Synthesis and antitubercular activity of new 1,3,4-oxadiazoles bearing pyridyl and thiazolyl scaffolds

Article abstract of DOI:10.1016/j.bmcl.2016.05.093

In search of more potent and safe new antitubercular agents, here new 2-pyridinyl substituted thiazolyl-5-aryl-1,3,4-oxadiazoles (6a–o), have been designed and synthesized using thionicotinamide as a starting, following novel multistep synthetic route. An intermediate, pyridinyl substituted thiazolyl acid hydrazide (4) when condensed with benzoic acids/nicotinic acids (5a–o) in the presence of silica supported POCl₃yielded better to excellent yields of the title compounds. All the synthesized compounds (6a–o) and intermediate acid hydrazide (4) have been screened for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Ra (MTB) and Mycobacterium bovis BCG. Amongst them, 6f, 6j, 6l and 6o have revealed promising activity against M. bovis BCG at concentrations less than 3?μg/mL. These compounds have shown low cytotoxicity (CC₅₀: >100?μg/mL) towards four human cancer cell lines. Molecular docking study has also been performed against mycobacterial enoyl reductase (InhA) enzyme to gain an insight into the binding modes of these molecules and recorded good binding affinity. The ADME properties the title products have also been analyzed.

Full text of DOI:10.1016/j.bmcl.2016.05.093

Accepted Manuscript
Synthesis and Antitubercular Activity of New 1,3,4-Oxadiazoles Bearing Pyr-
idyl and Thiazolyl Scaffolds
Sambhaji T. Dhumal, Amarsinh R. Deshmukh, Manisha R. Bhosle, Vijay M.
Khedkar, Laxman U. Nawale, Dhiman Sarkar, Ramrao A. Mane
PII:
S0960-894X(16)30603-5
DOI:
http://dx.doi.org/10.1016/j.bmcl.2016.05.093
BMCL 23952
Reference:
To appear in:
Bioorganic & Medicinal Chemistry Letters
Received Date:
Revised Date:
Accepted Date:
31 March 2016
28 May 2016
31 May 2016
Please cite this article as: Dhumal, S.T., Deshmukh, A.R., Bhosle, M.R., Khedkar, V.M., Nawale, L.U., Sarkar, D.,
Mane, R.A., Synthesis and Antitubercular Activity of New 1,3,4-Oxadiazoles Bearing Pyridyl and Thiazolyl
Scaffolds, Bioorganic & Medicinal Chemistry Letters (2016), doi: http://dx.doi.org/10.1016/j.bmcl.2016.05.093
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Synthesis and Antitubercular Activity of New 1,3,4-Oxadiazoles Bearing
Pyridyl and Thiazolyl Scaffolds
a
a
a
b
Sambhaji T. Dhumal , Amarsinh R. Deshmukh , Manisha R. Bhosle , Vijay M. Khedkar ,
b
b
a*
Laxman U. Nawale , Dhiman Sarkar , Ramrao A. Mane
a
Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad,
4
31004, India.
b
Combi Chem-Bio Resource Centre, CSIR-National Chemical Laboratory, Pune, 411008,
India.
Corresponding Author: Email address- manera2011@gmail.com (R. A. Mane)
*
Abstract
In search of more potent and safe new antitubercular agents, here new 2-pyridinyl
substituted thiazolyl-5-aryl-1,3,4-oxadiazoles (6a-o), have been designed and synthesized
using thionicotinamide as a starting, following novel multistep synthetic route. An
intermediate, pyridinyl substituted thiazolyl acid hydrazide (4) when condensed with benzoic
acids/nicotinic acids (5a-o) in the presence of silica supported POCl yeilded better to
3
excellent yields of the title compounds. All the synthesized compounds (6a-o) and
intermediate acid hydrazide (4) have been screened for their invitro antitubercular activity
against Mycobacterium tuberculosis H37Ra (MTB) and Mycobacterium bovis BCG.
Amongst them, 6f, 6j, 6l and 6o have revealed promising activity against M. bovis BCG at
concentrations less than 3 µg/mL. These compounds have shown low cytotoxicity (CC50
:
>100 μg/mL) towards four human cancer cell lines. Molecular docking study has also been
performed against mycobacterial enoyl reductase (InhA) enzyme to gain an insight into the
binding modes of these molecules and recorded good binding affinity. The ADME properties
the title products have also been analysed.
Keywords: 1,3,4-Oxadiazole, Pyridine, Thiazole, Antitubercular activity, Molecular
Docking, Cytotoxicity.

