Molecular properties prediction, synthesis and antimicrobial activity of some newer oxadiazole derivatives

Article abstract of DOI:10.1016/j.ejmech.2010.07.069

In present investigation a series of 28 oxadiazole analogues (AB1-AB28) were subjected to molecular properties prediction, drug-likeness by Molinspiration (Molinspiration, 2008) & MolSoft (MolSoft, 2007) softwares, lipophilicity and solubility parameters using ALOGPS 2.1 program. Out of 28 analogues only 16 were chosen on the basis of Lipinski Rule of Five (Ro5) for the synthesis and antimicrobial screening as oral bioavailable drugs/leads. Maximum drug-likeness model score (1.22) was found to be of compound AB13. Selected compounds (AB1-AB2), (AB5-AB9), (AB12-AB16), (AB18-AB21) were synthesized and characterized by IR, NMR and mass spectral analysis followed by antibacterial and antifungal screening. It was observed that compounds showed moderate to good antibacterial activity, but their antifungal activity was somewhat moderate. Compounds AB13 and AB20 showed pronounced activity against all bacterial and fungal strains. We had noticed that compounds (AB13, AB20) bearing OH group at one of the phenyl ring of oxadiazole exhibited good antimicrobial properties and their drug-likeness model score were also predicted maximum among the series.

Full text of DOI:10.1016/j.ejmech.2010.07.069

European Journal of Medicinal Chemistry 45 (2010) 5862e5869
Contents lists available at ScienceDirect
European Journal of Medicinal Chemistry
journal homepage: http://www.elsevier.com/locate/ejmech
Original article
Molecular properties prediction, synthesis and antimicrobial activity of some
newer oxadiazole derivatives
,
b
a
a
Mohammed Afroz Bakht a , M. Shahar Yar , Sami Gaber Abdel-Hamid , Saleh I. Al Qasoumi ,
*
Abdul Samad a
a Department of Pharmaceutical Chemistry, College of Pharmacy in Al-Kharj, King Saud University, P.O. Box 2457, Riyadh, Saudi Arabia
b Departments of Pharmaceutical Chemistry, Faculty of Pharmacy, Hamdard University, New Delhi 110062, India
a r t i c l e i n f o
a b s t r a c t
Article history:
In present investigation a series of 28 oxadiazole analogues (AB1eAB28) were subjected to molecular
properties prediction, drug-likeness by Molinspiration (Molinspiration, 2008) & MolSoft (MolSoft, 2007)
softwares, lipophilicity and solubility parameters using ALOGPS 2.1 program. Out of 28 analogues only 16
were chosen on the basis of Lipinski “Rule of Five” (Ro5) for the synthesis and antimicrobial screening as
oral bioavailable drugs/leads. Maximum drug-likeness model score (1.22) was found to be of compound
AB13. Selected compounds (AB1eAB2), (AB5eAB9), (AB12eAB16), (AB18eAB21) were synthesized and
characterized by IR, NMR and mass spectral analysis followed by antibacterial and antifungal screening. It
was observed that compounds showed moderate to good antibacterial activity, but their antifungal
activity was somewhat moderate. Compounds AB13 and AB20 showed pronounced activity against all
bacterial and fungal strains. We had noticed that compounds (AB13, AB20) bearing OH group at one of
the phenyl ring of oxadiazole exhibited good antimicrobial properties and their drug-likeness model
score were also predicted maximum among the series.
Received 8 April 2010
Received in revised form
1 July 2010
Accepted 2 July 2010
Available online 1 October 2010
Keywords:
1,3,4-Oxadiazole
Molecular properties prediction
Lipinski-Rule of 5
Drug-likeness
Antimicrobial screening
Ó 2010 Elsevier Masson SAS. All rights reserved.
1. Introduction
mask the side effects of carboxylic moiety we planned to synthesize
different 2,5-disubstituted-1,3,4-oxadiazoles via the condensation of
Antimicrobial agents are considered “miracle drugs” that are our
leading weapons in the treatment of infectious diseases. Antimicro-
bial resistance is the ability of certain microorganisms to withstand
attack by antimicrobials, and the uncontrolled rise in resistant
pathogens threatens lives and wastes limited healthcare resources.
Life-treating infectious diseases caused by multidrug-resistant
Gram-positive and Gram-negative pathogen bacteria increased an
alarming level around the world. Owing to this increased microbial
resistance, new classes of antibacterial agents with novel mecha-
nisms are crucial need to combat with the multidrug-resistant
infections. The widespread use of 1,3,4-oxadiazoles as a scaffold in
medicinal chemistry establishes this moiety as a member of the
privileged structures class [1]. 1,3,4-Oxadiazole ring is associated
with many types of biological properties such as anti-inflammatory
[2e4], hypoglycemic [5], antifungal, antibacterial [6e8] and insecti-
cidal [9,10] activities. The major side effects in the use of aryl alkanoic
acids is their gastric irritation, which is partly due to the corrosive
nature of carboxylic acid group present in them. In order to reduce or
appropriate acid hydrazides with various chalcones containing free
carboxylic acid group in presence of phosphorus oxychloride in the
hope of getting potent antimicrobial agents. In the development of
drugs intended for oral use, good drug absorption and appropriate
drug delivery are very important [11]. About 30% of oral drugs fail in
development due to poor pharmacokinetics [12]. Among the phar-
macokinetic properties, a low and highly variable bioavailability is
indeed the main reason for stopping furtherdevelopmentof the drug
[13]. Thus, predictions of bioavailability and bioavailability-related
properties, such as solubility, lipophilicity are important before
actual synthesis, in order to reduce enormous wastage of expensive
chemicals and precious time. An in silico model for predicting oral
bioavailability is very important, both in the early stage of drug
discovery to select the most promising compounds for further opti-
mization and in the later stage to identify candidates for further
clinical development [13]. In present investigation a series of 28
oxadiazole analogues (AB1eAB28) were subjected to molecular
properties prediction, drug-likeness by Molinspiration [32] & Mol-
Soft (MolSoft, 2007) softwares, lipophilicity and solubility parameter
by using ALOGPS 2.1 program to filter the compounds for further
synthesis and antimicrobial screening.
* Corresponding author. . Tel.: þ966 553753763; fax: þ966 14670560.
E-mail address: m_afroz007@yahoo.com (M.A. Bakht).
0223-5234/$ e see front matter Ó 2010 Elsevier Masson SAS. All rights reserved.
doi:10.1016/j.ejmech.2010.07.069

M.A. Bakht et al. / European Journal of Medicinal Chemistry 45 (2010) 5862e5869
5863
2. Molecular properties and drug-likeness
at Syracuse Research Corporation [24]. The XLOGP2 is an atom-
additive method applying corrections [25,26]. Computed partition
coefficients (XLOGP2 method) for drugs studied varied between
3.71e6.80 and by KoW-WIN method varied between 2.75 and 6.00
(Table 1). The LogKow (Kow-WIN) method is best supported for
most of the compounds on the basis of lipophilicity (ꢀ5) to
consider an oral drug/lead.
