Design, synthesis and biological evaluation of 1,3,4-oxadiazole derivatives

Article abstract of DOI:10.1016/j.ejmech.2010.08.003

3D QSAR analysis for the 21 molecules of 1,3,4-oxadiazoles was carried out by using k-Nearest Neighbor Molecular Field Analysis (kNN-MFA) combined with various selection procedures. 30 3D QSAR models were generated; one of these models was selected on the basis of q² and pred-r² values. The selected Model has training set of 17 molecules and test set of 4 molecules with validation (q²) and cross validation (pred-r²) values of 0.6969 and 0.6148 respectively. Title compounds of 1,3,4-oxadiazole derivatives were synthesized by the ring closure reactions of various acylhydrazides with carbon disulphide (4a-e) and with aromatic acids in POCl₃ (5a-e). After structural elucidation, all the synthesized compounds were evaluated for their antimicrobial activity against Escherichia coli, Staphylococcus aureus and Staphylococcus epidermidis.

Full text of DOI:10.1016/j.ejmech.2010.08.003

European Journal of Medicinal Chemistry 45 (2010) 4963e4967
Contents lists available at ScienceDirect
European Journal of Medicinal Chemistry
journal homepage: http://www.elsevier.com/locate/ejmech
Original article
Design, synthesis and biological evaluation of 1,3,4-oxadiazole derivatives
,
c
d
a
Keshari Kishore Jha a, Abdul Samad b , Yatendra Kumar , Mohd. Shaharyar , Ratan Lal Khosa ,
*
Jainendra Jain a, Vikash Kumar e, Priyanka Singh f
a Department of Pharmaceutical Technology, MIET, Meerut, U.P, India
b Department of Pharmaceutical Chemistry, College of Pharmacy in Al-Kharj, King Saud University, Riyadh, Saudi Arabia
c I.T.S. Paramedical College, Muradnagar, Ghaziabad, U.P, India
d Faculty of Pharmacy, Jamia Hamdard, New Delhi, India
e P.D.M College of Pharmacy, Bahadurgarh, Haryana, India
f Department of Pharmacy, SITM, Barabanki, U.P, India
a r t i c l e i n f o
a b s t r a c t
Article history:
3D QSAR analysis for the 21 molecules of 1,3,4-oxadiazoles was carried out by using k-Nearest Neighbor
Molecular Field Analysis (kNN-MFA) combined with various selection procedures. 30 3D QSAR models
were generated; one of these models was selected on the basis of q2 and pred_r2 values. The selected
Model has training set of 17 molecules and test set of 4 molecules with validation (q2) and cross vali-
dation (pred_r2) values of 0.6969 and 0.6148 respectively.
Received 17 December 2008
Received in revised form
4 June 2010
Accepted 2 August 2010
Available online 12 August 2010
Title compounds of 1,3,4-oxadiazole derivatives were synthesized by the ring closure reactions of
various acylhydrazides with carbon disulphide (4aee) and with aromatic acids in POCl3 (5aee). After
structural elucidation, all the synthesized compounds were evaluated for their antimicrobial activity
against Escherichia coli, Staphylococcus aureus and Staphylococcus epidermidis.
Keywords:
1,3,4-Oxadiazole
Antimicrobial activity
3D QSAR
Ó 2010 Elsevier Masson SAS. All rights reserved.
kNN-MFA
1. Introduction
consider more general biological applications. Especially, González-
Díaz et al. extended these representations to the study of protein
The literature is flooded with reports of a variety of biological
activities of substituted-1,3,4-oxadiazoles. These include anti-
inflammatory [1e4], hypoglycemic [5,6], antianxiety, antidepres-
sant [7], and antimitotic [8] activities. In addition to these,
a number of researchers have reported antimicrobial activities
[9e13]. Keeping these above facts in view we considered it of
interest to carry out 3D QSAR studies and synthesize a few 2,5-
disubstituted-1,3,4-oxadiazoles for their antimicrobial evaluation.
The computer-aided predictionof biological activity in relation to
the chemical structure of a compound is now a commonly used
technique in drug discovery[14e17]. Inparticular QSAR modelshave
been successfully applied to predict antibacterial drugs [18e21].