Tuberculosis has become a serious global health problem as it is second leading cause
1
of death amongst infectious diseases. Though first line and second line multicomponent
2
pattern of treatments for tuberculosis are practiced but now they are facing serious threats.
The patterns need longer duration for treatment and therefore the pathogenic strains
3
responsible for tuberculosis are found to be acquiring resistance to the drugs and new forms
of tuberculosis like multidrug resistant tuberculosis (MDR TB) and extensively drug resistant
4
tuberculosis (XDR TB) are found to be emerging as new challenge for medicinal chemists.
Nowadays population of patients having HIV and TB as coinfections is increasing. To
address the above threats now more attention is found to be paid on the search of appropriate
5
drugs for treating both the diseases simultaneously and efficiently. Therefore chemists are
paying their more focus on creation of library of new analogues of existing drugs or new
chemical entities with hope to obtain the agents with potential antitubercular activity with
6
reduced toxicity and treatment duration.
Recently, in search of the newer effective antitubercular agents, various new sulphur,
nitrogen, and oxygen containing heterocyclic scaffolds like thiazole, pyridine, 1,3,4-
7
oxadiazole, oxazoline and imidazole have been synthesized and evaluated. The potential of
8
the pyridine derivatives has been well explored and are found to display antitubercular, anti-
9
10
11
inflammatory, insecticidal,
derivatives, reported by Rawat et al. have shown considerable antitubercular activity.
Thiazoles are well established as building blocks for generating leads and have displayed
and anticancer,
activities. Novel isoniazid-amidoether
1
2
1
3
broad spectrum of therapeutic activities. Thiazole is seen as a key scaffold in various
1
4
15
clinical agents. There is a brief review on thiazoles possessing antitubercular activity. New
bisthiazoles have also been recently reported and found to exhibit noteworthy antitubercular
1
6
and antimicrobial activities. Balkan and co-workers have synthesized some amino thiazoles
1
7
and thiazolylhydrazones and reported their antitubercular activity.
Azole class of compounds are gaining importance because of their key property
liphophilicity that influence the ability of the drug to reach the target by transmembrane
1
8
diffusion. 1,3,4-Oxadiazoles have exhibited wide range of biological activities such as-
1
9
20
21
22
23
antibacterial, antitubercular, antitumor, antifungal, anti-inflammatory. Oxadiazole
derivatives have also shown wide spectrum of antimicrobial activities and are key component
2
4
25
of antibiotic furamizole and antiretroviral raltegravil. 1,3,4-oxadiazole scaffold is found to
work as bioisosteres of amides and esters which helps substantially to enhance therapeutic
26
activities by participating in hydrogen bonding interactions with respective receptors.
Literature reveals that there is a scanty information on the molecules having scaffolds like
thiazole, 1,3,4-oxadiazole and pyridine in one molecular framework.

2
7
28
29
1
,3,4-Oxadiazoles clubbed separately with thiazoles,
pyridines,
quinolines, and pyrrols have shown enhanced invivo and invitro antimycobacterial activity
figure 1). Literature reveals that 1,3,4-oxadiazoles clubbed with thiazole having pyridyl
moiety are not reported.
Considering the urgent need of preparing library of new antitubercular agents and
indoles,
3
0
31
(
highly impressed by the antimicrobial activities, displayed by coupled azoles especially 1,3,4-
oxadiazoles, here we thought worthwhile to design and synthesize new hybrid 1,3,4-
oxadiazoles with thiazolyl and pyridyl ring systems in a single molecular framework with
hope to obtain the new molecules with enhanced antimycobacterial activity.
M. bovis BCG is gaining importance as a M. tuberculosis surrogate for rapid and safer
3
2
screening. BCG is manipulated safely and its genome sequence is more than 99% identical
3
3
to the M. tuberculosis H37Rv. Therefore here we have reported a multistep synthesis of new
-pyridinylsubstituted thiazolyl-5-aryl-1,3,4-oxadiazoles (6a-o) and their antimycobacterial
2
evaluation against Mycobacterium tuberculosis H37RA (MTB) and Mycobacterium bovis
BCG. Molecular docking study and in silico ADME predictions have been carried of the
synthesized compounds and results are discussed.
Figure 1. Some of the active pyridine, thiazole and 1,3,4-oxadiazole based anti-TB
derivatives.
The title compounds, 2-pyridinyl substituted thiazolyl-5-aryl-1,3,4-oxadiazoles (6a-o)
have been synthesized by following multistep route, starting from nicotinamide (Scheme 1).
Thionicotinamide (2) was freshly prepared by digesting nicotinamide (1) and phosphorus
3
4
pentasulphide in pyridine.
Thionicotinamide was then condensed with 2-chloro-
ethylacetoacetate in refluxed ethanol and obtained 5-carboethoxy-4-methyl(nicotinyl-2-
yl)thiazole (3) by following Hantzsch Synthesis. A mixture of hydrazine hydrate and the