A molecular property is a complex balance of various structural
features which determine whether a particular molecule is similar
to the known drugs. It generally means “molecules which contain
functional groups and/or have physical properties consistent with
most of the known drugs”. These properties, mainly hydropho-
bicity, molecular size, flexibility and presence of various pharma-
cophoric features influence the behavior of molecules in a living
organism, including bioavailability. Computational chemists have
a wide array of tools and approaches available for the assessment of
molecular diversity. Diversity analysis has been shown to be an
important ingredient in designing drugs. So, computational sensi-
tivity analysis and structural analysis have been used to study the
drug-likeness of the candidate drug. As good bioavailability can be
achieved with an appropriate balance between solubility and par-
titioning properties. Thus in order to achieve good oral drugswe
have subjected a series of 1,3,4-oxadiazole derivatives (AB1eAB28)
for the prediction of lipophilicity, solubility and Lipinski “Rule of
Five” [14] and other properties for filtering compounds for subse-
quent synthesis and antimicrobial screening.
2.2. Solubility
An insufficient aqueous solubility is likely to impede bioavail-
ability of the drugs. Drug solubility is one of the important factors,
which affect the movement of a drug from the site of administra-
tion into the blood. It is well known that insufficient solubility of
drugs can lead to poor absorption [27]. Investigation of the rate-
limited steps of human oral absorption of 238 drugs [27] showed
that the absorption of a drug is usually very low if the calculated
solubility is <0.0001 mg/l. As per this criterion compounds of series
(AB1eAB28) almost fulfill the requirements of solubility (ALOGPS)
and could be considered as the candidate drugs (Table 1).
2.3. Absorption, polar surface area, and “Rule of five” properties
2.1. Lipophilicity
High oral bioavailability is an important factor for the develop-
ment of bioactive molecules as therapeutic agents. Good intestinal
absorption, reduced molecular flexibility (measured by the number
of rotatable bonds), low polar surface area or total hydrogen bond
count (sum of donors and acceptors), are important predictors of
good oral bioavailability [28,29]. Molecular properties such as
membrane permeability and bioavailability is always associated
with some basic molecular descriptors such as logP (partition coef-
ficient), molecular weight (MW), or hydrogen bond acceptors and
donors counts in a molecule [30]. Lipinski [14] used these molecular
properties in formulating his “Rule of Five”. The rule states that most
molecules with good membrane permeability have logP ꢀ5,
molecular weight ꢀ500, number of hydrogen bond acceptors ꢀ10,
and number of hydrogen bond donors ꢀ5. This rule is widely used as
a filter for drug-like properties. Table 2 contains calculated
percentage of absorption (%ABS), molecular polar surface area (PSA)
and Lipinski parameters of the investigated compounds of the series
(AB1eAB28). Magnitude of absorption is expressed by the
percentage of absorption. Absorption percent was calculated [25]
using the expression: %ABS ¼ 109 ꢁ 0.345 PSA. Polar surface area
(PSA) was determined by the fragment-based method of Ertl and
coworkers [31,32]. A poor permeation or absorption is more likely
when there are more than 5H bond donors, 10 H-bond acceptors.
Hydrogen-bonding capacity has been also identified as an important
parameter for describing drug permeability [29]. The series
(AB1eAB28) under investigation has most of the compounds pos-
sessing less number of hydrogen bond donors (ꢀ5) but do possess
considerable number of acceptors (ꢀ10) as shown in Table 2.
Number of rotatable bonds is important for conformational
changes of molecules under study and ultimately for the binding of
receptors or channels. It is revealed that for passing oral bioavail-
ability criteria, number of rotatable bond should be ꢀ10 [28]. The
compounds in this series (AB1eAB28) in general possess high
number of rotatable bonds (7e10) and therefore, exhibit large
conformational flexibility.
Poor solubility and poor permeability are amongst the main
causes for failure during drug development [15e17]. It is therefore,
important to determine these physico-chemical properties associ-
ated with a drug, before synthetic work is undertaken. The
computed logP values (P is the partition coefficient of the molecule
in the watereoctanol system) are shown in Table 1. The ALOGPS
method is part of the ALOGPS 2.1 program [18] used to predict
lipophilicity [19] and aqueous solubility [20,21] of compounds. The
lipophilicity calculations within this program are based on the
associative neural network approach and the efficient partition
algorithm. The LogKow (Kow-WIN) program [22,23] estimates the
log octanol/water partition coefficient (logP) of organic chemicals
and drugs using an atom/fragment contribution method developed
Table 1
Calculated partition coefficients and solubilities of the oxadiazoles investigated.
Compounds
ALOGPS
KoW-WIN
XLOGP2
AB1
AB2
AB3
AB4
AB5
AB6
AB7
AB8
ꢁ4.54 (11.87 mg/l)
ꢁ4.70 (8.83 mg/l)
ꢁ4.47 (16.74 mg/l)
ꢁ4.59 (11.89 mg/l)
ꢁ4.60 (10.61 mg/l)
ꢁ4.27 (22.82 mg/l)
ꢁ4.53 (12.99 mg/l)
ꢁ4.52 (13.49 mg/l)
ꢁ4.67 (10.15 mg/l)
ꢁ4.40 (20.99 mg/l)
ꢁ4.54 (14.14 mg/l)
ꢁ4.56 (12.61 mg/l)
ꢁ4.22 (27.65 mg/l)
ꢁ4.47 (16.03 mg/l)
ꢁ4.28 (22.45 mg/l)
ꢁ4.46 (15.97 mg/l)
ꢁ4.23 (30.12 mg/l)
ꢁ4.39 (19.44 mg/l)
ꢁ4.35 (19.63 mg/l)
ꢁ4.02 (42.58 mg/l)
ꢁ4.23 (27.11 mg/l)
ꢁ4.61 (11.16 mg/l)
ꢁ4.74 (8.95 mg/l)
ꢁ4.51 (16.61 mg/l)
ꢁ4.61 (12.44 mg/l)
ꢁ4.66 (10.26 mg/l)
ꢁ4.42 (18.12 mg/l)
ꢁ4.56 (13.43 mg/l)
6.00
4.46
4.60
3.53
4.26
3.23
3.74
3.80
4.44
4.69
3.61
4.34
3.32
3.82
3.23
3.88
4.12
3.05
3.78
2.75
3.26
3.53
4.18
4.42
3.35
4.08
3.05
3.56
3.71
6.62
6.80
5.89
6.44
5.59
5.68
5.91
6.54
6.71
5.81
6.35
5.51
5.60
5.59
6.22
6.39
5.49
6.03
5.19
5.28
5.89
6.51
6.69
5.78
6.33
5.49
5.57
AB9
AB10
AB11
AB12
AB13
AB14
AB15
AB16
AB17
AB18
AB19
AB20
AB21
AB22
AB23
AB24
AB25
AB26
AB27
AB28
Molecular polar surface area (PSA) is a very useful parameter for
the prediction of drug transport properties. PSA is a sum of surfaces
of polar atoms (usually oxygen, nitrogen and attached hydrogen) in
a molecule. PSA and volume is inversely proportional to %ABS.
Compound AB1, AB2, AB3 and AB5 have maximum absorption
(88.28%) as their corresponding polar surface area and volume are
least among the series (Table 2). Drug-likeness model score

5864
M.A. Bakht et al. / European Journal of Medicinal Chemistry 45 (2010) 5862e5869
Table 2
Calculated absorption (%ABS), polar surface area (PSA), Lipinski parameters and drug-likeness model score of the oxadiazoles investigated.
Compounds
%ABS
Volume (A3)
PSA (A2)
NROTB
HBA
HBD
log P, Calcd.