Recently various QSARapproaches have been introduced in the form
of Topological Indices (TIs) or Connectivity Indices (CIs) or simply
invariants of a molecular graph, whose vertices are atoms, nucleo-
tides, oramino acidslabeledwith physicochemical properties (mass,
polarity, electronegativity, and charge). Parameters like numerical
indices, topological indices are the recent outcome of these tech-
niques, when applied to proteins, viral surfaces, RNA secondary
structures and small molecules [22e27] have extended the scope to
sequences [28] and Mass Spectra outcomes of proteins and/or
protein serum profiles in parasites [29], Toxicoproteomics and
diagnosis of cancer patients [30,31]. Also, these descriptors can be
used in QSAR studies of biological entity at molecular level. Various
QSAR Models have been reported to be an efficient tool for compu-
tational assembly of DrugeBacterial Complex Networks that accu-
rately reproduce the network based on experimental findings [32].
In this study we report our efforts to relate the dependence of
the antimicrobial activity of new compounds on the nature of
substitution in the 2,5-disustituted-1, 3, 4-oxadiazoles by using
electronic and stearic descriptors. The present 3D QSAR study was
carried out by using k-Nearest Neighbor Molecular Field Analysis
(K-NNMFA) method for rationalizing the synthetic scheme. The
better the description of a molecule in terms of structural param-
eters representing its activity, the better the results of pattern
recognition and separation of molecules by activity.
2. Results and discussion
2.1. Designing analysis
The importance and utility of the new 3D QSAR method i.e. kNN-
MFA has been established by applying it to known sets of molecules
* Corresponding author. Tel.: þ966 534503120.
E-mail address: samadpharmacist@gmail.com (A. Samad).
0223-5234/$ e see front matter Ó 2010 Elsevier Masson SAS. All rights reserved.
doi:10.1016/j.ejmech.2010.08.003

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K.K. Jha et al. / European Journal of Medicinal Chemistry 45 (2010) 4963e4967
Table 1
Model summary.
COOH
4 SPH GEN VC3
Training set size ¼ 17
Test set size ¼ 4
Selected descriptors:
E_347
(1a-d)
R
H2SO4
C2H5OH
E_1503
S_2472
Statistics:
COOC2H5
k-Nearest Neighbour ¼ 2
n ¼ 17
Degree of freedom ¼ 13
q2 ¼ 0.6969
R
(2a-d)
NH2.NH2.H2O
q2_se ¼ 3.2732
Pred r2 ¼ 0.6148
pred_r2se ¼ 2.9017
Descriptor range:
E_347
E_1503
S_2472
0.1634
5.5752
ꢀ0.0068
0.3100
5.9369
ꢀ0.0046
CONHNH2
R
(3a-d)
CS2/KOH
R`COOH
as described above. We report that 30, 3D QSAR models were
generated by kNN-MFA in conjunction with Simulated Annealing
(SA), Genetic Algorithms & Stepwise (SW) Forward Backward selec-
tion method. From these models, two of them were having good q2 &
pred_r2 values, one of which was selected having good internal and
external predictivity. For this model training and test sets were
selected using random selection method and the descriptors were
selected using simulated annealing method. The summary of the
selected model (Table 1) can be given as: k ¼ 2; q2 ¼ 0.6969; pre-
d_r2 ¼ 0.6148; Descriptor range: E_34: 7 0.1634e0.3100; E_1503:
5.5752e5.9369; S_2472: ꢀ0.0068 to ꢀ0.0046.
N
N
N
N
SH
O
O
R
R1
R
(5a-e)
(4a-e)
Fig. 2. Scheme.
Descriptor range (as shown in Fig. 1) for the selected model of
the Series elaborates that; (i) 1, 3, 4-oxadiazole ring is essential for
the activity. (ii) Negative range of steric field indicates that less
bulky substituent would be favourable for the activity. (iii) Positive
range of electronic field indicates that less electronegative
substituent would be favourable for the activity as already the basic
moiety taken in the study is substituted with high electronegative
groups like chlorine and fluorine so the other substituents
employed should be less electronegative.
(3aed) with carbon disulphide (4aee) or with aromatic acids in
POCl3 (5aee) in good quality and yield. The Aroylhydrazides (3aed)
were synthesized by esterification reaction of various aromatic
acids by using sulphuric acid as catalyst. The synthesized 1,3,4-
oxadiazoles were characterized by IR, 1H NMR, mass and elemental
analysis. The IR spectrum of final compounds showed the absence
of amide and carbonyl frequency in the region 1760e1650 cmꢀ1
and the NH frequency in the region 3400e3200 cmꢀ1 and showed
a new peak at 1620e15640 cmꢀ1 due to C]N frequency.