carboethoxythiazole (3) was dissolved in ethanol and the solution was refluxed for getting the
respective acid hydrazide (4). When cyclocondensation of the acid hydrazide (4) and benzoic
o
acids/nicotinic acids (5a-o) was carried in silica supported POCl
3
at 100 C gave the title
compounds, 2-pyridinylsubstituted thiazolyl-5-aryl/pyridinyl-1,3,4-oxadiazoles (6a-o) with
moderate to better yields. The physical data of oxadiazoles (6a-o) is incorporated in Table S1
(
Supporting information).
All the newly synthesized compounds have been characterized using their IR, H
1
1
3
NMR, C NMR and HRMS spectral data. The IR spectrum of compound (6a) indicates the
-1
formation of product as it shows a characteristic absorption peak at 1577 cm which
1
corresponds to the C=N of azole. The H NMR spectrum of compound (6a) displays peaks, a
singlet at  2.95 ppm, due to the CH
3
and multiplets in the region at  7.41 to 8.10 and 8.15 to
9
.22 ppm for five phenyl protons and four pyridyl protons respectively. The presence of three
1
3
characteristics carbon signals are observed at  17.61, 165.27 and 165.93 ppm in C NMR
spectrum of (6a) owing to the signals of carbons of CH and the two oxadiazol ring carbons
3
respectively, confirming the presence of a 1,3,4-oxadiazole ring in (6a). The HRMS spectrum
further strengthen the structure assigned to (6a) as 2-Pyridinylsubstituted thiazolyl-5-phenyl-
+
1
,3,4-oxadiazole as it displays [M+H] ion peak at m/z 321.0805 for the molecular formula
C
17
H
12
4
N OS. Experimental procedures and spectral details of 1,3,4-oxadiazoles (6a-o) and
intermediates are given in supporting information.
Scheme 1. 2-pyridinylsubstituted thiazolyl-5-aryl-1,3,4-oxadiazoles (6a-o)

In a standard primary screening, all the newly synthesized compounds (6a-o) were
tested for their invitro antitubercular activity against M. tuberculosis H37Ra (ATCC 25177)
and M. bovis BCG (ATCC 35743) at concentrations of 30, 10 and 3 µg/ml using an
established XTT Reduction Menadione assay (XRMA) and NR (Nitrate reductase) assay,
3
5, 36
respectively.
Compounds showing 90% inhibition of bacilli at or lower than 30 µg/ml
were selected for further dose response curve. Rifampicin, a clinical drug was used as internal
reference. The newly synthesized compounds (6a-o) displayed excellent selectivity towards
M. bovis BCG as compared to M. tuberculosis H37Ra. Experimental section of antitubercular
activity is in supporting information. The results of the screening are recorded in Table 1
which is expressed as mean ± SD based on three independent experiments.
Table 1
Antitubercular screening results of compounds (6a-o).
Code
Antitubercular activity against M.bovis BCG
Antitubercular activity against M.tuberculosis
H37Ra
Active Dormant
Active
IC50 (µg/ml)
Dormant
a
b
MIC
IC 50 (µg/ml) MIC (µg/ml)
IC50 (µg/ml)
MIC
(µg/ml)
>30
MIC
(µg/ml)
>30
IC50
(µg/ml)
>30
(
µg/ml)
6
6
a
b
>30
>30
24.49±0.84
24.67±0.17
>30
>30
94.86±0.26
42.24±0.25
>30
>30
56.29±0.44
27.96±0.26
>30
>30
>30
>30
>30
>30
>30
>30
>30
>30
>30
>30
>30
>30
>30
>30
40.37±0.4
40.01±1.8
>30
>30
>30
>30
>30
>30
>30
>30
>30
>30
>30
>30
>30
>30
>30
>30
>30
>30
>30
>30
>30
>30
>30
>30
>30
>30
>30
>30
>30
>30
6
c
>30
>30
>30
>30
>30
>30
>30
>30
>30
>30
>30
>30
>30
6
d
6
e
>30
>30
>30
>30
6
f
5.16±0.10
>30
2.62±0.25
>30
4.77±0.50
>30
1.47±0.06
>30
6
6
g
h
>30
>30
>30
>30
>30
>30
6
i
>30
>30
6
j
5.84±0.31
>30
2.69±0.85
14.23±
4.91±0.15
>30
1.44±0.02
15.2±0.55
1.8±0.1
5.26±0.51
24.92±1.81
3.55±0.13
6
k
6
l
2.65±0.70
11.29±0.27
>30
1.46±0.35
7.2±0.54
22.52±0.48
1.68±0.05
3.95±0.23
10.36±0.43
>30
6
m
6
6
n
o
2.56±0.22
5.89±0.06
RIF
0.08±0.014 0.003±0.00018 0.05±0.012 0.0027±0.0001 0.02±0.001 0.0017±0.00 0.03±0.007 0.0024±0.
01 00018
MIC indicated minimum inhibitory concentration.
2
4
a
b
IC50 indicates 50% inhibitory concentration.
After obtaining antitubercular screening, The 1,3,4-oxadiazoles (6a-o) have also been
evaluated for toxicity on four human tumor cell lines using 96-well microtitre plate and CC50
3
7-39
values were determined.
Four human tumor cell lines including acute monocytic
leukemia cell line (THP-1), pancreatic adenocarcinoma (PANC-1), cervix adenocarcinoma
4
0
(
HeLa) and colon adenocarcinoma (HCT 116) were obtained using MTT assay with