Formula weight
Drug-likeness model score
AB1
AB2
AB3
AB4
AB5
AB6
AB7
AB8
88.28
88.28
88.28
76.76
88.28
82.33
85.61
85.49
85.39
85.39
73.87
85.39
79.44
82.77
82.33
82.33
82.33
69.59
82.33
76.38
79.66
76.76
76.76
76.35
65.23
76.76
70.81
74.09
410.19
427.38
432.04
435.18
431.13
421.34
440.44
442.03
459.23
463.89
467.02
462.97
453.18
472.29
420.74
437.93
442.59
450.93
441.68
431.89
450.99
435.18
452.37
459.41
460.16
456.12
446.33
465.43
60.07
60.07
60.07
93.47
60.07
77.31
67.80
68.15
68.45
68.45
101.85
68.45
85.69
76.19
77.33
77.33
77.33
114.25
77.33
94.57
85.07
93.47
93.47
94.66
126.87
93.47
110.71
101.21
8
8
9
8
8
10
9
9
9
10
9
10
11
8
8
8
9
8
8
11
9
6
6
6
8
6
7
7
7
7
7
9
7
8
8
7
7
7
9
7
8
8
8
8
7
10
8
9
9
0
0
0
0
0
1
0
0
0
0
0
0
1
0
1
1
1
2
1
2
1
0
0
1
0
0
1
0
3.99
4.68
4.88
3.89
4.45
3.55
2.96
4.05
4.73
4.94
3.95
4.51
3.60
3.01
3.53
4.22
4.42
3.38
3.99
3.08
2.50
3.89
4.58
4.97
3.79
4.35
3.45
2.86
412
446
490
457
426
428
442
442
476
522
487
456
458
472
428
464
507
473
442
444
458
457
492
537
502
471
473
487
0.55
0.39
ꢁ0.02
ꢁ0.68
0.44
0.92
0.82
0.70
0.42
ꢁ0.09
ꢁ0.60
0.45
1.22
0.90
AB9
AB10
AB11
AB12
AB13
AB14
AB15
AB16
AB17
AB18
AB19
AB20
AB21
AB22
AB23
AB24
AB25
AB26
AB27
AB28
0.63
0.40
ꢁ0.09
0.20
0.44
1.06
0.83
ꢁ0.68
ꢁ0.71
ꢁ1.77
ꢁ0.87
ꢁ8.15
ꢁ0.30
ꢁ0.48
9
9
10
8
9
12
8
(a combined effect of physico-chemical properties, pharmacoki-
netics and pharmacodynamics of a compound and is represented
by a numerical value) was computed by MolSoft (MolSoft, 2007)
software for the 28 molecules under study. As shown in Fig. 1 the
green color indicates non drug-like behavior and those fall under
blue color are considered as drug-like. Computed drug-likeness
scores are presented in Table 2. Compounds having zero or negative
value should not be considered as drug-like. Maximum drug-like-
ness score was found out to be 1.22 for compound AB13.
values 8.3e15.7 Hz. Similarly a singlet appeared at
to the protons of the methoxy group and the OCH2 protons reso-
nated as a singlet between 4.8e4.2. The mass spectrum of
compounds are characterized by molecular ion peak at m/z (Mþ1or
ꢁ1), which is in agreement with their respective molecular
d 3.7e3.6 owing
d
M
After successful prediction of molecular properties of the series
(AB1eAB28) under investigation, 16 compounds were selected out
of 28 for the next steps of synthesis and antimicrobial screening. On
the basis of drug-likeness model score compounds (AB3, AB4,
AB10, AB11, AB17 and AB22eAB28) failed to be treated like
candidate drugs. So it was observed that those compounds (AB3,
AB4, AB10, AB11, AB17) having nitro/bromo substituted phenyl
group at 5th position of 1,3,4-oxadiazole moiety and compounds
(AB22eAB28) having nitro substituted phenyl group at 2nd posi-
tion of oxadiazole moiety failed to comply with the parameters of
Lipinski-Rule of five (Ro5) and their drug-likeness model score was
also not adequate to be treated like candidate drugs.
3. Results and discussion
3.1. Chemistry
The compounds (IIIeV) in 1H NMR spectrum exhibited two
doublets with J values between 13.0 and 12.6 Hz conforming the
trans coupling.
Formation of 1,3,4-oxadiazoles {(AB1eAB2), (AB5eAB9),
(AB12eAB16), (AB18eAB21)} was confirmed by recording their IR,
1H NMR and mass spectra. In general IR spectrum of compounds
showed absorption at 1561e1549 cmꢁ1 due to the C]N group,
band at 1171e1155 cmꢁ1 due to stretching of oxadiazole ring.
The 1H NMR spectrum of compounds in general showed
multiplet in the region of
d 8.7e6.8 due to aromatic proton. At
Fig. 1. Graph showing compound (AB13) of maximum drug-likeness model score
d
7.2e6.1 appeared as two doublets due to alkenyl proton with J
using MolSoft 2007.

M.A. Bakht et al. / European Journal of Medicinal Chemistry 45 (2010) 5862e5869
5865
formulas. The spectral values for all the compounds and C, H, N
analysis are given in the Experimental part.
results obtained from antimicrobial screening it was found that
compound AB13, (E)-3-(4-((5-(2-hydroxyphenyl)-1,3,4-oxadiazol-2-yl)
methoxy)-3-methoxyphenyl)-1-(4-methoxy phenyl)prop-2-en-1-
one and AB20, (E)-3-(4-((5-(2-hydroxyphenyl)-1,3,4-oxadiazol-2-yl)
methoxy)-3-methoxyphenyl)-1-(4-hydroxyphenyl)prop-2-en-1-one
were most active of the series. Examining closely on substitu-
tions, it may be concluded that role of electron donating groups
(eOH) on the phenyl ring of 1,3,4-oxadiazole has great influence
on antimicrobial activity. This result is further supported by the
fact that their molecular property and drug-likeness model score
were maximum among the series. Finally it is conceivable that
further derivatization of such compounds will be of great interest
with the hope to get more selective antimicrobial agents.
3.2. Pharmacology
3.2.1. Antibacterial activity
The investigation of antibacterial screening data revealed that
all the tested compounds showed moderate to good bacterial
inhibition. Compounds AB6, AB13, AB14, AB15 and AB20 showed
good bacterial inhibition. Most of them exhibited good antibacterial
activity largely against Escherichia coli and Pseudomonas aeruginosa.
Compound AB13 showed almost equivalent antibacterial activity to
standard Ciprofloxacin. MBC of compound AB13 was found to be
same as MIC, against Staphylococcus aureus, but in most of the
compounds MBC was two, three or four folds higher than their
corresponding MIC values. Compound AB13 showed good anti-
bacterial activity against almost all bacterial strains.
5. Chemistry
The synthesis of 1,3,4-oxadiazole derivatives {(AB1eAB2),
(AB5eAB9), (AB12eAB16), (AB18eAB21)}, described in this study
are outlined in Scheme 1 and physical data is presented in Table 3.