2.2. Chemistry
2.3. Antimicrobial activity
As shown in Scheme (Fig. 2), the title compounds were
synthesized by the ring closure reactions of various aroylhydrazides
The newly prepared compounds were screened for their anti-
bacterial activity against Escherichia coli (MTCC 443), Staphylo-
coccus epidermidis (ATCC12228) and Staphylococcus aureus
(ATCC25923) bacterial strains by disc diffusion method. In all the
determinations tests were performed in triplicate and the results
were taken as a mean of three determinations. The compounds 4b,
4e and 5e have shown significant inhibition comparable to stan-
dard while compound 5a and 5c have shown moderate activity.
3. Conclusion
The 3D QSAR study has shown that less electronegative
substituent would be favourable for the activity. As already the
basic moiety taken in the study is substituted with high electro-
negative groups like chlorine and fluorine so the other substituents
employed should be less electronegative. Hence the future mole-
cules should be designed with less electronegative group to result
in potentially active molecules. We have synthesized 2,5-disubsti-
tuted-1,3,4-oxadiazole derivatives and evaluated for their antimi-
crobial activities. The compounds 4b, 4e and 5e have shown
significant inhibition comparable to standard while compound 5a
and 5c have shown moderate activity.
Fig. 1. Show points for the molecules.

K.K. Jha et al. / European Journal of Medicinal Chemistry 45 (2010) 4963e4967
4965
4. Experimental protocols
4.1. Designing methodology
The in vitro minimum inhibitory concentration in mcg per ml
of various 2,5-disubstituted-1, 3, 4-oxadiazoles against E. coli
MTCC 443 strain by microdilution method was taken from the
literature [33,34]. To these values, we have applied one of the
modest kNN-MFA with various variable selection methods.
Similar to many 3D QSAR methods [35,36] kNN-MFA requires
suitable alignment of set of molecule. This is followed by gener-
ation of common rectangular grid around the molecules. The
steric and electrostatic energies are computed at the lattice point
of grid using methyl probe of charge þ1, these interaction energy
values at the grid point are considered for relationship generation
using kNN method and utilized as descriptors to decide nearness
between molecules.
All the 21 molecules taken in the study (Table 2) were drawn in
Vlife QSAR Plus. They were optimized by using “Merck Molecular
Force Field (MMFF)” and they were batch optimized also. After this
all the 21 molecules were aligned (Fig. 3) using template based
alignment method by choosing a minimum common structure as
‘Template’ (Fig. 4) and the most effective one as the ‘Reference
Molecule’ (Fig. 5). From the 21 molecules taken in the study,
a training set of 17 molecules and test set of 4 molecules were
generated using the various selection procedures. After the selec-
tion of the test and training sets, kNN methodology was applied to
the descriptors generated over the grid as shown in the ‘Show
Point’ (Fig. 1).
Fig. 3. Alignments of 21 molecules.
4.2. Chemistry
Melting points of the synthesized compounds were taken by
one end open capillary tubes melting point apparatus and are
uncorrected. Infra Red (IR) spectra were recorded on Shimadzu FTIR
8400S spectrophotometer (KBr) and 1H NMR spectra in DMSO-d6
and chloroform on Brucker DRX ꢀ300 MHz and 400 MHZ using
TMS as internal standard. Chemical shifts were reported in parts
per million (PPM) The homogeneity of the synthesized compounds
was monitored by ascending thin layer chromatography (TLC) on
silica gel G plates and visualized by using Iodine vapour. Developing
solvents were chloroform:methanol (4:1).
The QSAR models were evaluated using following statistical
measures: n e number of descriptors; k e number of nearest
neighbors; q2 e cross validated r2 (by leave-one-out method);
pred_r2 e predicted r2 for the external test.
4.2.1. General procedure for the preparation of acid hydrazides
(3aed)
The appropriate aromatic acids (0.01 mol) were dissolved in
absolute ethanol (10 ml). Hydrazine hydrate (0.02 mol) and few
drops of conc. sulphuric acid were added. The reaction mixture
was refluxed for 6 h. The resulting solid obtained was filtered,
dried and crystallized from methanol. The completion of reaction
was monitored by Thin Layer Chromatography and Infrared
Spectrophotometer. (3a: Salicylic acid hydrazide; 3b: Bezoic acid
hydrazide; 3c: p-toluic acid hydrazide; 3d: Isonicotinic acid
hydrazide).
