Design, synthesis and biological evaluation of some 2-(6-nitrobenzo[d]thiazol-2-ylthio)-N-benzyl-N-(6-nitrobenzo[d]thiazol-2-yl)acetamide derivatives as selective DprE1 inhibitors

Article abstract of DOI:10.1080/00397911.2019.1639756

Tuberculosis (TB) is an infectious disease and caused by various strains of mycobacteria. In the present study, pharmacophore model was developed using single ligand by ligand-based drug discovery approach. The key features responsible for DprE1 inhibitory activity were taken into consideration for developing pharmacophore. After the virtual screening, top 1000 hits were further subjected to docking study using GLIDE module, Schr?dinger. Docking studies have shown promising interaction with amino residues with better glide score. Ligand-based drug design approach yielded a series of 15, 2-(6-nitrobenzo[d]thiazol-2-ylthio)-N-benzyl-N-(6-nitrobenzo[d]thiazol-2-yl)acetamide derivatives. All synthesized derivatives were characterized using NMR, mass, CHN analysis. The synthesized compounds were screened for In vitro antitubercular activity against Mycobacterium tuberculosis (H₃₇Rv). Four compounds, 5g (MIC-1.01 μM); 5i (MIC-0.91 μM); 5k (MIC-0.82 μM); and 5o (MIC-1.04 μM) has shown promising activity compared to MIC of standard isoniazid (INH) and DprE1 enzyme inhibition was compared to BTZ043. Two halogen-substituted compounds have exhibited drastic enzyme inhibition.

Full text of DOI:10.1080/00397911.2019.1639756

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: https://www.tandfonline.com/loi/lsyc20
Design, synthesis and biological evaluation
of some 2-(6-nitrobenzo[d]thiazol-2-ylthio)-N-
benzyl-N-(6-nitrobenzo[d]thiazol-2-yl)acetamide
derivatives as selective DprE1 inhibitors
Jineetkumar Gawad & Chandrakant Bonde
To cite this article: Jineetkumar Gawad & Chandrakant Bonde (2019): Design, synthesis
and biological evaluation of some 2-(6-nitrobenzo[d]thiazol-2-ylthio)-N-benzyl-N-(6-
nitrobenzo[d]thiazol-2-yl)acetamide derivatives as selective DprE1 inhibitors, Synthetic
Communications, DOI: 10.1080/00397911.2019.1639756
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https://doi.org/10.1080/00397911.2019.1639756
Design, synthesis and biological evaluation of some
2-(6-nitrobenzo[d]thiazol-2-ylthio)-N-benzyl-N-(6-
nitrobenzo[d]thiazol-2-yl)acetamide derivatives as selective
DprE1 inhibitors
Jineetkumar Gawad
and Chandrakant Bonde
Department of Pharmaceutical Chemistry, School of Pharmacy and Technology Management, SVKM’s
NMIMS, Dhule, India
ABSTRACT
ARTICLE HISTORY
Received 19 April 2019
Tuberculosis (TB) is an infectious disease and caused by various strains
of mycobacteria. In the present study, pharmacophore model was
developed using single ligand by ligand-based drug discovery
approach. The key features responsible for DprE1 inhibitory activity
were taken into consideration for developing pharmacophore. After
the virtual screening, top 1000 hits were further subjected to docking
KEYWORDS
Tuberculosis; benzothiazole;
DprE1 enzyme;
aryl aldehydes
€
study using GLIDE module, Schrodinger. Docking studies have shown
promising interaction with amino residues with better glide score.
Ligand-based drug design approach yielded a series of 15, 2-(6-nitro-
benzo[d]thiazol-2-ylthio)-N-benzyl-N-(6-nitrobenzo[d]thiazol-2-yl)ace-
tamide derivatives. All synthesized derivatives were characterized
using NMR, mass, CHN analysis. The synthesized compounds were
screened for In vitro antitubercular activity against Mycobacterium
tuberculosis (H37Rv). Four compounds, 5g (MIC-1.01 lM); 5i (MIC-
0.91 lM); 5k (MIC-0.82 lM); and 5o (MIC-1.04 lM) has shown promis-
ing activity compared to MIC of standard isoniazid (INH) and DprE1
enzyme inhibition was compared to BTZ043. Two halogen-substituted
compounds have exhibited drastic enzyme inhibition.
GRAPHICAL ABSTRACT
DprE1-Ligand Complex
R2
R1
N
S
N
O
NO2
S
N
O2
N
S
Newly Synthesized Compounds
O
HO
O
O
O
O-
HO
DprE1
O
O
O-
H
P
H
P
OR
OR
HO
O
HO
OH
FAD
FADH2
DPX
DPR
CONTACT Jineetkumar Gawad
jineetkumar.gawad@nmims.edu
Department of Pharmaceutical Chemistry, School
of Pharmacy and Technology Management, SVKM’s NMIMS, Shirpur Campus, Dhule 425 405, India.
Supplemental data for this article can be accessed on the publisher’s website
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/lsyc.
ß 2019 Taylor & Francis Group, LLC