The chalcones (IIIeV) were prepared by reacting 2-(4-formyl-2-
methoxyphenoxy) acetic acid (I) and appropriate acetophenone (II)
in the presence of a base by conventional ClaiseneSchmidt
condensation. Reaction between newly synthesized chalcones with
appropriate acid hydrazide in 5 ml of phosphorus oxychloride
(POCl3) gave 1,3,4-oxadiazoles in good yield. The compounds were
recrystallized from ethanol. The purity of the compounds was
checked by TLC. Spectral data 1H NMR, IR of all the synthesized
compounds and Mass spectra of selected compounds were recor-
ded and found in full agreement with the proposed structures. The
elemental analysis results were within ꢂ0.4% of the theoretical
values.
3.2.2. Antifungal activity
Antifungal screening data indicates that most of the compounds
showed moderate activity. Among the screened compounds, AB13
and AB20 showed good inhibition against both of selected fungal
strains i.e. Aspergillus niger and Candida albicans. MFC of most of the
compounds was found to be two to four folds higher than their
corresponding MIC results.
4. Conclusion
A series (AB1eAB28) of 1,3,4-oxadiazoles were subjected for the
prediction of molecular properties and drug-likeness by different
softwares in order to find suitable molecules for the synthesis and
antimicrobial screening. Among the series only 16 compounds
{(AB1eAB2), (AB5eAB9), (AB12eAB16), (AB18eAB21)} were chosen
on the basis of molecular properties and drug-likeness score for oral
bioavailability. Selected compounds {(AB1eAB2), (AB5eAB9),
(AB12eAB16), (AB18eAB21)} were subjected for the synthesis and
antimicrobial screening. The synthesis of 1,3,4-oxadiazole derivatives
{(AB1eAB2), (AB5eAB9), (AB12eAB16), (AB18eAB21)} was governed
by reacting newly formed chalcones (IIIeV) which were previously
prepared by reacting 2-(4-formyl-2-methoxyphenoxy) acetic acid (I)
and acetophenones (II). Condensation of newly formed chalcones
(IIIeV) with different acid hydrazides yielded respective oxadiazole
derivatives {(AB1eAB2), (AB5eAB9), (AB12eAB16), (AB18eAB21)}.
All the synthesized compounds were screened for antibacterial and
antifungal activity by adopting standard protocol. On the basis of
6. Pharmacology
6.1. Antibacterial studies
The newly prepared compounds were screened for their anti-
bacterial activity against E. coli (ATCC-25922), S. aureus (ATCC-
25923), P. aeruginosa (ATCC-27853) and Bacillus subtilis (ATCC-
6633) (recultured) bacterial strains by disc-diffusion method
[33,34]. A standard inoculum (1e2 ꢃ 107 c.f.u./ml 0.5 McFarland
standards) was introduced on to the surface of sterile agar plates,
and a sterile glass spreader was used for even distribution of the
inoculum. The discs measuring 6.25 mm in diameter were prepared
from Whatman no. 1 filter paper and sterilized by dry heat at 140 ꢄC
HX
O
H
C
KOH / CH3OH
3
HO
O
O
CHO
R
+
HB
O
R
O
O
(III-V)
HO
O
I
R = H, OCH3, OH
CH3
II
CH3
O
R'CONHNH2
POCl3
HX
O
HB
N
O
R
N
O
O
CH3
R'
(AB1-AB2), (AB5-AB9), (AB12-AB16), (AB18-AB21)
Scheme 1. Schematic representation for synthesis of 1,3,4-oxadiazoles.

5866
M.A. Bakht et al. / European Journal of Medicinal Chemistry 45 (2010) 5862e5869
Table 3
and spectrophotometrically. The lowest concentration (highest
dilution) required to arrest the growth of bacteria was regarded as
minimum inhibitory concentration (MIC).
To obtain the minimum bacterial concentration (MBC), 0.1 ml
volume was taken from each tube and spread on agar plates. The
number of c.f.u. was counted after 18e24 h of incubation at 35 ꢄC.
MBC was defined as the lowest drug concentration at which 99.9%
of the inoculum was killed. The minimum inhibitory concentration
and minimum bactericidal concentration are given in Table 5.
Physical constants of the synthesized compounds.
Compound No.
R
R0
Yield (%)
Molecular
Weight
Melting
point (ꢄC)
AB1
AB2
AB5
AB6
AB7
AB8
AB9
AB12
AB13
AB14
AB15
AB16
AB18
AB19
AB20
AB21
H
H
H
H
C6H5
91
84
79
73
76
68
72
78
83
77
82
71
89
69
71
78
412
446
426
428
442
442
476
456
458
472
428
463
473
442
444
458
175e177
168e170
170e172
175e177
176e178
164e166
146e148
161e163
129e131
103e105
162e164
157e159
160e162
167e169
120e122
130e132
p-CleC6H4
p-CH3eC6H4
o-OHeC6H4
C6H5eOCH2
C6H5
p-CleC6H4
p-CH3eC6H4
o-OHeC6H4
C6H5eOCH2
C6H5
p-CleC6H4
p-NO2eC6H4
p-CH3eC6H4
o-OHeC6H4
C6H5eOCH2
H
OCH3
OCH3
OCH3
OCH3
OCH3
OH
OH
OH
OH
OH
OH
6.2. Antifungal studies
The newly prepared compounds were screened for their anti-
fungal activity against C. albicans and A. niger in DMSO by agar
diffusion method [35,36]. Sabourauds agar media was prepared by
dissolving peptone (1 g), D-glucose (4 g) and agar (2 g) in distilled
water (100 ml) and adjusting pH to 5.7. Normal saline was used to
make a suspension of spore of fungal strain for lawning. A loopful of
particular fungal strain was transferred to 3 ml saline to get
a suspension of corresponding species. Twenty milliliters of agar
media was poured into each Petri dish. Excess of suspension was
decanted and the plates were dried by placing in an incubator at
37 ꢄC for 1 h. Using an agar punch, wells were made and each well
was labeled. A control was also prepared in triplicate and main-
tained at 37 ꢄC for 3e4 days. The fungal activity of each compound
was compared with voriconazole as a standard drug. Inhibition
zones were measured and compared with the controls. The fungal
zones of inhibition values are given in Table 6.
The nutrient broth, which contained logarithmic serially two
fold diluted amount of test compound and controls was inoculated
with approximately 1.6 ꢃ 104e6 ꢃ 104 c.f.u./ml. The cultures were
incubated for 48 h at 35 ꢄC and the growth was monitored. The
lowest concentration (highest dilution) required to arrest the
growth of fungus was regarded as minimum inhibitory concen-
tration (MIC). To obtain the minimum fungicidal concentration
(MFC), 0.1 ml volume was taken from each tube and spread on agar
plates. The number of c.f.u. was counted after 48 h of incubation at
35 ꢄC. MFC was defined as the lowest drug concentration at which
99.9% of the inoculums were killed. The minimum inhibitory
concentration and minimum fungicidal concentration are given in
Table 7.
for 1 h. The sterile discs previously soaked with the test compound
solution in DMSO of specific concentration 100 g and 200 g/disc
m
m
were carefully placed on the agar culture plates. The plates were
inverted and incubated for 24 h at 37 ꢄC. Ciprofloxacin was used as
a standard drug. Inhibition zones were measured and compared
with the controls. The bacterial zones of inhibition values are given
in Table 4. Minimum inhibitory concentrations (MICs) were deter-
mined 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 ꢃ 105 c.f.u. of actively dividing bacteria cells. The cultures were
incubated for 24 h at 37 ꢄC and the growth was monitored visually
Table 4
Antibacterial zone of inhibition (mm) of oxadiazoles.