paclitaxel as a positive control. The results are recorded in Table 2. It has been noticed that
all the derivatives, (6a-o) do not exhibit strong cytotoxicity toward the cell lines.
The selectivity of the compounds (6a-o) towards human cell lines against BCG is
determined via their selectivity index (Table 2).The selectivity index reflects the quantity of
the compound that is active against BCG but is not toxic towards host cells. A higher
selectivity index indicates that the compound can be used as a therapeutic agent. It was found
that oxadiazoles, 6l and 6o are having a selectivity index of ≥10 at dormant and active stages
of BCG, indicating their potential as antitubercular agents, and thus they should be
investigated further.
Table 2
Cytotoxicity and selectivity index of compounds (6a-o).
Invitro cytotoxicity of compounds (6a-o) towards human cancer cell lines with SD (±) values
Compounds
Code
THP-1
(Leukemia)
HCT-116
(Colon)
PANC-1
(Pancreas)
HeLa
(Cervix)
Selectivity Index
(SI)
CC50
CC50
CC50
CC50
Against
Active
BCG
Against
Dormant
BCG
6
6
a
b
>100
>100
>100
>100
>100
>100
>100
>100
3
2
3
1
6
c
>100
>100
>100
>100
>100
>100
>100
>100
>100
>100
>100
>100
>100
>100
>100
>100
1.85±0.49
>100
>100
>100
>100
>100
>100
>100
>100
>100
>100
>100
>100
>100
>100
>100
>100
>100
>100
>100
>100
>100
>100
>100
>100
>100
>100
>100
>100
2
3
2
3
6
d
6
e
>100
3
3
6
f
>100
19
3
21
3
6
6
g
>100
h
>100
3
3
6
i
>100
3
3
6
j
>100
17
3
20
3
6
k
>100
6
l
>100
38
9
25
10
3
6
m
>100
6
n
o
>100
3
6
>100
39
1250
-
17
714
-
Rifampicin
Paclitaxel
>100
0.1374±0.014
0.1279±0.043 0.0048±0.0001
In an effort to rationalize the observed biological results and to gain an insight into
binding mode and the thermodynamic interactions that govern the binding of the most active
new 1,3,4-oxadiazole derivatives; 6f, 6j, 6l, and 6o with the target enzyme, mycobacterial
enoyl reductase (InhA) molecular docking study was performed. The docking studies were
performed with Glide (Grid-Based Ligand Docking with Energetics program incorporated in
4
1-44
Schrodinger molecular modeling package.
The X-ray crystal structures of mycobacterium