2
J. GAWAD AND C. BONDE
Introduction
Tuberculosis (TB) is an infectious airborne disease, mostly affecting young adults in
their productive years. It is a serious concern to mankind claiming nearly 2 million lives
and causing 9.8 million new infections each year. In the last few decades, there is a sub-
stantial increase in the incidences of tuberculosis due to the development of resistant
Mycobacterium tuberculosis.[1] According to the recent World Health Organization
(WHO) report, TB infection is one of the leading cause of death worldwide. Treatment
of TB has been always depending on the drugs used for a long time, such as isoniazid,
rifampicin, ethambutol, and pyrazinamide etc. While the multidrug resistant (MDR)
and extensively drug resistant (XDR) tuberculosis have proven these drugs to be less
effective and nowadays ineffective.[2,3] Increase in drug-resistant strains of M. tubercu-
losis strictly needs the designing of novel antitubercular molecules to serve the society
in a better way. TB is also a reason for decreasing the life expectancy and standards of
health not only in developing countries but also in developed as well.[4,5]
Unfortunately, no new and effective anti-TB drugs have been developed in the past
couple of decades. The research on drugs against drug-resistant strains of M. tubercu-
losis remains a significant challenge. Research groups have to find new targets with
attractive and promising microbiological properties for tackling tuberculosis with target-
based drug discovery. Among the explored targets, decaprenyl-phosphoryl-b-D-ribose-
2-epimerase (DprE1), which is the key enzyme involved in the arabinogalactan biosyn-
thesis of Mycobacterium cell wall, DprE1 is essential for the survival of M. tuberculosis.
The enzyme is crucial and conservative for mycobacterial cell wall biosynthesis.[6–8]
DprE1 catalyzes the FAD-dependent oxidation of decaprenylphosphoryl-b-D-ribose
(DPR) to decaprenyl-phosphoryl-20-keto-D-erythro-pentofuranose (DPX). DPX is then
reduced by decaprenyl-phospho-20-keto- D- arabinose reductase (DprE2) to generate
DPA, which is the indispensable component of Mycobacterium cell wall. Since there is
no alternative way to synthesize DPX, DprE1 becomes a druggable target. Targeting
DprE1 with small-molecule inhibitors has emerged as a promising strategy for anti-TB
therapy. For the past few years, DprE1 inhibitors, like BTZs and TCA1, were found to
cause Mycobacterium death by covalently or non-covalently binding to the enzyme
DprE1.[9,10] Benzothiazole derivatives are used as a component like local anesthetics,
hypoglycemic agents, carbonic anhydrase inhibitors, enzyme inhibitors, antimicrobial
agents, anticancers, antitubercular agents, central dopaminergic agents.[11–22] Previously,
several successful attempts were made to construct benzothiazole[23–26] and benzothia-
zole containing compounds for therapeutic purpose. Here, we have made a successful
attempt to design and synthesize some new benzothiazole substituted compounds as
antitubercular agents with specific DprE1 inhibitory activity which will cause the death
of M. tuberculosis.
Results and discussion
Pharmacophore modeling, virtual screening and docking studies
Pharmacophore model was generated with single ligand by using Develop common
pharmacophore hypothesis of maestro. Single ligand was used to develop

