Novel pyrazole integrated 1,3,4-oxadiazoles: Synthesis, characterization and antimicrobial evaluation

Article abstract of DOI:10.1016/j.bmcl.2013.11.029

A novel series of 2-(5-methyl-1,3-diphenyl-1H-pyrazol-4-yl)-5-phenyl-1,3,4- oxadiazoles 7(a-m) were synthesized either by cyclization of N′-benzoyl-5-methyl-1,3-diphenyl-1H-pyrazole-4-carbohydrazide 4a using POCl₃ at 120 C or by oxidative cycli

Full text of DOI:10.1016/j.bmcl.2013.11.029

Accepted Manuscript
Novel pyrazole integrated 1,3,4-oxadiazoles: Synthesis, characterization and
antimicrobial evaluation
Srikantamurthy Ningaiah, Umesha K. Bhadraiah, Shridevi D. Doddaramappa,
Shubakara Keshavamurthy, Chethan Javarasetty
PII:
S0960-894X(13)01308-5
DOI:
http://dx.doi.org/10.1016/j.bmcl.2013.11.029
BMCL 21056
Reference:
Bioorganic & Medicinal Chemistry Letters
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Received Date:
Revised Date:
Accepted Date:
14 September 2013
4 November 2013
12 November 2013
Please cite this article as: Ningaiah, S., Bhadraiah, U.K., Doddaramappa, S.D., Keshavamurthy, S., Javarasetty, C.,
Novel pyrazole integrated 1,3,4-oxadiazoles: Synthesis, characterization and antimicrobial evaluation, Bioorganic
& Medicinal Chemistry Letters (2013), doi: http://dx.doi.org/10.1016/j.bmcl.2013.11.029
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Graphical Abstract
Novel pyrazole integrated 1,3,4-oxadiazoles:
Synthesis, characterization and
antimicrobial evaluation
Leave this area blank for abstract info.
Srikantamurthy Ningaiaha, Umesha K. Bhadraiaha,*, Shridevi D. Doddaramappab, Shubakara Keshavamurthya
and Chethan Javarasettyc
aDepartment of Chemistry, Yuvaraja’s College, University of Mysore, Mysore570005,
bDepartment of Studies in Chemistry, Manasagangotri, University of Mysore,
cDepartment of Biotechnology, Manasagangotri, University of Mysore, Mysore-570 006. India