Compounds
Conc. (
m
g/ml) Zone of inhibition (mm)
S. aureus B. subtilis E. coli P. aeruginosa
AB1
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
16
18
12
14
15
16
17
19
15
17
16
18
14
15
15
17
21
23
17
19
17
18
13
15
12
13
15
17
19
20
17
18
23
24
13
14
9
19
20
16
18
19
21
20
22
18
20
19
21
17
19
19
21
25
26
21
22
21
23
16
18
15
17
19
20
23
24
20
22
26
27
23
25
19
22
23
25
25
27
23
24
25
26
22
24
23
24
30
32
26
28
25
27
22
23
21
23
23
25
27
28
25
27
32
33
AB2
11
12
14
15
16
12
14
12
14
12
13
12
14
18
20
13
16
13
15
11
13
10
11
12
14
16
18
14
16
21
22
AB5
AB6
Table 5
AB7
MIC and MBC results of oxadiazoles.
AB8
Comp.
S. aureus
B. subtilis
E. coli
P. aeruginosa
MIC
MBC
MIC
MBC
MIC
MBC
MIC
MBC
AB9
AB1
AB2
AB5
AB6
AB7
AB8
AB9
AB12
AB13
AB14
AB15
AB16
AB18
AB19
AB20
AB21
Std
12.5
12.5
6
6
6
12.5
12.5
12.5
6
12.5
25
25
25
25
6
50
25
25
12.5
12.5
25
50
25
6
25
25
6
6
6
50
12.5
12.5
6
25
25
25
12.5
12.5
25
100
25
12.5
12.5
50
50
100
25
25
25
12.5
6
12.5
12.5
12.5
12.5
12.5
25
25
25
12.5
25
6
50
50
50
12.5
25
50
100
25
25
12.5
50
100
100
100
12.5
25
AB12
AB13
AB14
AB15
AB16
AB18
AB19
AB20
AB21
12.5
12.5
12.5
25
12.5
50
6
12.5
6
12.5
12.5
6
12.5
12.5
12.5
12.5
12.5
6
12.5
12.5
12.5
6
6
25
12.5
25
50
12.5
12.5
6
25
12.5
12.5
25
25
50
25
12.5
25
50
100
50
50
12.5
12.5
12.5
25
12.5
12.5
6
6
12.5
6
12.5
6
12.5
6
12.5
MIC (
m
g/ml) ¼ minimum inhibitory concentration, i.e., the lowest concentration to
g/ml) minimum bactericidal
completely inhibit bacterial growth; MBC
concentration, i.e., the lowest concentration to completely kill bacteria. Cipro-
(
m
¼
Std. (Ciprofloxacin) 100
200
floxacin is used as standard drug.

M.A. Bakht et al. / European Journal of Medicinal Chemistry 45 (2010) 5862e5869
5867
Table 6
uncorrected. Thin layer chromatography (TLC) plates (silica gel G),
were used to confirm the purity of the commercial reagents used,
compounds synthesized and to monitor the reactions as well. Two
different solvent systems, toluene: ethyl acetate: formic acid
(5:4:1) and petroleum ether: toluene: acetic acid (5:4:1), were used
to run the TLC. The spots were located under iodine vapors/UV
light. IR spectra were obtained on a PerkineElmer 1720 FT-IR
spectrometer (KBr Pellets). 1H NMR spectra were recorded on
a Bruker AC 400 MHz, spectrometer-using TMS as internal standard
in DMSO-d6. The FAB mass spectra were recorded on a JEOLSX 102/
DA-6000 Mass Spectrometer.
Antifungal zone of inhibition (mm) of oxadiazoles.
Compounds
Conc. (
m
g/ml)
Zone of inhibition (mm)
Aspergillus niger
Candida albicans
AB1
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
21
25
18
20
20
22
22
25
22
25
23
24
19
21
20
23
25
26
16
19
22
24
18
21
17
19
20
23
27
29
22
24
28
30
16
18
12
15
15
16
18
20
16
18
15
17
16
17
16
18
19
21
11
14
16
18
14
17
13
15
15
17
21
24
17
19
24
26
AB2
AB5
AB6
AB7
7.1.1. General procedure for the synthesis of chalcones (IIIeV)
A mixture of 2-(4-formyl-2-methoxyphenoxy) acetic acid (I)
(0.01 mol) and appropriate acetophenone (II) (0.01 mol) is reacted
as per ClaiseneSchmidt condensation, in absolute methanol were
stirred at room temperature in the presence of base (alcoholic
solution of potassium hydroxide 30%; 5 mL) till completion of the
reaction. The reaction mixture was allowed to stand overnight and
then poured into ice-cold water followed by neutralization with
HCl. The solid separated was filtered, dried and crystallized from
ethanol. The purity of the chalcone was checked by TLC.
AB8
AB9
AB12
AB13
AB14
AB15
AB16
AB18
AB19
AB20
AB21
Std. (Voriconazole)
7.1.1.1. 2-(2-Methoxy-4-((E)-3-oxo-3-phenylprop-1-enyl)phenoxy)
acetic acid (III). IR: (KBr) cmꢁ1: 3174 (COOH), 1706e1692 (2C]O),
1560 (C]C). 1H NMR (DMSO-d6) ppm: 10.1 (1H, s, COOH); 8.3e7.2
(8H, m, Ar-H); 6.8 (1H, d, HB, J ¼ 12.6 Hz); 6.6 (1H, d, Hx,
J ¼ 12.9 Hz); 4.5 (2H, s, OCH2); 3.7(3H, s, OCH3); m/z: 313 (Mþ1).
7.1.1.2. 2-(2-Methoxy-4-((E)-3-(4-methoxyphenyl)-3-oxoprop-1-enyl)
phenoxy)acetic acid (IV). IR: (KBr) cmꢁ1: 3188 (COOH), 1706e1695
(2C]O), 1540 (C]C). 1H NMR (DMSO-d6) ppm: 10.5 (1H, s, COOH);
8.3e7.2 (7H, m, Ar-H); 7.1 (1H, d, HB, J ¼ 12.7 Hz); 7.0 (1H, d, Hx,
J ¼ 12.7 Hz); 4.5 (2H, s, OCH2); 3.8 (6H, s, 2 ꢃ OCH3); m/z: 341(Mꢁ1).
7. Experimental
7.1.1.3. 2-(4-((E)-3-(4-hydroxyphenyl)-3-oxoprop-1-enyl)-2-methoxy-
phenoxy) acetic acid (V). IR: (KBr) cmꢁ1: 3550 (OH), 3092 (COOH),
1706e1692 (2C]O) 1539 (C]C). 1H NMR (DMSO-d6) ppm: 9.8 (1H,
s, COOH); 9.1(1H, s, OH); 7.8e7.2 (7H, m, Ar-H); 7.0 (1H, d, HB,
J ¼ 13 Hz); 6.9 (1H, d, Hx, J ¼ 13 Hz); 4.5 (2H, s, OCH2); 3.8 (3H, s,
OCH3); m/z: 329 (Mþ1).