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Figure 1. Selected Pharmacophore hypotheses (a) and overlapping of four compounds (b).
Table 1. Data of the in vitro studies for MIC for M. tuberculosis (H37Rv),
IC50 for DprE1 inhibition study.
IC50
Antitubercular activity MIC
(mM)
Compound ID
Glide Score
(lM) on H37RV
DprE1
ꢁ
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
5m
5n
5o
ꢀ6.342
ꢀ6.229
ꢀ6.969
ꢀ5.969
ꢀ6.937
ꢀ6.166
ꢀ7.708
ꢀ6.545
ꢀ8.348
ꢀ6.599
ꢀ7.641
ꢀ5.522
ꢀ6.854
ꢀ6.234
ꢀ7.211
–
2.41
3.74
3.23
2.48
2.81
2.10
1.01
2.06
0.91
3.35
0.82
2.79
3.04
2.16
1.04
0.31
–
NT
NT
NT
NT
NT
NT
14.1 1.7
NT
12.7 0.9
NT
14.8 2.4
NT
NT
NT
11.2 1.5
–
0.084
–
Isoniazid (INH)
BTZ-043
Co-crystal Ligand
–
ꢀ5.725
–
NT: not tested.
pharmacophore. The features necessary to exhibit DprE1 inhibitory activity were con-
sidered. The developed model (Fig. 1) was subjected to virtual screening. Model was
€
screened for a database of compounds provided by Schrodinger, USA, comprising of
around 8,20,000 compounds. After screening, top 1000 hits were subjected to molecular
docking studies. The molecular docking study was carried out to discover the flexible
binging modes for ligands with an enzyme (DprE1). The docking simulations were run
€
by the Glide docking tool of Maestro molecular modeling interphase (Schrodinger,
USA). All the docking parameters were kept as default. OPLS2005 force field was
applied. The receptor employed here was specifically DprE1 (PDB code: 4KW5)
obtained from RCSB Protein Data Bank (RCSB-PDB). The initial crystal structure con-
sisted of the bound ligands (glycerol moieties), it was removed and the missing loops
were added. The docking scores of all the compounds were presented in (Table 1). The

4
J. GAWAD AND C. BONDE
Figure 2. Binding modes of compounds 5c, 5g, 5i, and 5o with DprE1 target cavity, which represents
hydrogen bonds, hydrophobic interactions and pi-pi interactions.

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5
Figure 2. Continued.
Figure 3. Binding modes of co-crystal ligand (PDB ID-4KW5).
interacting amino acid residues were identified as Lys418, Trp230, Asp389, Phe313,
Asn385, etc. The results were promising and interesting compared to previously
reported findings. Among all compounds, here we have discussed four compounds with
maximum docking score as well as antitubercular activity (Fig. 2) along with 2 D and
3 D docking poses of co-crystallised ligand (Fig. 3). In compound 5g, Lys418 has shown
H-bond with one nitrogen of benzothiazole ring and pi-pi stacking with substituted
benzothiazole. In compound 5i, Trp230 has shown overlapping pi-pi stacking with sub-
stituted chlorobenzyl and oxygen of nitro of benzothiazole has formed H-bond with
Asn385. Meanwhile, compound 5k, emphasized that substituted benzothiazole has

6
J. GAWAD AND C. BONDE
F
O
S
F
O
F
F
F
N
N
N
F
OH
H
N
N
N
H
N+
N
HN
OH
O
O-
Cl
O
F
O
F
HO
OH
OH
N
N
F
OH
O
HO
NH
F
N
N
H
NH
N
N
S
S
HO NH
O
O
O
N
S
O
O
O
N
N
O
O
HN
O
O
S
HN
N
S
N
H
S
N
O
O
HN
O
O
N
S
Figure 4. Representative compounds from top 1000 hits after virtual screening.
exhibited fantastic interactions, the nitrogen of nitro has formed H-bond withTrp16,
Lys418 has shown dual interaction, it has formed H-bond with the oxygen of amide
and has formed a salt bridge with substituted benzothiazole ring. Gly117 has formed H-
bond with the nitrogen of benzothiazole. Lastly, in compound 5o, Lys418 has shown pi-
pi stacking with benzothiazole ring and Gly117 has formed H-bond with the nitrogen
of benzothiazole ring. Interactions produced by these molecules are quite similar to the
lead molecule TCA1, this directs that substitution with benzothiazole nucleus may con-
tribute towards the DprE1 selectivity leading to the development of the target-specific
lead molecules for this series forming potent antitubercular agents. After the virtual
screening, from top 1000 hits, some of the representative compounds were presented in
Figure 4. Among these structures, different structural building blocks were present but
benzothiazole was present in more number of structures. Also, by considering the litera-
ture and the importance of benzothiazole nucleus for therapeutic applications, we
decided to synthesize its substituted derivatives.
Chemistry
Target molecules (5a–o) were synthesized in five steps as shown in Scheme 1. Initially,
6-nitrobenzo[d]thiazol-2-amine (1)[27] was synthesized by stirring 4-nitroaniline, potas-
sium thiocynate and dropwise added bromine using acetic acid as diluent. N-benzyli-
dene-6-nitrobenzo[d]thiazol-2-amine (2) was synthesized via condensation of
appropriate aryl benzaldehyde and 6-nitrobenzo[d]thiazol-2-amine in ethanol with a
catalytic amount of glacial acetic acid. Compound (2) in methanol was reduced to N-

