 8.2, 1.45 Hz), 7.88 (d, 1H, J = 1.32 Hz), 8.70 (s, 1H, CH=N),
11.71 (bs, 1H, NH), 12.56 (bs, 1H, NH); 13C NMR δ ppm; 108.14,
109.45, 111.23, 112.65, 117.17, 118.90, 119.11, 122.32, 123.21,
129.18, 130.98, 131.34, 132.64, 132.87, 133.31, 136.98, 140.36,
142.41, 149.91, 150.20, 154.33, 157.61, 160.54, 163.88, 168.14;
Anal calcd for C24H18FN5O (411.15); C, 70.06; H, 4.41; N, 17.02;
Found C, 70.09; H, 4.44; N, 16.95.
5.9
|
(E)-N0-(3,4-dichlorobenzylidene)-
2-(2-(4-isopropylphenyl)-1H-benzo[d]imidazol-1-yl)
acetohydrazide (5i)
5.12
|
(E)-2-(2-[3-fluorophenyl]-1H-benzo[d]
imidazol-1-yl)-N0-([4-oxo-4H-chromen-3-yl]
methylene)acetohydrazide (5 L)
Off white solid; Yield 79%, m.p. 253-255ꢀC; IR (KBR) ʋ (cm−1): 3248
(NH), 1617 (C=N), 1685 (CONH), 1H-NMR (DMSO-d6) δ ppm; 1.22 (d,
6H, 2xCH3), 2.93–2.97 (m, 1H, -CH), 5.62 (s, 2H, N-CH2-CO),
7.01–7.14 (dd, 2H, J = 8.32, 1.21 Hz), 7.21–7.28 (m, 2H), 7.32 (dd,
1H, J = 8.1, 1.2 Hz), 7.52 (dd, 1H, J = 8.4, 1.3 Hz), 7.61 (d, 1H,
J = 8.1 Hz), 7.65 (d, 1H, J = 8.1 Hz), 7.71–7.80 (m, 3H), 8.65 (s, 1H,
CH=N), 12.23 (s, 1H, NH); 13C NMR δ ppm; 18.13, 41.23, 109.12,
111.45, 117.19, 119.19, 120.57, 121.87, 122.44, 123.88, 126.24,
127.48, 129.29, 131.66, 132.87, 133.01, 135.16, 138.22, 142.76,
White cream solid; Yield 80%, m.p. 274-275ꢀC; IR (KBR) ʋ (cm−1):
3289 (NH), 1608 (C=N), 1659 (CONH), 1H-NMR (DMSO-d6) δ ppm;
5.77 (s, 2H, N-CH2-CO), 7.25–7.32 (m, 3H), 7.51–7.60 (m, 4H), 7.68
(dd, 1H, J = 8.22, 1.4 Hz), 7.88 (d, 1H, J = 1.32 Hz), 8.01 (dd, 1H,
J = 8.7, 1.1 Hz), 8.10 (dd, 1H, J = 8.12, 1.2 Hz), 8.21 (m, 1H), 8.72 (s,
1H, CH=N), 8.93 (s, 1H, CH-O), 12.28 (bs, 1H, NH); 13C NMR δ ppm;
108.34, 109.31, 111.12, 112.45, 117.67, 118.88, 119.54, 122.89,
123.62, 129.45, 130.87, 131.87, 132.05, 132.88, 133.36, 136.56,
140.66, 142.69, 149.33, 150.66, 154.61, 157.62, 160.51, 163.96,
149.87, 150.43, 162.22, 164.66,; Anal calcd for
C25H23Cl2N4O

AHMAD ET AL.
9
168.24; Anal calcd for C25H17FN4O3 (440.13); C, 68.18; H, 3.89; N,
12.72; Found C, 68.21; H, 3.84; N, 12.70.