tuberculosis enoyl-ACP reductase complexed with its inhibitor (pdb code: 4TZK) was
retrieved from the RCSB protein data bank (http://www.rcsb.org/pdb) and used as the
primary model for the docking study. In the absence of experimental resources to perform the
enzymatic assays, molecular docking approach has proved to be very beneficial to identify
the targets for different ligands. The 1,3,4-oxadiazole derivatives have been reported to
inhibit mycobacterial enoyl reductase (InhA) which formed the basis for selection of this
4
5-47
enzyme as the potential target.
Enzymes that comprise the fatty acid synthetase (FAS)
complex responsible for fatty acid biosynthesis are considered ideal targets for antitubercular
drugs. The enoyl-ACP (CoA)reductase (FabI/ENR/InhA) is a key regulatory enzyme in the
mycobacterial type II fatty acid biosynthesis pathway. Inhibition of this enzyme has shown in
the fast-growing model organism Mycobacterium smegmatis to inhibit mycolic acid synthesis
4
8
and induce cell lysis. The theoretical predictions from the molecular docking study were
found to be in harmony with the experimental antitubercular activity. All the four derivatives
6
f, 6j, 6l, and 6o were successfully docked into the active site of mycobacterial enoyl
reductase (InhA) with varying degrees of affinity to the active site residues. A detailed per-
residue interaction analysis was carried out to understand the various thermodynamic
components involved in the binding of these molecules which could further provided a
meaningful insight into binding patterns observed within the enzyme cavity. The
experimental details of the molecular docking study are presented in supporting information.
The minimum energy docked pose (Figure 2) of the most active molecule 6l revealed
that the compound binds with a docking score of -8.92 and an overall binding energy of -
5
3.97 kcal/mol. The binding energy provides an idea about the energy required to cover the
entire protein by a ligand and its putative interactions at the active site of the enzyme. Lower
the value for binding energy, tighter is the binding with the target. Analysis of the binding
pose of 6l showed that it is stabilized within the active site of InhA through an extensive
network of favorable Vander Waals interactions with Ala191(-1.99 kcal/mol), Lys165(-1.75
kcal/mol), Met161(-1.39 kcal/mol), Asp148 (-1.89 kcal/mol), 147(-2.28 kcal/mol), Gly96(-
1
.36 kcal/mol), Ile95(-1.42 kcal/mol) and Ser94(-1.41 kcal/mol) through the pyridine ring;
Leu218(-1.76 kcal/mol), Ile215 (-3.19 kcal/mol), Ile202(-1.13 kcal/mol), Ala157 (-1.50
kcal/mol), Met155 (-1.53 kcal/mol) and Met103(-1.39 kcal/mol) residues through the ortho-
methoxy phenyl ring; Met199 (-4.14 kcal/mol) Pro193 (-2.59 kcal/mol), Tyr158(-6.63
kcal/mol) and Phe149 (-7.86 kcal/mol) through the 1,3,4-oxadiazole ring and with Ile194(-
1
.41 kcal/mol) and Gly192(-1.15 kcal/mol) residues through the thiazole ring. Furthermore
significant electrostatic interactions were observed with Val189 (-1.15 kcal/mol), Lys165(-
.70 kcal/mol), Asp148 (-4.13 kcal/mol), Ser123 (-1.53 kcal/mol), Ile95 (-1.90 kcal/mol)
4

His93 (-1.88 kcal/mol), Glu219 (-4.27 kcal/mol), Glu210 (-4.79 kcal/mol), Glu209 (-
.35kcal/mol), Arg195 (-1.92 kcal/mol), Phe149 (-1.88 kcal/mol), Tyr158 (-2.13 kcal/mol),
Met199 (-1.78 kcal/mol), Pro193 (-2.60 kcal/mol), Gly192 (-2.02 kcal/mol) and Pro156 (-
.90 kcal/mol) optimally stabilizing the molecule in the active site of InhA. Additionally
three significant pi-pi stacking interactions between the 1,3,4-oxadiazole ring and Phe149
1.02Å), Tyr158 (1.75Å) and Pro193 (1.95Å) residue were also observed. A very prominent
3
1
(
hydrogen bonding interaction was observed between the pyridine nitrogen and the Lys165
side chain (2.06Å) contributing further to the stability of the molecule within the active site.
Hydrogen bonding interaction anchors the ligand into the active site thereby determining the
orientation of the molecule in the 3D space and also facilitates the steric and electrostatic
interactions.
Figure 2. Binding mode of 6l into the active site of InhA predicted by molecular docking.
Figure 3. Binding mode of 6f into the active site of InhA predicted by molecular docking.
Figure 4. Binding mode of 6j into the active site of InhA predicted by molecular docking.