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R1
R2
EtOH/CH3COOH
Reflux, 2h
KSCN
NO2
S
N
R1
CHO
NO2
NH2
NH2
N
S
Br2 in CH3COOH
R2
Ar-CHO
N
NO2
4-nitroaniline
2
6-nitrobenzo[d]thiazol-2-amine
1
MeOH
NaBH4
Stirr, 1h
R1
R2
NO2
S
N
NH
ClCH2COCl
R1
TEA/ THF
Stirr, 1h
N
S
S
R2
3
N
Cl
SH
N
O2N
O
4
K2CO3
Reflux, 12 h
Acetone
R2
R1
N
N
S
NO2
S
O2N
O
S
N
5a-o
Scheme 1. Synthesis of 2-(6-nitrobenzo[d]thiazol-2-ylthio)-N-benzyl-N-(6-nitrobenzo[d]thiazol-2-yl)ace-
tamide derivatives.
benzyl-6-nitrobenzo[d]thiazol-2-amine (3) by using NaBH4. In the third step, N-benzyl-
2-chloro-N-(6-nitrobenzo[d]thiazol-2-yl)acetamide (4) was synthesized by acetylation of
the compounds (3) in tetrahydrofuran (THF) with chloroacetyl chloride. Finally, bimol-
ecular nucleophilic substitution (SN2) reaction between appropriate benzo[d]thiazole-2-
thiol and the compound (4) in the presence of potassium carbonate dissolved in acetone
has given the desired compound (5). Substitution with different aryl aldehydes has pro-
duced 15 new 2-(6-nitrobenzo[d]thiazol-2-ylthio)-N-benzyl-N-(6-nitrobenzo[d]thiazol-2-
yl)acetamide derivatives (5a–o).
The IR spectrum showed absorption bands at 1550–1500 cmꢀ1 (N–O str) confirms
the presence of nitro group, 1690 cmꢀ1 (C¼O str) confirms the amide, bands in the
range 2000–1650 cmꢀ1 indicates the presence of aromatic rings, 1440–1000 cmꢀ1 illus-
trates fluoro (C–F) substitution and 690–515 cmꢀ1 confirms the presence of bromo
1
compound. H NMR study displays the protons between d 7.1 and 8.8 belongs to the
aromatic ring of substituted benzothiazole. The 13C NMR studies indicate the aromatic
carbons. The compounds were also confirmed by mass and CHN analysis.
Biological evaluation
Mycobacterium tuberculosis H37Rv (ATCC 27294) to determine MIC of test compounds
with Isoniazid as a standard reference. After the incubation period of culture in the pres-
ence or absence of test compounds, the viability of bacteria was determined by observing
the color change from blue to pink of Resazurin mixture which acts as an indicator of
the inhibitory activity and potency. It was found that compounds 5g, 5i, 5k, and 5o
exhibited MIC between 0.82 and 1.04mM which is found to be a bit closer to the stand-
ard reference isoniazid with MIC of 0.31mM. The compounds with good MIC were found