5.16
|
(E)-2-(2-(3-hydroxy-4-methoxyphenyl)-1H-
benzo[d]imidazol-1-yl)-N0-(5-nitro-2-oxoindolin-
3-ylidene)acetohydrazide (5p)
5.13
|
(E)-2-(2-[3-fluorophenyl]-1H-benzo[d]
Light brown solid; Yield 89%, m.p. 244-245ꢀC; IR (KBR) ʋ (cm−1):
3337 (NH), 1601 (C=N), 1658 (CONH), 1H-NMR (DMSO-d6) δ ppm;
3.42 (s, 3H, OCH3), 5.22 (bs, 1H, OH), 5.66 (s, 2H, N-CH2-CO),
6.91–6.92 (m, 1H), 7.06–7.07 (m, 1H), 7.27–7.37 (m, 2H), 7.49 (dd,
2H, J = 7.92, 7.68 Hz), 7.53–7.54 (m, 1H), 7.65 (t, 2H, J = 8.22 Hz),
7.72 (d, 1H, J = 7.26 Hz), 11.26 (bs, 1H, NH), 12.58 (bs, 1H, NH); 13C
NMR δ ppm; 44.33, 109.99, 111.11, 117.48, 119.37, 120.99, 121.38,
122.24, 122.95, 126.24, 127.06, 127.51, 129.20, 131.97, 132.50,
133.06, 135.62, 138.67, 142.46, 142.67, 150.94, 162.46, 162.80,
168.51; Anal calcd for C24H18N6O6 (486.13); C, 59.26; H, 3.73; N,
17.28; Found C, 59.31; H, 3.65; N, 17.41.
imidazol-1-yl)-N0-(3-methyl-4-oxonaphthalen-1[4H]-
ylidene)acetohydrazide (5 m)
Off white solid; Yield 89%, m.p. 289-291ꢀC; IR (KBR) ʋ (cm−1): 3316
(NH), 1633 (C=N), 1683 (CONH), 1H-NMR (DMSO-d6) δ ppm; 2.3 (s,
3H, CH3), 5.78 (s, 2H, N-CH2-CO), 6.81 (s, 1H, CH-C=N), 7.17–7.28
(m, 2H), 7.49 (dd, 1H, J = 8.26, 1.21 Hz), 7.61 (dd, 1H, J = 7.89,
1.32 Hz), 7.69–7.81 (m, 4H), 7.89–8.01 (m, 4H), 12.58 (bs, 1H, NH);
13C NMR δ ppm; 14.65, 108.56, 109.15, 111.34, 113.87, 117.76,
118.44, 119.65, 122.55, 125.78, 129.09, 130.22, 130.87, 131.16,
131.79, 132.98, 136.25, 140.22, 142.22, 144.36, 149.45, 150.67,
157.83, 160.88, 163.54, 168.32; Anal calcd for
C26H19FN4O2
(438.15); C, 71.22; H, 4.37; N, 12.78; Found C, 71.25; H,
4.39; N, 12.71.
6
|
Α-GLUCOSIDASE INHIBITION ASSAY
The enzyme assay was performed with slight modifications as men-
tioned earlier (Chapdelaine et al., 1978). The reaction mixture of
100 uL contained 50 mM phosphate buffer pH 6.8, 10 μl of 0.5 mM
test compound and 10 μl (0.0234 units, Sigma) of α-glucosidase (Cat
No. 5003-1KU Type I from yeast) prepared in same buffer. The con-
tents were mixed and incubated at 37ꢀC for 10 min. After given time,
absorbance was taken at 400 nm using Synergy HTX 96-well plate
reader (BioTek, USA). The reaction was started by the addition of
10 μl 0.5 mM p-nitrophenyl-α-D-glucopyranoside (Sigma) substrate
and incubation continued for further 30 minutes. After given time the
absorbance was measured. Both positive and negative controls were
included and assay was done in triplicate. The percent inhibition was
calculated by the help of following equation. The active compounds
were serially diluted and assayed against the enzyme. The data
obtained was used to calculate IC50 values by EZ-Fit Enzyme Kinetics
software from Perrella Scientific Inc. Amherst, USA. IC50 value is the
concentration at which the enzyme activity is inhibited by 50%.