Table 2
Structures of the molecules for 3d QSAR studies.
N
N
F
H3C
N
N
R
O
R
O
N
Cl
O
Cl
Compound 1-10
Compound 11-21
4.2.2. General procedure for the preparation of 5-(substituted)-2-
thio-1,3,4-oxadiazoles (4aee)
Compound
R
To a solution of the hydrazides (0.01 mol) in ethanol (15 ml) at
0 ꢁC, carbon disulphide (2 ml) and potassium hydroxide (0.6 g)
were added, and the reaction mixture was refluxed until the
evolution of H2S gas ceased (around 12 h). Excess solvents were
evaporated under reduced pressure and the residue was dissolved
in water and then acidified with dilute hydrochloric acid (10%) to
pH w5. The precipitate was filtered off, dried, and crystallized from
1
2
3
4
5
6
7
8
C6H5e
4-OMeeC6H4e
4-CleC6H4e
2,4-Cl2eC6H3e
2,4-Cl2e5FeC6H2e
4-CleC6H4OCH2e
2,4-Cl2eC6H3OCH2e
4-Fe3-(OC6H5)eC6H3e
9
5-(3-Cle4-FeC6H3)-2-furanyl-
5-(2-Cle4-FeC6H3)-2-furanyl-
C6H5e
10
11
12
13
14
15
16
17
18
19
20
21
4-CleC6H4e
N
N
2,3-Cl2eC6H3e
2,4-Cl2eC6H3e
4-OMeeC6H4e
4-NO2eC6H4e
2-NO2eC6H4e
4-MeeC6H4e
2-MeeC6H4e
Pyridin-3-yl-
Pyridin-4-yl-
O
Fig. 4. Templates.

4966
K.K. Jha et al. / European Journal of Medicinal Chemistry 45 (2010) 4963e4967
room temp for overnight. The mixture was poured into cold water,
N
N
filtered, dried and crystallized from ethanol. The completion of
reaction was monitored by Thin Layer Chromatography and
Infrared Spectrophotometer.
O
H3C
O
N
Cl
Cl
4.2.3.1. Compound 4b: 2-(5-sulfanyl-1,3,4-oxadiazol-2-yl) phenyl-
acetate. Recrystallised from ethanol to yield 64%, m.p. 132ꢀ134 oC,
FTIR (KBr) cmꢀ1: 1751 (C]O),1610 (C]N, ring) 760 (CeOeC, ring),
Fig. 5. Reference molecule.
1080 (C]S), 1490 (C]C Ar). 1H NMR (DMSO-d6)
d: 2.43 (3H, m,
ethanol. The completion of reaction was monitored by Thin Layer
Chromatography and Infrared Spectrophotometer. Compound 4a,
4c, 4d, 4e were prepared with this method.
COCH3), 2.74 (1H, s, NH), 7.25 (1H, d, Ar H), 7.435 (1H, m, Ar H),
7.653 (1H, m, Ar H), 8.029 (1H, d, Ar H). MS 236. Anal. CHN: calcd C
50.84, H 3.41, N 11.86, found C 50.92, H 3.47, N 11.97.
4.2.2.1. Compound 4a: 2-(5-sulfanyl-1,3,4-oxadiazol-2-yl) phe-
nol. Recrystallised from ethanol to yield 79%, m.p. ꢀ205 ꢁC, FTIR
(KBr) cmꢀ1: 1612 (C]N, ring), 760 (CeOeC, ring), 1108(C]S), 1590
4.2.4. General procedure for the preparation of 3, 5-disubstituted-1,
3, 4-oxadiazoles (5aee)
The aromatic acid hydrazide (0.01 mol) and an appropriate
aromatic acid (0.01 mol) were refluxed in POCl3 (5 ml) for 8 h,
cooled and poured on to crushed ice, made basic with sodium
bicarbonate solution. The precipitate was filtered off, dried, and
crystallized from ethanol. The completion of reaction was moni-
tored by Thin Layer Chromatography and Infrared Spectropho-
tometer. Compounds 5aee were prepared with this method.
(C]C Ar), 3250 (CeOH Ar), 3350 (NH). 1H NMR (DMSO-d6)
d:
6.92e6.95 (1H, m), 7.01e7.03 (1H, d), 7.38e7.42 (1H, m), 7.60e7.63
(1H, d), 10.43 (1H, s, eOH), 14.56 (1H, broad s, eSH). MS 194. Anal.