8
J. GAWAD AND C. BONDE
to be substituted with halogens like chlorine and bromine which are good dual-acting
substitutions causing an electron withdrawing nature on the ring nucleus.
DprE1 activity and inhibition studies
This enzymatic assay was carried out on the selected compounds which have shown
good MIC in the cell cultures.[28–30] The UV-spectrophotometric method for 2,6
dichlorophenolindophenol (DCPIP) and DprE1 activity assay was carried out on the b-
D-ribofuranose (FPR) substrate as described earlier by Liav A. et al. the mixture was
incubated for 7 min at different concentrations of test compounds 5g, 5i, 5k, and 5o.
The inhibition concentration and enzyme activity in the absence of inhibitor were deter-
mined and reported in Table 1. Compounds 5g and 5i exhibited IC50 of 14.1 1.7 mM
and 12.7 0.9 mM, respectively, whereas 5k and 5o had IC50 of 14.8 2.4 and 11.2 1.5
respectively.
Conclusion
In this paper, we have reported a series of 2-(6-nitrobenzo[d]thiazol-2-ylthio)-N-benzyl-
N-(6-nitrobenzo[d]thiazol-2-yl)acetamide derivatives (5a–o). Newly synthesized com-
pounds were analyzed for their in vitro antitubercular activity on the strain H37RV of
M. tuberculosis. Among those compounds, four has shown comparatively impressive
activity. The active compounds, 5g, 5i, 5k, and 5o have shown good potency towards
M. tuberculosis strain. Pharmacophore model was generated using single ligand, after
the virtual screening, molecular docking studies were also carried out using the reported
crystal structure of DprE1, we studied flexible binding modes for the synthesized com-
pounds in comparison with the co-crystal reference molecule TCA1. Interestingly, four
compounds (5g, 5i, 5k, and 5o) have shown better glide score and antitubercular activ-
ity. Knowledge from the molecular docking studies emphasizes that further modifica-
tions are also possible in the series of molecules to develop better compounds for
potential DprE1 inhibitory activity. These most active four compounds were analyzed
for DprE1 enzyme specific studies. Interestingly, two compounds, i.e. 5i and 5o have
shown DprE1 inhibition. Previously, it was reported that nitro group is essential for
DprE1 inhibitory activity, as it gets reduced and forms adduct with Cys387 to exhibit
activity. Currently, presented molecular docking findings strikes on interactions of syn-
thesized chemical structures with various amino acid residues but does not showed any
interaction with Cys387 residue but has come up with promising glide score. By modi-
fying aliphatic and aromatic carbon centers, more potent DprE1 inhibitors can be
designed in the future.
Experimental
Materials and methods
Protein structure was downloaded from RCSB protein data bank along with co-crystal-
lized ligand present in it. Protein was prepared by using the protein preparation wizard
and ligands were prepared by using Ligprep tool (Maestro 11.8.012).[31]

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Pharmacophore hypothesis virtual screening and molecular docking studies
The crystal structure of M. tuberculosis decaprenyl-phosphoryl-ribose 20-epimerase
(DprE1) complexed with co-crystallized ligand (PDB ID: 4KW5) was downloaded from
PDB data bank. Key features responsible for DprE1 enzyme inhibition were manually
identified and considered during selection of pharmacophore features. Pharmacophore
model was generated using PHASE module of Schrodinger. All calculations were per-
€
formed on a commercially available Maestro, Schrodinger, USA. Developed pharmaco-
phore hypothesis was screened for a library of around 8.2 lakhs of compounds. All the
parameters were kept as default. Molecular docking studies were performed by using
Glide module of Maestro 11.8.012. Docking of the top 1000 hits from virtual screening
was carried out on Glide docking module of Maestro 11.8.012 as per the Glide protocol
€
of Schrodinger. All the default parameters were used. For ligand preparation, the pH
was 7.0 2.0, force field OPLS2005 was applied and ionization was done using Epik.
For protein preparation, the pH was 7.0 2.0, force field was OPLS2005, ionization was
done using Epik and the water molecules within 3 Å were kept and rest were deleted.
General procedure for synthesis of 6-nitrobenzo[d]thiazol-2-amine (1)
A mixture of 4-nitroaniline (30 mmol) and potassium thiocyanate (30 mmol) was taken
in three-neck flask, bromine in acetic acid (2.6 mL of bromine in 12.5 mL of acetic acid)
was added dropwise using dropping funnel for initial 1 h. The reaction mixture was
continuously stirred for 6–7 h. After completion, the reaction mixture was filtered.
Filtrate was placed in ice-cold water and neutralized with ammonia solution. The pre-
cipitate was filtered, recrystallized with ethanol.[32]
Synthesis of substituted N-benzylidene-6-nitrobenzo[d]thiazol-2-amine (2)
Different substituted aromatic benzaldehydes (20 mmol), 6-nitrobenzo[d]thiazol-2-amine
(20 mmol) and glacial acetic acid (0.5 mL) in catalytic amount were refluxed in ethanol
(50 ml) for 2 h. After completion of the reaction, the mixture was cooled, precipitated
product was filtered, and recrystallized from ethanol.[33–35]
Synthesis of N-benzyl-6-nitrobenzo[d]thiazol-2-amine (3)
The compound 2 (10 mmol) was dissolved in methanol (50 ml). The reduction was car-
ried out by using sodium borohydride which was divided into four portions (4 ꢂ 0.15 g)
and added to the methanolic solution after intervals of every 15 min. After addition of
the last portion, reaction mixture was allowed to stir for 1 h at room temperature. The
excess of solvent was evaporated under reduced pressure, crude product was washed
with ether, dried, and recrystallized from ethanol.[36–38]
Synthesis of N-benzyl-2-chloro-N-(6-nitrobenzo[d]thiazol-2-yl)acetamide (4)
The compound 3 (2 mmol) was dissolved in tetrahydrofuran (25 ml) and further trie-
thylamine (1.5 ml) was added. The mixture was cooled in an ice bath and chloroacetyl