Figure 5. Binding mode of 6o into the active site of InhA predicted by molecular docking.
Docking of the compounds 6f, 6j and 6o also revealed the presence of a similar
binding mode as observed for 6l. The per residue ligand interaction energy distribution
showed that these compounds as well are anchored to the active site of InhA through a series
of favorable Vander Waals and electrostatic interactions along with few pi-pi stacking
interactions. The results of molecular docking study for all the four derivatives 6f, 6j, 6l, and
6
o are summarized in Table S2 (supporting information). These findings suggest that
systematic alterations around these leads through iterative synthesis and docking have the
potential to gradually identify a potent antitubercular candidate.
In silico ADME profile of newly synthesized 2-pyridinylsubstituted thiazolyl-5-aryl-
1
,3,4-oxadiazoles (6a-o) has been reported. The success of a drug is determined not only by
good efficacy but also by an acceptable ADME (absorption, distribution, metabolism and
excretion) profile. It is observed that all the synthesized compounds exhibited a good % ABS
ranging from 70.87 to 86.68 % in Table S3 (supporting information). The pharmacokinetic
data obtained for all the synthesized compounds (6a-o), was found to be within the range of
accepted values. Compounds 6a, 6b, 6c, 6d, 6e, 6f, 6h, 6i, 6j, 6k, 6l, 6m, 6n and 6o have not
violated Lipinski's rule of five. However, compound 6g violated Lipinski’s rule of five (milog
P ≤ 5). A molecule likely to be considered to develop an orally active drug candidate
provided it only violates one of the following four criteria’s: miLog P (octanol-water partition
coefficient) ≤5, molecular weight ≤500, number of hydrogen bond acceptors ≤10 and number
4
9
of hydrogen bond donors ≤5.
In conclusion, new 2-pyridinyl substituted thiazolyl-5-aryl-1,3,4-oxadiazoles (6a-o)
were synthesized and evaluated against M. tuberculosis and M.bovis BCG.. Among these
oxadiazoles, 6f, 6j, 6l, and 6o have displayed significant antitubercular activity against
Mycobacterium Bovis BCG. Out of these screened compounds, 6l and 6o are found to be very
good inhibitors to M.bovis BCG. These compounds, 6l and 6o have shown 2.65 µg/ml and
2
.56 µg/ml MIC against active stage of M.bovis BCG, respectively. All the newly synthesized

compounds were evaluated for their cytotoxic effect against four human cancer cell lines,
HeLa, THP-1, HCT 116, and PANC-1. Compounds 6l and 6o have displayed low
cytotoxicity (CC50: >100 μg/mL). Molecular docking study could reveal the binding
conformations of these compounds in the active site of potential target InhA and the
involvement of residues that could not be implicated from invitro enzyme-inhibitor study.
Furthermore it could provide a quantitative insight into various bonded and non-bonded
interactions which can be systematically alerted to arrive at potent candidates. So it can be
concluded from the above observations that the 1,3,4-oxadiazoles bearing pyridyl and
thiazolyl scaffolds offers an attractive lead series for the discovery of novel antitubercular
agents.
Acknowledgments
Authors are thankful to Professor D. B. Ingle for his invaluable discussions and guidance.
Authors acknowledge to CDRI, Lucknow for providing spectral facilities.Authors are also
grateful to National Chemical Laboratory (NCL), Pune for antitubercular evaluation and
Schrodinger Inc for providing the Demo license of Schrodinger Suite, and especially Craig
Coel for his valuable support. One of the authors STD is grateful to U.G.C., New Delhi, India
for financial assistance in the form of NET Senior Research Fellowship.
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Graphical abstract
Graphical Abstract
Synthesis and Antitubercular Activity of New 1,3,4-Oxadiazoles Bearing
Pyridyl and Thiazolyl Scaffolds
a
a
a
b
Sambhaji T. Dhumal , Amarsinh R. Deshmukh , Manisha R. Bhosle , Vijay M. Khedkar ,
b
b
a*
Laxman U. Nawale , Dhiman Sarkar , Ramrao A. Mane
a
Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad,
4
31004, India.
b
Combi Chem-Bio Resource Centre, CSIR-National Chemical Laboratory, Pune, 411008,
India.
Corresponding Author: Email address- manera2011@gmail.com (R. A. Mane)
*
Binding mode of the most active
compound (6l)
New 2-pyridinylsubstituted thiazolyl-5-aryl-1,3,4-oxadiazoles (6a-o) have been synthesized
via novel synthetic route. Among these compounds, 6f, 6j, 6l and 6o have revealed promising
activity against M. bovis BCG. The molecular docking and drug likeness on the basis of
ADME profile of the new entities have also been reported.