7.1. Chemistry
All the chemicals used were laboratory grade and procured from
E. Merck (Germany) and S.D. Fine Chemicals (India). Melting points
were determined by open tube capillary method and are
7.1.2. General procedure for synthesis of 1,3,4-oxadiazole derivatives
(AB1eAB2), (AB5eAB9), (AB12eAB16), (AB18eAB21)
Table 7
To an equimolar mixture (0.001 mol) of chalcone derivative (III,
IV, V) and appropriate acid hydrazide in 5 ml of phosphorus oxy-
chloride (POCl3) was added and the reaction mixture was refluxed
for 18e20 h. After completion of reaction the mixture was poured
onto crushed ice (20 g) and neutralized with aqueous sodium
hydroxide solution. The product so obtained was filtered, washed
with water and recrystallized from ethanol.
MIC and MFC Results of oxadiazoles.
Comp.
A. niger
C.albicans
MIC
MFC
MIC
MFC
AB1
AB2
AB5
12.5
12.5
e
25
25
12.5
25
12.5
6
12.5
6
25
50
25
12.5
25
e
AB6
6
12.5
12.5
25
50
25
12.5
12.5
50
AB7
6
7.1.2.1. (E)-3-(4-((5-phenyl-1,3,4-oxadiazol-2-yl)methoxy)-3-methoxy-
phenyl)-1-phenylprop-2-en-1-one (AB1). IR: (KBr) cmꢁ1: 1682 (C]
O), 1654 (C]C), 1560 (C]N), 1167 (CeOeC). 1H NMR (DMSO-d6)
ppm: 7.8e7.2 (13H, m, Ar-H); 6.8e6.6 (Alkenyl proton, 2H, 2d,
J ¼ 12.6, 12.9 Hz); 4.5 (2H, s, OCH2); 3.7 (3H, s, OCH3); m/z: 413
(Mþ1); Anal. Calcd. for C25H20N2O4: C, 72.80; H, 4.89; N, 6.79%.
Found: C, 72.82; H, 4.90; N, 6.80%.
AB8
AB9
12.5
12.5
12.5
6
6
25
e
25
e
e
AB12
AB13
AB14
AB15
AB16
AB18
AB19
AB 20
AB21
Std (Voriconazole)
12.5
6
12.5
12.5
12.5
e
25
12.5
25
25
25
e
25
25
6
6
6
100
50
12.5
12.5
12.5
e
25
6
12.5
6
100
12.5
25
7.1.2.2. (E)-3-(4-((5-(4-chlorophenyl)-1,3,4-oxadiazol-2-yl)methoxy)-
3-methoxyphenyl)-1-phenylprop-2-en-1-one (AB2). IR: (KBr) cmꢁ1
:
12.5
1682 (C]O),1654 (C]C), 1560 (C]N), 1166 (CeOeC). 1H NMR
(DMSO-d6) ppm: 8.3e7.0 (12H, m, Ar-H); 6.8e6.5 (Alkenyl proton,
2H, 2d, J ¼ 8.8, 10.9 Hz); 4.5 (2H, s, CH2); 3.8 (3H, s, OCH3); m/z: 448
MIC (
completely inhibit fungal growth; MFC (
tion, i.e., the lowest concentration to completely kill the fungi.
m
g/ml) ¼ minimum inhibitory concentration, i.e., the lowest concentration to
m
g/ml) ¼ minimum fungicidal concentra-

5868
M.A. Bakht et al. / European Journal of Medicinal Chemistry 45 (2010) 5862e5869
(Mþ1); Anal. Calcd. for C25H19ClN2O4: C, 67.19; H, 4.29; N, 6.27%.
Found: C, 67.18; H, 4.30; N, 6.29%.
proton, 2H, 2d, J ¼ 8.3, 8.4 Hz); 4.8e4.6 (4H, s, 2 ꢃ OCH2); 3.7e3.6
(6H, s, 2 ꢃ OCH3); m/z: 473 (Mþ1); Anal. Calcd. for C27H24N2O6: C,
68.63; H, 5.12; N, 5.93%. Found: C, 68.6; H, 5.13; N, 5.94%.
7.1.2.3. (E)-3-(4-((5-p-tolyl-1,3,4-oxadiazol-2-yl)methoxy)-3-methoxy-
phenyl)-1-phenylprop-2-en-1-one (AB5). IR: (KBr) cmꢁ1: 1680 (C]
O), 1654 (C]C), 1560 (C]N), 1167 (CeOeC). 1H NMR (DMSO-d6)
ppm: 8.2e7.1 (12H, m, Ar-H); 6.8e6.6 (Alkenyl proton, 2H, 2d,
J ¼ 12.2, 15.7 Hz); 4.5 (2H, s, OCH2); 3.8 (3H, s, OCH3); 2.2 (3H, s,
CH3); m/z: 427 (Mþ1); Anal. Calcd. for C26H22N2O4: C, 73.22; H, 5.20;
N, 6.57%. Found: C, 73.25; H, 5.21; N, 6.59%.
7.1.2.11. (E)-3-(4-((5-phenyl-1,3,4-oxadiazol-2-yl)methoxy)-3-methoxy-
phenyl)-1-(4-hydroxyphenyl)prop-2-en-1-one (AB15). IR: (KBr) cmꢁ1
:
3550 (OH), 1680 (C]O), 1654 (C]C), 1559 (C]N), 1156 (CeOeC).
1H NMR (DMSO-d6) ppm: 9.2 (1H, s, OH); 8.5e7.3 (12H, m, Ar-H);
7.2e6.7 (Alkenyl proton, 2H, 2d, J ¼ 12.3, 15.0 Hz); 4.4 (2H, s, OCH2);
3.8 (3H, s, OCH3); m/z: 429 (Mþ1); Anal. Calcd. for C25H20N2O5: C,
70.08; H, 4.71; N, 6.54%. Found: C, 70.05; H, 4.73; N, 6.54%.
7.1.2.4. (E)-3-(4-((5-(2-hydroxyphenyl)-1,3,4-oxadiazol-2-yl)methoxy)-
3-methoxyphenyl)-1-phenylprop-2-en-1-one (AB6). IR: (KBr) cmꢁ1
:
7.1.2.12. (E)-3-(4-((5-(4-chlorophenyl)-1,3,4-oxadiazol-2-yl)methoxy)-
3-methoxy phenyl)-1-(4-hydroxyphenyl)prop-2-en-1-one (AB16). IR:
(KBr) cmꢁ1: 3550 (OH), 1682 (C]O), 1654 (C]C), 1560 (C]N), 1155
(CeOeC). 1H NMR (DMSO-d6) ppm: 9.2 (1H, s, OH); 8.2e7.7 (11H,
m, Ar-H); 6.8e6.7 (Alkenyl proton, 2H, 2d, J ¼ 14.7,15.6 Hz); 4.5 (2H,
s, OCH2); 3.8 (3H, s, OCH3); m/z: 464 (Mþ1); Anal. Calcd. for
C25H19ClN2O5: C, 64.87; H, 4.14; N, 6.05%. Found: C, 64.85; H, 4.13;
N, 6.07%.
3536 (OH), 1682 (C]O), 1654 (C]C), 1556 (C]N), 1166 (CeOeC). 1H
NMR (DMSO-d6) ppm: 9.1 (1H, s, OH); 8.3e7.1 (12H, m, Ar-H); 6.7e6.5
(Alkenyl proton, 2H, 2d, J ¼ 12.4, 12.6 Hz); 4.6 (2H, s, OCH2); 3.7 (3H, s,
OCH3); m/z: 429 (Mþ1); Anal. Calcd. for C25H20N2O5: C, 70.08; H, 4.71;
N, 6.54%. Found: C, 70.09; H, 4.71; N, 6.56%.