Bioorganic & Medicinal Chemistry Letters
journal homepage: www.elsevier.com
Novel pyrazole integrated 1,3,4-oxadiazoles: Synthesis, characterization and
antimicrobial evaluation
Srikantamurthy Ningaiaha, Umesha K. Bhadraiaha,, Shridevi D. Doddaramappab, Shubakara
Keshavamurthya and Chethan Javarasettyc
a Department of Chemistry, Yuvaraja’s College, University of Mysore, Mysore-570 005.
bDepartment of Studies in Chemistry, Manasagangotri, University of Mysore,
cDepartment of Biotechnology, Manasagangotri, University of Mysore, Mysore-570 006. India.
ARTICLE INFO
ABSTRACT
Article history:
Received
Revised
Accepted
Available online
A novel series of 2-(5-methyl-1,3-diphenyl-1H-pyrazol-4-yl)-5-phenyl-1,3,4-oxadiazoles 7(a-m)
were synthesized either by cyclization of N'-benzoyl-5-methyl-1,3-diphenyl-1H-pyrazole-4-
carbohydrazide 4a using POCl3 at 120 °C or by oxidative cyclization of hydrazones derived
from various arylaldehyde and (E)-N'-benzylidene-5-methyl-1,3-diphenyl-1H-pyrazole-4-
carbohydrazide 5(a-d) using chloramine-T as oxidant. Newly synthesized compounds were
1
characterized by analytical and spectral (IR, H NMR, 13C NMR and LC–MS) methods. The
Keywords:
Pyrazole
1,3,4-oxadiazoles
Chloramine-T
Antimicrobial activity
Minimum inhibitory concentration (MIC)
synthesized compounds were evaluated for their antimicrobial activity and were compared with
standard drugs. The compounds demonstrated potent to weak antimicrobial activity. Among the
synthesized compounds, compound 7m emerged as an effective antimicrobial agent, while
compounds 7d, 7f, 7i and 7l showed good to moderate activity. The minimum inhibitory
concentration of the compounds was in the range of 20–50μg mL–1 against bacteria and 25–55μg
mL–1 against fungi. The title compounds represent a novel class of potent antimicrobial agents.
2009 Elsevier Ltd. All rights reserved.
Pyrazole ring is a ubiquitous motif in biologically active
compounds and therefore represents an interesting template for
combinatorial1,2 as well as medicinal chemistry.3-5 Among the
pyrazole derivatives some compounds are broadly used as
insecticides (Fipronil-MB46030), selective COX-2 inhibitor
(Celecoxib-M01AH01), phosphodiesterase inhibitor (Sildenafil-
G04BE03), anorectic antiobesity drug (Rimonabant-A08AX01)
and non-steroidal anti-inflammatory drug (Lonazolac-
M01AB09).6-11
has resulted in morbidity and mortality from treatment failures
and increased health care costs.22 Thus, intense efforts in
antimicrobial drug discovery are still needed to develop more
promising, economical, and effective drugs for use in the clinical
arena.23
1,3,4-Oxadiazoles are an important class of heterocyclic
compounds12 with a wide range of biological activities such as
antimicrobial,13 anticancer,14 antiviral,15 antineoplastic,16 CNS
depressant17 and tyrosinase inhibitory activity.18 Further, 1,3,4-
oxadiazole heterocycles are very good bioisostere of amide and
ester functionalities with substantial improvement in biological
activity by participating in hydrogen bonding interactions with
different receptors.19,20 In addition to pharmacophores pyrazole or
1,3,4-oxadiazole, there are other factors which influences the
biological activity of the molecules. For instance, presence of
electron releasing or withdrawing substituents, H-bond accepting
or donating groups and presence of lipophilic groups etc.
Identification of novel structure leads that may be of use in
designing new, potent and broad spectrum antimicrobial agents
The incidence of microbial infections has increased
dramatically in recent years.21 Resistance to antimicrobial agents
———
* Corresponding author Tel.: +91 0821-2420398 E-mail address: kbu68umesha@rediffmail.com (U.K.B).