CHN: calcd C 49.72, H 3.11, N 14.42, found C 49.76, H 3.16, N 14.49.
4.2.2.2. Compound 4c: 5-phenyl-1,3,4-oxadiazole-2-thiol. Recrystal-
lised from ethanol to yield 58%, m.p. ꢀ185 ꢁC, FTIR (KBr) cmꢀ1: 1610
(C]N, ring), 788 (CeOeC, ring), 1060(C]S), 1502 (C]C Ar). 1H
4.2.4.1. Compound 5a: 2-[5-(naphthalen-2-ylmethyl)-1,3,4-oxadia-
zol-2-yl] phenol. Recrystallised from ethanol to yield 80%,
m.p. ꢀ97 ꢁC, FTIR (KBr) cmꢀ1: 1600 (C]N, ring) 759 (CeOeC, ring),
NMR (DMSO-d6) d: 6.37e8.21 (5H, complex m, 5 Ar H), 14.138 (1H,
s, SH), 7.38e7.42 (1H, m), 7.60e7.63 (1H, d), 10.43 (1H, s, eOH),
14.56 (1H, broad s, eSH). MS 178. Anal. CHN: calcd C 53.92, H 3.39,
N 8.98, found C 54.01, H 3.45, N 15.78.
1055 (C]S), 1592 (C]C Ar). 1H NMR (DMSO-d6)
d: 2.50 (2H, s, CH2),
5.13(1H, s, OH), 6.94e8.19 (12H, m, 11Ar H, 1NH). MS 302. Anal.
CHN: calcd C 75.48, H 4.67, N 9.27, found C 75.55, H 4.70, N 9.38.
4.2.2.3. Compound 4d: 5-(4-methylphenyl)-1, 3, 4-oxadiazole-2-
thiol. Recrystallised from ethanol to yield 62%, m.p. ꢀ193 ꢁC, FTIR
(KBr) cmꢀ1: 1618 (C]N, ring), 750 (CeOeC, ring), 1072(C]S), 1510
4.2.4.2. Compound 5b: 2-[5-(4-methylphenyl)-1,3,4-oxadiazol-2-yl]
phenol. Recrystallised from methanol to yield 75%, m.p.156 ꢁC, FTIR
(KBr) cmꢀ1: 1614 (C]N, ring) 779 (CeOeC, ring), 1055 (C]S), 1480
(C]C Ar), 2947 (CeH), 3350 (NH). 1H NMR (DMSO-d6)
d: 3.39 (3H,
m, Ar CH3), 7.39e7.41 (2H, s, fine splitting, Ar H), 14.69 (1H, s, eSH).
MS 192. Anal. CHN: calcd C 56.23, H 4.19, N 14.57, found C 56.28, H
4.23, N 14.62.
(C]C Ar), 3363 (CeOH). 1H NMR (DMSO-d6)
d: 2.435 (3H, s, Ar CH3),
7.00e8.03(8H, Complex m, 8 Ar H), 10.20 (1H, s, Ar OH). MS 252.
Anal. CHN: calcd C 71.42, H 4.79, N 11.10, found C 71.58, H 4.88, N
11.17.
4.2.2.4. Compound 4e: 5-(pyridin-3-yl)-1, 3, 4-oxadiazole-2-
thiol. Recrystallised from ethanol to yield 71%, m.p. ꢀ169 ꢁC, FTIR
(KBr) cmꢀ1: 1635 (C]N, ring), 759 (CeOeC, ring), 1035(C]S), 1592
4.2.4.3. Compound 5c: 2-[5-(2-methylphenyl)-1,3,4-oxadiazol-2-yl]
phenol. Recrystallised from ethanol to yield 59%, m.p. 164 ꢁC, FTIR
(KBr) cmꢀ1: 1604 (C]N, ring) 781 (CeOeC, ring), 1553 (C]C Ar),
(C]C Ar). 1H NMR (DMSO-d6)
d: 2.46 (1H, m, NH), 7.76e7.78 (2H, s,
fine splitting), 8.76e8.77 (2H, s, fine splitting). MS 179. Anal. CHN:
calcd C 46.92, H 2.81, N 23.45, found C 47.01, H 2.86, N 23.50.