7.1.2.5. (E)-3-(4-((5-(phenoxymethyl)-1,3,4-oxadiazol-2-yl)methoxy)
-3-methoxyphenyl)-1-phenylprop-2-en-1-one
(AB7). IR:
(KBr)
cmꢁ1: 1686 (C]O), 1654 (C]C), 1560 (C]N), 1171 (CeOeC). 1H
NMR (DMSO-d6) ppm: 8.2e6.8 (13H, m, Ar-H); 6.6e6.2 (Alkenyl
proton, 2H, 2d, J ¼ 10.6, 10.7 Hz); 4.7e4.5(4H, s, 2 ꢃ OCH2); 3.8 (3H,
s, OCH3); m/z: 443(Mþ1); Anal. Calcd. for C26H22N2O5: C, 70.58; H,
5.01; N, 6.33%. Found: C, 70.59; H, 5.03; N, 6.36%.
7.1.2.13. (E)-3-(4-((5-(4-nitrophenyl)-1,3,4-oxadiazol-2-yl)methoxy)-
3-methoxy phenyl)-1-(4-hydroxyphenyl)prop-2-en-1-one (AB18). IR:
(KBr) cmꢁ1: 3550 (OH), 1686 (C]O), 1654 (C]C), 1560 (C]N), 1158
(CeOeC). 1H NMR (DMSO-d6) ppm: 9.2 (1H, s, OH); 8.3e7.0 (11H, m,
Ar-H); 6.7e6.5 (Alkenyl proton, 2H, 2d, J ¼ 12.8, 13.2 Hz); 4.4 (2H, s,
OCH2); 3.6 (3H, s, OCH3); m/z: 474 (Mþ1); Anal. Calcd. for C25H19N3O7:
C, 63.42; H, 4.05; N, 8.88%. Found: C, 63.43; H, 4.07; N, 8.91%.
7.1.2.6. (E)-3-(4-((5-phenyl-1,3,4-oxadiazol-2-yl)methoxy)-3-methoxy-
phenyl)-1-(4-methoxyphenyl)prop-2-en-1-one (AB8). IR: (KBr) cmꢁ1
:
1682 (C]O), 1654 (C]C), 1561 (C]N), 1157 (CeOeC). 1H NMR
(DMSO-d6) ppm: 8.0e7.2 (12H, m, Ar-H); 7.1e6.9 (Alkenyl proton,
2H, 2d, J ¼ 10.1,10.8 Hz); 4.5 (2H, s, OCH2); 3.9e3.8 (6H, s, 2ꢃOCH3);
m/z: 443(Mþ1); Anal. Calcd. for C26H22N2O5: C, 70.58; H, 5.01; N,
6.33%. Found: C, 70.59; H, 5.03; N, 6.36%.
7.1.2.14. (E)-3-(4-((5-p-tolyl-1,3,4-oxadiazol-2-yl)methoxy)-3-methoxy-
phenyl)-1-(4-hydroxyphenyl)prop-2-en-1-one (AB19). IR: (KBr) cmꢁ1
:
3550 (OH), 1682 (C]O), 1654 (C]C), 1559 (C]N), 1156 (CeOeC). 1H
NMR (DMSO-d6) ppm: 8.5 (1H, s, OH); 8.3e7.1 (11H, m, Ar-H); 7.0e6.8
(Alkenyl proton, 2H, 2d, J ¼ 12.4,12.3 Hz); 4.4 (2H, s, OCH2); 3.8 (3H, s,
OCH3);2.3(3H, s,CH3);m/z:443(Mþ1);Anal.Calcd.forC26H22N2O5:C,
70.58; H, 5.01; N, 6.33%. Found: C, 70.57; H, 5.03; N, 6.36%.
7.1.2.7. (E)-3-(4-((5-(4-chlorophenyl)-1,3,4-oxadiazol-2-yl)methoxy)-
3-methoxyphenyl)-1-(4-methoxyphenyl)prop-2-en-1-one (AB9). IR:
(KBr) cmꢁ1: 1682 (C]O), 1654 (C]C), 1559 (C]N), 1158 (CeOeC).
1H NMR (DMSO-d6) ppm: 8.2e7.1 (11H, m, Ar-H); 6.7e6.6 (Alkenyl
proton, 2H, 2d, J ¼ 10.1, 10.8 Hz); 4.5 (2H, s, OCH2); 3.8e3.7 (6H, s,
2 ꢃ OCH3); m/z: 478 (Mþ1); Anal. Calcd. for C26H21ClN2O5: C, 65.48;
H, 4.44; N, 5.87%. Found: C, 65.49; H, 4.48; N, 5.86%.
7.1.2.15. (E)-3-(4-((5-(2-hydroxyphenyl)-1,3,4-oxadiazol-2-yl)methoxy)-
3-methoxy phenyl)-1-(4-hydroxyphenyl)prop-2-en-1-one (AB20). IR:
(KBr) cmꢁ1: 3550e3536 (2OH), 1680 (C]O), 1654 (C]C), 1549 (C]
N), 1155 (CeOeC). 1H NMR (DMSO-d6) ppm: 10.8 (2H, s, 2 ꢃ OH);
8.0e6.9 (11H, m, Ar-H); 6.7e6.1 (Alkenyl proton, 2H, 2d, J ¼ 10.4,
9.6 Hz); 4.4 (2H, s, OCH2); 3.7 (3H, s, OCH3); m/z: 445 (Mþ1); Anal.
Calcd. for C25H20N2O6: C, 67.56; H, 4.54; N, 6.30%. Found: C, 67.57;
H, 4.57; N, 6.33%.
7.1.2.8. (E)-3-(4-((5-p-tolyl-1,3,4-oxadiazol-2-yl)methoxy)-3-methoxy-
phenyl)-1-(4-methoxyphenyl)prop-2-en-1-one (AB12). IR: (KBr) cmꢁ1
:
1682 (C]O), 1654 (C]C), 1560 (C]N), 1158 (CeOeC). 1H NMR
(DMSO-d6) ppm: 8.0e7.2 (11H, m, Ar-H); 6.7e6.3 (Alkenyl proton,
2H, 2d, J ¼ 12.1, 12.2 Hz); 4.4 (2H, s, OCH2); 3.7e3.6 (6H, s,
2 ꢃ OCH3); 2.3 (3H, s, CH3); m/z: 457(Mþ1); Anal. Calcd. for
C27H24N2O5: C, 71.04; H, 5.30; N, 6.14%. Found: C, 71.03; H, 5.33; N,
6.16%.
7.1.2.16. (E)-3-(4-((5-(phenoxymethyl)-1,3,4-oxadiazol-2-yl)methoxy)-
3-methoxy phenyl)-1-(4-hydroxyphenyl)prop-2-en-1-one (AB21). IR:
(KBr) cmꢁ1: 3550 (OH), 1682 (C]O), 1654 (C]C), 1559 (C]N), 1156
(CeOeC). 1H NMR (DMSO-d6) ppm: 9.4 (1H, s, OH); 8.7e7.0 (12H,
m, Ar-H); 6.9e6.5 (Alkenyl proton, 2H, 2d, J ¼ 12.5, 13.4 Hz);
4.4e4.2 (4H, s, 2 ꢃ OCH2); 3.8 (3H, s, OCH3); m/z: 459 (Mþ1); Anal.