remains a major challenge for medicinal chemistry researchers.
In this view, the discovery of the natural 4-hydroxypyrazole C-
glycoside antibiotic pyrazofurin (Fig. 1); has provided a basis for
more rationale design and synthesis of new pyrazoles as potential
antimicrobial.24-26 Consequently, several pyrazole derivatives that
exhibited antimicrobial activity were reported.27-29 However, a
survey of the literature revealed that linked biheterocyclic
compounds containing pyrazole to possess biological activity are
often reported. Recently pyrazole incorporated thiazole,30
characteristic absorption band at 1640 cm-1 and 3217 cm-1 due to
carbonyl and NH functional groups, respectively. The IR spectra
of all other synthesized compounds showed characteristic signals
at 1640-1595 cm-1 for (C═N), 1570-1460 cm-1 for (C═C), 1260-
1285 cm-1 for (CN), and 1240-1230 cm-1 for (CO).
1
The H NMR spectra of the compound 2a showed singlet due
to OH of pyrazole-4-carboxylic acid at δ 12.44 and also
disappearance of peaks at δ 1.15 (3H, t), and 4.13 (2H, q) due to
–CH2CH3 and –OCH2– protons respectively confirms the
formation of product 2a. Similarly the disappearance of broad
singlet due to NH at δ 9.69 and due to NH2 proton at δ 9.72 of
compounds 4 and 5 confirms the formation of cyclised
biheterocycle 7(a-m). In 13C NMR spectra, absence of peak at δ
166.2 and 168.4 due to carbonyl group (C═O) of 4 and 5
substantiated the formation of compounds 7(a-m). The mass
spectrum of all the compounds showed molecular ion peak at
M+1 corresponding to its molecular formula, which confirmed its
chemical structure.
thiadiazole,31
1,2,4-oxadiazole,32
1,2,4-triazoles
and
benzoxazoles,33 were synthesized and observed in the
enhancement of pharmacological effect. Also several biologically
active pyrazolyl-1,3,4-oxadiazole analogues have been reported
(Figure 1; A, B, C and D).34-40
Encouraged by these observations and in continuation of our
research work on the synthesis of heterocyclic compounds
containing multi-structure for biological activity,41 we thought of
synthesizing a new class of heterocycles, wherein potent 1,3,4-
oxadiazole moiety is linked to pyrazole moiety at C-4 position to
see the additive effect of these rings towards the antimicrobial
activity, which is the current passion being accomplished in most
of the drug discoveries.
Initially we have followed method A for the synthesis of 7a
where, the pyrazole acid 2a formed was treated with
benzohydrazide 3a in presence of coupling reagent EDC.HCl and
HOBt in dichloromethane at 0-25°C for 8 to 12h to get N'-
benzoyl-5-methyl-1,3-diphenyl-1H-pyrazole-4-carbohydrazide
4a in 72% yield after chromatographic separation. Then 4a was
heated to 120°C in presence of POCl3 yielded 2-(5-methyl-1,3-
diphenyl-1H-pyrazol-4-yl)-5-phenyl-1,3,4-oxadiazole 7a in 64%
yield. With this procedure the overall yield of the reaction was
46%. The low yield observed with method A was improved using
method B where, the compounds 1(a-d) were treated with
NH2NH2 in refluxing EtOH for about 2 to 4h. After the reaction
goes to completion (monitored through thin layer
chromatography), the compounds 5(a-d) thus obtained were
taken for the next step without isolation. In the next step the
compounds 5(a-d) were treated with various aryl aldehydes 6(a-
d) followed by oxidative cyclization in presence of chloramine-T
in refluxing EtOH for 2h yielded the corresponding 7(a-m) in
good to excellent yield. Good yield was accompanied with the
shorter reaction time and was attributed to the single chemical
transformation.
The synthesis of our desired pyrazole integrated 1,3,4-
oxadiazole derivatives began with ethyl 5-methyl-1,3-diphenyl-
1H-pyrazole-4-carboxylate42 1(a-d) as starting material. The two
All the synthesized compounds 2a, 4a, 5a and 7(a-m) were
tested in vitro for their antimicrobial activity against Bacillus
cereus (MTCC 8372), Staphylococcus aureus (MTCC 96),
(gram-positive bacteria), Escheria coli (MTCC 724), Klebsiella
pneumonia (MTCC 3384), (gram-negative bacteria) and four
fungi Aspergillus flavus (MTCC 873), Aspergillus niger (MTCC
281), Fusarium oxysporum (MTCC 284), Fusarium monaliforme
(MTCC 156) by disc diffusion43 and microdilution method.44 The
antibiotic Tetracycline and Nystatin are used as reference
antibacterial and antifungal substances, respectively for
comparison. In all the determinations tests were performed in six
replicate and the results were taken as a mean of at least three
determinations.
reactions sequence (method
biheterocycle 2-(5-methyl-1,3-diphenyl-1H-pyrazol-4-yl)-5-
phenyl-1,3,4-oxadiazoles 7(a-m) are depicted in Scheme 1. The
key intermediates 5-methyl-1,3-diphenyl-1H-pyrazole-4-
A & B) of preparing the
carboxylic acid 2a and 5-methyl-1,3-diphenyl-1H-pyrazole-4-
carbohydrazides 5(a-d) were synthesized by simple procedure
that involves reacting ethyl 5-methyl-1,3-diphenyl-1H-pyrazole-
4-carboxylate 1(a-d) with 10% NaOH solution in refluxing
MeOH for 4h followed by acidification with dilute hydrochloric
acid and by treating 1(a-d) with hydrazine hydrate in refluxing
EtOH for 2h respectively. Finally the products 7(a-m) were
achieved either by sequential transformation that involves
reaction of 2a with benzohydrazide 3a in presence of peptide
coupling reagent EDC.HCl in dichloromethane resulted N'-
benzoyl-5-methyl-1,3-diphenyl-1H-pyrazole-4-carbohydrazide
4a which, when heated with phosphorousoxychloride at 120°C,
gave the respective title compound 7a in moderate yield. On the
other hand, condensing the hydrazides 5(a-d) with a variety of
aryl aldehydes 6(a-d) followed by oxidative cyclization in
presence of chloramine-T yielded the corresponding 7(a-m) in
good quality and yield.
The results are summarized in Table 1-3. The results revealed
that, compounds 7d, 7f, 7i and 7l exhibited good to potent
antimicrobial activity. Of the five tested bacterial strains, gram-
positive bacteria were inhibited mostly by compounds 7d, 7l and
7f which contains NO2 and –OCH3 group on the phenyl ring,
which in turn is linked to C3 of the pyrazole moiety. While the
gram-negative bacteria were inhibited by compound 7j which
contains –OCH3 group on the phenyl ring, which in turn is linked
to C5 of the oxadiazole moiety. Compound 7m showed excellent
antimicrobial activity against all the tested strains of microbes
this may be due to the presence of –OCH3 group on the phenyl
ring of both the pyrazole as well as oxadiazole moieties. In
The structures of newly synthesized compounds 2a, 4a, 5(a-d)
and 7(a-m) were confirmed by their analytical and other spectral
data. The IR spectra of the compounds 4a and 5(a-d) exhibited