3330 (CeOH), 2921 (CeH). 1H NMR (DMSO-d6)
d: 2.79 (3H, s, Ar
CH3), 7.26e8.03(8H, Complex m, 8 Ar H), 10.59 (1H, s, Ar OH). MS
252. Anal. CHN: calcd C 71.42, H 4.79, N 11.10, found C 71.58, H 4.88,
N 11.17.
4.2.3. Synthesis of 2-(5-mercapto-1,3,4-oxadiazol-2-yl)
phenylacetate (4B): (acetylation of 4a)
The synthesized 2-(5-mercapto-1,3,4-oxadiazol-2-yl) phenol
(0.01 mol) was treated with acetic anhydride (5 ml) and kept at
4.2.4.4. Compound 5d: 2-(5-phenyl-1,3,4-oxadiazol-2-yl)phe-
nol. Recrystallised from methanol toyield60%, m.p.134e138 ꢁC, FTIR
(KBr) cmꢀ1: 1606 (C]N, ring) 781 (CeOeC, ring), 1548 (C]C Ar),
3060 (CeOH). 1H NMR (DMSO-d6)
d: 2.79 (3H, s, Ar CH3), 7.26e8.03
Table 3
(8H, Complex m, 8 Ar H), 10.59 (1H, s, Ar OH). MS. 238. Anal. CHN:
calcd C 70.58, H 4.23, N 11.76, found C 70.65, H 4.28, N 11.80.
Antibacterial Activity of the Compounds (4a-e) & (5a-e)
Zone of inhibition in (mm)a
4.2.4.5. Compound 5e: 3-(5-phenyl-1,3,4-oxadiazol-2-yl)pyr-
idine. Recrystallised from ethanol to yield 68%, m.p. 182e188 ꢁC,
FTIR (KBr) cmꢀ1: 1620 (C]N, ring) 772 (CeOeC, ring), 1552 (C]C
Strain
E. coli
S. epidermidis
S.aureus
Std(ciprofloxacin)
26
18
25
20
19
21
21
19
23
19
24
30
22
26
18
16
26
25
22
24
18
25
29
24
24
22
20
25
23
20
23
21
24
4a
4b
4c
4d
4e
5a
5b
5c
5d
5e
Ar), 3090 (CeOH). 1H NMR (DMSO-d6)
d: 2.46 (1H, m, NH),
7.76e7.78 (2H, s, fine splitting), 8.76e8.77 (2H, s, fine splitting),
10.59(1H, s, Ar OH). MS 239. Anal. CHN: calcd C 65.27, H 3.74, N
17.56, found C 65.30, H 3.85, N 17.68.
4.3. Microbiology
The compounds were tested against bacterial strains i.e. E. coli
(MTCC 443), S. epidermidis (ATCC12228) and S. aureus (ATCC25923).
a
Average of three determinations.

K.K. Jha et al. / European Journal of Medicinal Chemistry 45 (2010) 4963e4967
4967
A standard inoculum (1e2 ꢂ 107 c.f.u./ml 0.5 McFarland standards)
[37] was introduced on to the surface of sterile agar plates, and
a sterile glass spreader was used for even distribution of the inoc-
ulum. The discs measuring 6.25 mm in diameter were prepared
from Whatman no.1 filter paper and sterilized by dry heat at 140 ꢁC
for 1 h. The sterile discs previously soaked in a known concentra-
tion of the test compounds were placed in nutrient agar medium.
Solvent and growth controls were kept. The plates were inverted
and incubated for 24 h at 37 ꢁC. Ciprofloxacin was used as a stan-
dard drug. Inhibition zones were measured and compared with the
controls. The bacterial zones of inhibition values are given in Table
3. Minimum inhibitory concentrations (MICs) were determined by
broth dilution technique. The nutrient broth, which contained
logarithmic serially two fold diluted amount of test compound and
controls were inoculated with approximately 5 ꢂ105 c.f.u. of
actively dividing bacteria cells. The cultures were incubated for 24 h
at 37 ꢁC and the growth was monitored visually and spectropho-
tometrically. The lowest concentration (highest dilution) required
to arrest the growth of bacteria was regarded as minimum inhibi-
tory concentration (MIC).
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ꢀ
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Acknowledgement
The authors are grateful to Head, Department of Pharmaceutical
Technology for providing the vlife QSAR Plus Software and other
necessary facilities for carrying out the Research. We are also
grateful to Head, NMR Research Center, CDRI, and Lucknow for
providing 1H NMR and Mass spectral data.
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