5.14
|
(E)-2-(2-(3-fluorophenyl)-1H-benzo[d]
imidazol-1-yl)-N0-(1-[4-fluorophenyl]ethylidene)
acetohydrazide (5n)
Yellow solid; Yield 92%, m.p. 235-236ꢀC; IR (KBR) ʋ (cm−1): 3322
(NH), 1621 (C=N), 1681 (CONH), 1H-NMR (DMSO-d6) δ ppm; 2.36 (s,
3H, CH3), 5.77 (s, 2H, N-CH2-CO), 7.17–7.22 (m, 3H), 7.28–7.36 (m,
3H), 7.41 (ddd, 1H, J = 8.17, 1.25 Hz), 7.51–7.68 (m, 4H), 7.75 (dd,
1H, J = 8.24, 1.3 Hz), 12.65 (bs, 1H, NH); 13C NMR δ ppm; 14.65,
108.43, 109.65, 111.12, 112.14, 118.67, 118.34, 119.87, 122.45,
123.76, 129.22, 130.76, 131.56, 132.00, 136.22, 139.68, 142.14,
149.76, 157.04, 160.26, 163.88; Anal calcd for
C23H18F2N4O
(404.14); C, 68.31; H, 4.49; N, 13.85; Found C, 68.36; H,
4.56; N, 13.83.
(E)-N0-(5-fluoro-2-oxoindolin-3-ylidene)-
Inhibitionð%Þ = ðAbsControl – AbsTest=AbsControlÞ x100
5.15
|
2-(2-(3-hydroxy-4-methoxyphenyl)-1H-benzo[d]
imidazol-1-yl)acetohydrazide (5o)
Light orange solid; Yield 85%, m.p. 212-214ꢀC; IR (KBR) ʋ (cm−1):
3211 (NH), 1625 (C=N), 1677 (CONH), 1H-NMR (DMSO-d6) δ ppm;
3.49 (s, 3H, OCH3), 5.37 (bs, 1H, OH), 5.79 (s, 2H, N-CH2-CO), 6.78
(d, 1 H, J = 8.11, 1.6 Hz), 6.91–7.01 (m, 4H), 7.21–7.26 (m, 1H), 7.43
(d, 1H, J = 1.2 Hz), 7.26–7.38 (m, 2H), 7.72 (d, 1H, J = 7.26 Hz), 11.45
(bs, 1H, NH), 12.91 (bs, 1H, NH); 13C NMR δ ppm; 44.18, 109.45,
110.78, 117.25, 119.98, 120.55, 121.65, 122.36, 123.01, 126.17,
127.24, 127.52, 129.28, 131.17, 132.69, 133.22, 135.84, 138.24,
142.95, 142.31, 150.28, 162.17, 162.36, 168.55; Anal calcd for
7
|
MOLECULAR DOCKING
Since crystal structure of α-glucosidase is not available from the PDB,
its homology model was built (using oligo-1,6-glucosidase as a tem-
plate) and validated according to reported method (Chaudhry
et al., 2017). Briefly, a search on BLAST database revealed oligo-1,-
6-glucosidase (PDB ID: 3A4A) from Saccharomyces cerevisiae among
the top matched results and was therefore selected to be used as a
template. Oligo-1,6-glucosidase shares 72% identity and 85% similar-
ity with α-glucosidase sequence (Park et al., 2008). Sequence align-
ment was carried out using Needleman-Wunsch global alignment
C
24H18FN5O4 (459.13); C, 62.74; H, 3.95; N, 15.24; Found C,
62.78; H, 3.99; N, 15.21.

10
AHMAD ET AL.
crystallography. Acta Crystallographica. Section D, Biological Crystallog-
raphy, 66, 12–21.