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Acknowledgments
Authors are thankful to Dr. K. Yeshoda Nanjappa Assistant
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Tables
Novel pyrazole integrated 1,3,4-oxadiazoles: Synthesis, characterization and antimicrobial evaluation
Srikantamurthy Ningaiaha, Umesha K. Bhadraiaha,, Shridevi D. Doddaramappab, Shubakara Keshavamurthya and Chethan
Javarasettyc
a Department of Chemistry, Yuvaraja’s College, University of Mysore, Mysore-570 005.
bDepartment of Studies in Chemistry, Manasagangotri, University of Mysore,
cDepartment of Biotechnology, Manasagangotri, University of Mysore, Mysore-570 006. India.
Table 1. Inhibitory zone (diameter) mm of synthesized compounds against tested bacterial strains
Antibacterial activity
Compounds
Ar1
Ar2
Gram positive
Gram negative
K. pneumonia
B. cereus
50 µg/ml 100 µg/ml
S. aureus
E. coli
50 µg/ml 100 µg/ml
50 µg/ml
100 µg/ml
± SD
50 µg/ml
100 µg/ml
± SD
± SD
± SD
± SD
± SD
± SD
± SD
2a
4a
5a
7a
7b
7c
7d
7e
7f
C6H5
C6H5
C6H5
C6H5
04 ± 0.11
08 ± 0.16
04 ± 0.12
05 ± 0.03
06 ± 0.11
04 ± 0.09
14 ± 0.10
08 ± 0.15
11 ± 0.03
04 ± 0.11
05 ± 0.15
06 ± 0.18
04 ± 0.11
06 ± 0.06
08 ± 0.23
16 ± 0.17
06 ± 0.20
09 ± 0.20
10 ± 0.11
09 ± 0.25
20 ± 0.21
16 ± 0.11
22 ± 0.10
08 ± 0.13
12 ± 0.19
14 ± 0.08
13 ± 0.22
10 ± 0.10
02 ± 0.03
06 ± 0.18
02 ± 0.12
06 ± 0.11
05 ± 0.16
04 ± 0.17
10 ± 0.13
06 ± 0.22
10 ± 0.04
05 ± 0.45
06 ± 0.26
05± 0.12
05 ± 0.19
06 ± 0.35
08 ± 0.26
18 ± 0.11
09 ± 0.15
07 ± 0.13
10 ± 0.13
08 ± 0.24
18 ± 0.06
13 ± 0.17
26 ± 0.10
10 ± 0.10
12 ± 0.20
10 ± 0.22
12 ± 0.14
12 ± 0.10
03 ± 0.05
13 ± 0.15
09 ± 0.13
05 ± 0.04
11 ± 0.11
08 ± 0.25
09 ± 0.23
14 ± 0.11
12 ± 0.15
10 ± 0.11
08 ± 0.32
11 ± 0.18
20± 0.22
10 ± 0.20
08 ± 0.18
18 ± 0.10
11 ± 0.11
06 ± 0.10
18 ± 0.23
14 ± 0.12
18 ± 0.09
20 ± 0.12
17 ± 0.12
12 ± 0.12
12 ± 0.13
20 ± 0.17
32 ± 0.19
16 ± 0.11
04± 0.11
08± 0.21
05± 0.09
06 ± 0.30
05± 0.10
04 ± 0.11
09 ± 0.52
06 ± 0.18
06 ± 0.11
06 ± 0.10
09 ± 0.12
07 ± 0.22
10 ± 0.25
08 ± 0.31
06 ± 0.09
14 ± 0.03
08 ± 0.08
14 ± 0.18
09 ± 0.13
09 ± 0.19
12 ± 0.18
09 ± 0.15
10 ± 0.12
12 ± 0.21
11 ± 0.22
10 ± 0.11
20 ± 0.18
11 ± 0.11
C6H5
C6H5
C6H5
C6H5
4ClC6H4
4OCH3C6H4
4NO2C6H4
3,4(OCH3)2C6H3
3,4,5(OCH3)3C6H2
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
7g
7h
7i
4ClC6H4
4OCH3C6H4
4NO2C6H4
3,4,5(OCH3)3C6H2
4ClC6H4
C6H5
C6H5
7j
C6H5
7k
4ClC6H4
* Corresponding author Tel.: +91 0821-2420398 E-mail address: kbu68umesha@rediffmail.com (U.K.B).
1