10
J. GAWAD AND C. BONDE
Table 2. Synthesis of compounds from 5a–o.
Compound ID
R1
R2
5a
5b
5c
5d
5e
5f
5g
5h
5i
–CH3
–OCH3
–F
–SCH3
–OCH3
–H
–H
–OH
–Cl
–CH3
OCH3
–H
–H
–H
–OH
–OCH3
–OCH3
–H
5j
5k
5l
–H
–H
–COCH3
–NO2
–H
–H
5m
5n
5o
–F
–NH2
–H
–F
–H
–Br
chloride (0.5 ml) was added dropwise with stirring. After the addition of chloroacetyl
chloride, the reaction mixture was stirred for additional 1 h at room temperature. The
solvent was evaporated, product was washed with water, ether then dried and recrystal-
lized from ethanol.[39,40]
Synthesis of 2-(6-nitrobenzo[d]thiazol-2-ylthio)-N-benzyl-N-(6-nitrobenzo[d]thiazol-
2-yl)acetamide (5)
The compound 4 (2 mmol), benzo[d]thiazole-2-thiol (mercaptobenzothiazole) and potas-
sium carbonate (eq.) in acetone (20 ml) was refluxed for 12 h. After TLC screening, the
solvent was evaporated under reduced pressure. The product 5 was washed with water,
dried, and recrystallized from ethanol. Various aryl aldehydes yieꢀld1ed different deriva-
tives (Table 2).[41] Yield: 41%. M.P. 172 C–174 ꢃC. IR v ¼ 1520 cm (N–O), 1660 cmꢀ1
1
(C¼O), 1690, 1720, 1750 cmꢀ1 (aromatic rings), 1420 cmꢀ1 (C–H). H NMR: (600 MHz,
DMSO) d ¼ 2.22 (3H, s), 2.24 (3H, s), 4.24 (2H, s), 5.14 (2H, s), 7.16 (1H, dd, J ¼ 8.2,
2.5 Hz), 7.15 (1H, dd, J ¼ 8.2, 2.0 Hz), 7.21 (1H, dd, J ¼ 2.0, 1.5 Hz), 7.98 (1H, dd,
J ¼ 9.8, 1.3 Hz), 8.12 (1H, dd, J ¼ 10.7, 2.5 Hz), 8.32–8.38 (2 H, m), 8.64–8.72 (1H, m).
13C NMR (100 MHz, DMSO) d (ppm) 19.4, 32.1, 51.7, 117.9, 121.9, 127.6, 133.9, 138.3,
142.3, 150.8, 164.9, 165.6. MS m/z: found for C25H19N5O5S3 found 565.9 (M–H)ꢀ:
564.05. Anal Found: C, 53.08; H, 3.39; N, 12.38, calcd: C, 53.10; H, 3.41; N, 12.40.
1
Full experimental detail, H and 13C NMR spectra, biological testing. This material
can be found via the “Supplementary Content” section of this articles webpage.
Acknowledgements
Authors are thankful to Dr. Rupesh Chikhale, University of Manchester, United Kingdom for
helping in DprE1 enzymatic assays.
ORCID
Jineetkumar Gawad
http://orcid.org/0000-0001-7196-2125

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