Chohan, Z. H., Arif, M., Shafiq, Z., Yaqub, M., & Supuran, C. T. (2006). In
algorithm embedded in Chimera (Pettersen et al., 2004). Structure
was modeled using Modeler (Šali and Blundell, 1993). Ramachandran
plot was constructed using Molprobity (Chen et al., 2010). Before
docking studies, the structures of compounds were optimized using
semi-empirical PM3 method in HyperChem (Eddouks et al., 2017).
Molecular docking studies were carried out using BioSolveIT's LeadIT
software (Sher and Alyemeni, 2011). The docked conformations were
visualized in Discovery Studio Visualizer 4.0 (Abdel-Sattar
et al., 2009).
vitro antibacterial, antifungal
&
cytotoxic activity of some
isonicotinoylhydrazide Schiff's bases and their cobalt (II), copper (II),
nickel (II) and zinc (II) complexes. Journal of Enzyme Inhibition and
Medicinal Chemistry, 21, 95–103.
Cui, Z., Li, Y., Ling, Y., Huang, J., Cui, J., Wang, R., & Yang, X. (2010). New
class of potent antitumor acylhydrazone derivatives containing furan.
European Journal of Medicinal Chemistry, 45, 5576–5584.
da Silva, Y. K. C., Augusto, C. V., de Castro Barbosa, M. L., de Albuquerque
Melo, G. M., de Queiroz, A. C., Dias, T. d. L. M. F., Júnior, W. B.,
Barreiro, E. J., Lima, L. M., et al. (2010). Synthesis and pharmacological
evaluation of pyrazine N-acylhydrazone derivatives designed as novel
analgesic and anti-inflammatory drug candidates. Bioorganic & Medici-
nal Chemistry, 18, 5007–5015.
ACKNOWLEDGMENT
The authors would like to thank Bahauddin Zakariya University and
University of Nizwa for the generous support of this project. We
thank analytical and technical staff for assistance. The project was
supported by grant from The Oman Research Council (TRC) through
the funded projects BFP/RGP/HSS/18/018 and Higher Education
Commission of Pakistan through Project No. 6975/NRPU/R&D.
Dhainaut, A., Tizot, A., Raimbaud, E., Lockhart, B., Lestage, P.,
&
Goldstein, S. (2000). Synthesis, structure, and neuroprotective proper-
ties of novel imidazolyl nitrones. Journal of Medicinal Chemistry, 43,
2165–2175.
Dimmock, J. R., Vashishtha, S. C., & Stables, J. P. (2000). Anticonvul-
sant properties of various acetylhydrazones, oxamoylhydrazones
and semicarbazones derived from aromatic and unsaturated car-
bonyl compounds. European Journal of Medicinal Chemistry, 35,
241–248.
CONFLICT OF INTEREST
The authors declare that they have no conflict of interest.
Eddouks, M., Ajebli, M., & Hebi, M. (2017). Ethnopharmacological survey
of medicinal plants used in Daraa-Tafilalet region (province of
Errachidia), Morocco. Journal of Ethnopharmacology, 198, 516–530.
Ergenç, N., Günay, N. S., & Demirdamar, R. (1998). Synthesis and antide-
pressant evaluation of new 3-phenyl-5-sulfonamidoindole derivatives.
European Journal of Medicinal Chemistry, 33, 143–148.
DATA AVAILABILITY STATEMENT
No data available
ORCID
Fonseca, V. (2003). Clinical significance of targeting postprandial and
fasting hyperglycemia in managing type 2 diabetes mellitus. Current
Medical Research and Opinion, 19, 631–635.
Gaba, M., Singh, S., & Mohan, C. (2014). Benzimidazole: An emerging scaf-
fold for analgesic and anti-inflammatory agents. European Journal of
Medicinal Chemistry, 76, 494–505.
Ajmal Khan
https://orcid.org/0000-0001-7851-6080
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How to cite this article: Ahmad MU, Rafiq M, Zahra B, et al.
Synthesis of benzimidazole based hydrazones as non-sugar
based α-glucosidase inhibitors: Structure activity relation and
molecular docking. Drug Dev Res. 2021;1–11. https://doi.org/
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