7l
7m
4NO2C6H4
4NO2C6H4
14 ± 0.18
12 ± 0.08
10 ± 0.07
22 ± 0.08
23 ± 0.06
21± 0.11
12 ± 0.12
10 ± 0.10
09 ± 0.11
20 ± 0.22
24 ± 0.11
20 ± 0.10
12 ± 0.15
21 ± 0.11
18 ± 0.14
22 ± 0.17
36 ± 0.12
30 ± 0.16
08 ± 0.40
11 ± 0.17
12 ± 0.12
16 ± 0.16
21 ± 0.21
20 ± 0.19
3,4,5(OCH3)3C6H2
3,4,5(OCH3)3C6H2
Tetracycline
a Zone of inhibition (Mean six replicate ± standard deviation).
Table 2. Inhibitory zone (diameter) mm of synthesized compounds against tested fungal strains
Antifungal activity
Compounds
A. flavus
A. niger
100 µg/ml
F oxysporum
F monaliforme
50 µg/ml 100 µg/ml
50 µg/ml
100 µg/ml
± SD
50 µg/ml
± SD
50 µg/ml
100 µg/ml
± SD
± SD
± SD
± SD
± SD
± SD
2a
4a
05± 0.12
10 ± 0.11
02 ± 0.17
04 ± 0.13
06 ± 0.11
02 ± 0.19
06 ± 0.12
05 ± 0.05
06 ± 0.09
14 ± 0.11
08 ± 0.12
03 ± 0.18
04 ± 0.15
14 ± 0.06
08 ± 0.08
18 ± 0.13
16 ± 0.07
08 ± 0.13
12 ± 0.21
06 ± 0.22
08 ± 0.27
10 ± 0.12
08 ± 0.25
14 ± 0.21
08 ± 0.18
12 ± 0.12
16 ± 0.13
14 ± 0.12
12 ± 0.17
13 ± 0.21
18 ± 0.21
11 ± 0.14
23 ± 0.02
20 ± 0.10
04 ± 0.15
08 ± 0.16
02 ± 0.18
05 ± 0.13
08 ± 0.16
02 ± 0.11
08 ± 0.13
03 ± 0.22
10 ± 0.04
09 ± 0.42
06 ± 0.35
02 ± 0.52
05 ± 0.19
14 ± 0.35
06 ± 0.22
11 ± 0.45
10 ± 0.05
06± 0.18
14 ± 0.13
08 ± 0.16
08 ± 0.16
10 ± 0.17
06 ± 0.28
12 ± 0.16
11 ± 0.17
20 ± 0.19
24 ± 0.10
12 ± 0.20
11 ± 0.41
12 ± 0.12
26 ± 0.10
14 ± 0.16
25 ± 0.14
25 ± 0.12
03 ± 0.11
08 ± 0.18
03 ± 0.15
03 ± 0.16
14 ± 0.17
04 ± 0.21
08 ± 0.23
15 ± 0.17
08 ± 0.15
04 ± 0.11
08 ± 0.20
06 ± 0.18
08 ± 0.22
15 ± 0.20
08 ± 0.15
14 ± 0.11
16 ± 0.04
05 ± 0.13
10 ± 0.16
08 ± 0.12
08 ± 0.17
22 ± 0.23
06 ± 0.22
10 ± 0.09
24 ± 0.11
10 ± 0.14
08 ± 0.18
12 ± 0.13
08 ± 0.28
10 ± 0.12
28 ± 0.11
16 ± 0.12
21 ± 0.12
30 ± 0.06
06± 0.20
06± 0.28
04± 0.22
04± 0.22
05± 0.17
03 ± 0.13
05 ± 0.51
06 ± 0.15
05 ± 0.13
06 ± 0.10
09 ± 0.18
06 ± 0.33
07 ± 0.25
10 ± 0.33
08 ± 0.40
12 ± 0.17
12 ± 0.18
05 ± 0.13
09 ± 0.09
06 ± 0.38
06 ± 0.08
08 ± 0.11
06 ± 0.19
14 ± 0.18
08 ± 0.13
10 ± 0.12
08 ± 0.23
11 ± 0.26
08 ± 0.22
10 ± 0.13
19 ± 0.11
18 ± 0.16
22 ± 0.21
28 ± 0.09
5a
7a
7b
7c
7d
7e
7f
7g
7h
7i
7j
7k
7l
7m
Nystatin
a Zone of inhibition (Mean six replicate ± standard deviation).
2