Calcd. for C26H22N2O6: C, 68.11; H, 4.84; N, 6.11%. Found: C, 68.13; H,
4.87; N, 6.13%.
7.1.2.9. (E)-3-(4-((5-(2-hydroxyphenyl)-1,3,4-oxadiazol-2-yl)methoxy)-
3-methoxyphenyl)-1-(4-methoxyphenyl)prop-2-en-1-one (AB13). IR:
(KBr) cmꢁ1: 3535 (OH), 1682 (C]O), 1654 (C]C), 1561 (C]N), 1158
(CeOeC). 1H NMR (DMSO-d6) ppm: 9.2 (1H, s, OH); 8.1e7.2 (11H, m,
Ar-H); 6.8e6.5 (Alkenyl proton, 2H, 2d, J ¼ 10.3, 10.7 Hz); 4.7 (2H, s,
OCH2); 3.7e3.6 (6H, s, 2 ꢃ OCH3); m/z: 459(Mþ1); Anal. Calcd. for
C26H22N2O6: C, 68.11; H, 4.84; N, 6.11%. Found: C, 68.13; H, 4.83; N,
6.14%.
Acknowledgments
The authors wish to express the gratitude to the staff of Jamia
Hamdard for providing necessary facility to carry out the research
work.
7.1.2.10. (E)-3-(4-((5-(phenoxymethyl)-1,3,4-oxadiazol-2-yl)methoxy)-
3-methoxyphenyl)-1-(4-methoxyphenyl)prop-2-en-1-one (AB14). IR:
(KBr) cmꢁ1: 1682 (C]O), 1654 (C]C), 1560 (C]N), 1157 (CeOeC).
1H NMR (DMSO-d6) ppm: 7.9e6.9 (12H, m, Ar-H); 6.9e6.8 (Alkenyl
References
[1] S.J. Dolman, F. Gosselin, P.D. O’Shea, I.W. Davies, J. Org. Chem. 71 (2006)
9548e9551.

M.A. Bakht et al. / European Journal of Medicinal Chemistry 45 (2010) 5862e5869
5869
[2] M.D. Mullican, M.W. Wilson, D.T. Connor, C.R. Kostlan, D.J. Schrier, R.D. Dyer, J.
Med. Chem. 361 (1993) 1090e1099.
[19] I.V. Tetko, V.Y. Tanchuk, A.E.P. Villa, J. Chem. Inf. Comput. Sci. 41 (2001)
1407e1421.
[3] D.H. Boschelli, D.T. Connor, D.A. Bornemeier, R.D. Dyer, J.A. Kennedy,
P.J. Kuipers, G.C. Okonkwo, D.J. Schrier, C.D. Wright, J. Med. Chem. 36 (1993)
1802e1810.
[4] K. Raman, K.H. Singh, S.K. Salzman, S.S. Parmar, J. Pharm. Sci. 821 (1993)
167e169.
[20] I.V. Tetko, V.Y. Tanchuk, T.N. Kasheva, A.E.P. Villa, J. Chem. Inf. Comput. Sci. 41
(2001) 1488e1493.
[21] K.V. Balakin, N.P. Savchuk, I.V. Tetko, Curr. Med. Chem. 13 (2006) 223e241.
[22] W.M. Meylan, P.H. Howard, J. Pharm. Sci. 84 (1995) 83e92.
[23] M. Remko, J. Mol. Struc: Theochem 897 (2009) 73e82.
[24] http://www.srcinc.com/what-we-do/databaseforms.aspx?id¼385/10/06/
2008.
[5] G. Sahin, E. Palaska, P. Kelicen, R. Demirdamar, G. Altinok, F. Arzneim, Drug
Res. 51 (2001) 478e484.
[6] S.L. Gaonkar, K.M.L. Rai, B. Prabhuswamy, Eur. J. Med. Chem. 41 (2006)
841e846.
[7] A.A. El-Emam, O.A. Al-Deeb, M. Al-Omar, J. Lehmann, Bioorg. Med. Chem. 12
(2004) 5107e5113.
[8] M.A. Bakht, M. Islam, A.A. Siddiqui, Ind. J. Het. Chem. 15 (2006) 297e298.
[9] W.e.i. Shi, X.u.h.o.n.g. Qian, R.o.n.g. Zhang, G.o.n.g.h.u.a. Song, J. Agric. Food
Chem. 49 (2001) 124e130.
[10] X.u.h.o.n.g. Qian, R.o.n.g. Zhang, J. Chem. Technol. Biotechnol. 67 (1996)
124e130.
[25] R.X. Wang, Y. Fu, L.H. Lai, J. Chem. Inf. Comput. Sci. 37 (1997) 615e621.
[26] R.X. Wang, Y. Gao, L.H. Lai, Drug Discov. Des. 19 (2000) 47e66.
[27] Y.H. Zhao, M.H. Abraham, J. Lee, A. Hersey, C.h.N. Luscombe, G. Beck,
B. Sherborne, I. Cooper, Pharm. Res. 19 (2002) 1446e1457.
[28] D.F. Veber, S.R. Johnson, H.Y. Cheng, B.R. Smith, K.W. Ward, K.D. Kapple, J.
Med. Chem. 45 (2002) 2615e2623.
[29] H.H.F. Refsgaard, B.F. Jensen, P.B. Brockhoff, S.B. Padkjaer, M. Guldbrandt,
M.S. Christensen, J. Med. Chem. 48 (2005) 805e811.
[30] I. Muegge, Med. Res. Rev. 23 (2003) 302e321.
[11] T.J. Hou, X.J. Xu, Curr. Pharm. Des. 10 (2004) 1011e1033.
[12] H.V. de Waterbeemd, E. Gifford, Nat. Rev. Drug Discov. 2 (2003) 192e204.
[13] T. Hou, J. Wang, W. Zhang, X. Xu, J. Chem. Inf. Model. 47 (2007) 460e463.
[14] C.A. Lipinski, F. Lombardo, B.W. Dominy, P.J. Feeney, Adv. Drug Deliv. Rev. 23
(1997) 3e25.
[15] A. Avdeef, Curr. Top. Med. Chem. 1 (2001) 277e351.
[16] T.T. Oprea, J. Comput. Aided Mol. Des. 16 (2002) 325e334.
[17] U. Norinder, A.S. Bergstr, Chem. Med. Chem. 1 (2006) 920e934.
[18] I.V. Tetko, V.Y. Tanchuk, J. Chem. Inf. Comput. Sci. 42 (2002) 1136e1145.
[31] P. Ertl, B. Rohde, P. Selzer, J. Med. Chem. 43 (2000) 3714e3717.
[32] <http://www.molinspiration.com>. 10/06/2008.
[33] R. Cruickshank, J.P. Duguid, B.P. Marmion, R.H.A. Swain, Medicinal Microbi-
ology, twelfth ed., vol. II, Churchill Livingstone, London, 1975, 196e202.
[34] A.H. Collins, Microbiological Methods, second ed. Butterworth, London, 1976.
[35] Z.K. Khan, In-vitro and in-vivo screening techniques for bioactivity screening
and evaluation, In: Proc. Int. Workshop UNIDO-CDRI, 1997. pp. 210e211.
[36] R.S. Varma (Ed.), Antifungal Agents: Past, Present and Future Prospects,
National Academy of Chemistry & Biology, Lucknow, India, 1998.