Table 3. The minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC) and minimal fungicidal concentration
(MFC) in µg/mL of synthesized compounds against tested strains
Antibacterial activity
Antifungal activity
Compounds
Gram positive
B. cereus S. aureus
Gram negative
K. pneumonia
E. coli
MBC
A. flavus
MIC
F. oxysporum
F. monaliforme
MIC
30
25
40
35
40
50
20
35
20
40
35
25
35
40
20
20
4
MBC
250
180
260
230
240
240
150
230
160
240
220
200
230
260
160
160
120
---
MIC
40
25
40
35
50
40
20
40
20
45
35
25
40
40
20
20
10
---
MBC
250
200
250
240
250
240
150
235
155
250
225
190
250
250
155
150
120
---
MIC
35
25
35
40
40
35
25
35
25
35
45
25
20
45
25
20
12
---
MIC
30
25
35
30
50
35
25
35
25
30
45
25
20
50
25
20
8
MBC
240
200
230
220
250
260
180
250
175
220
240
185
160
250
170
155
120
---
MFC
300
275
275
280
275
270
290
275
275
230
270
290
275
210
275
215
---
MIC
55
40
45
50
30
40
40
25
40
40
50
40
40
30
50
25
---
15
MFC
295
260
270
275
215
280
280
220
290
275
280
275
275
215
280
220
---
MIC
45
50
50
55
40
40
45
55
55
55
50
50
55
25
55
25
---
12
MFC
270
260
280
290
270
290
275
290
300
300
290
290
300
215
290
225
---
2a
280
190
240
260
250
240
190
220
170
235
235
180
150
245
175
150
120
---
55
50
40
40
50
50
50
45
45
30
45
55
45
25
40
30
---
08
4a
5a
7a
7b
7c
7d
7e
7f
7g
7h
7i
7j
7k
7l
7m
Tetracycline
Nystatin
---
---
100
100
100
a (Mean six replicate ± standard deviation).
3

Figure and Scheme
Synthesis, characterization and antimicrobial evaluation of novel
pyrazole integrated 1,3,4-oxadiazoles
Ningaiah Srikantamurthya, Kumbarandoddi B. Umeshaa,, Keshavamurthy Shubakaraa and
Javarasetty Chethanb
a Department of Chemistry, Yuvaraja’s College, University of Mysore, Mysore-570 005.
bDepartment of Biotechnology, Manasagangotri, University of Mysore, Mysore-570 005. India.
 Corresponding author. Tel.: +91 9480477620; fax: +91-821- 2419292; e-mail: kbu68umesha@rediffmail.com (KBU),
orgchemsri@gmail.com (NS).
1

2

Graphical Abstract
Leave this area blank for abstract info.
Novel pyrazole integrated 1,3,4-oxadiazoles:
Synthesis, characterization and
antimicrobial evaluation
Srikantamurthy Ningaiaha, Umesha K. Bhadraiaha,*, Shridevi D. Doddaramappab, Shubakara Keshavamurthya
and Chethan Javarasettyc
aDepartment of Chemistry, Yuvaraja’s College, University of Mysore, Mysore570005,
bDepartment of Studies in Chemistry, Manasagangotri, University of Mysore,
cDepartment of Biotechnology, Manasagangotri, University of Mysore, Mysore-570
006. India