265
CHAPTER-V
SYNTHESIS OF 2-AZETIDINONES, THEIR
CHARACTERIZATION AND EVALUATION
OF THEIR PHARMACOLOGICAL
ACTIVITY FOR DIFFERENT PROFILES
266
Introduction
2-Azetidinones are also known as β-lactams which are derivatives of
1. Azetidine 2. Azetine 3. 2 Azetine and 4. Azete derived from
nitrogen derivatives of cyclobutane, cyclobutene and cyclobutadiene.
2-azetidinones have become popular because of their anti bacterial
properties. Eg: penicilines and cephalosporins.
Structure
2-azetidinone(1) is a solid having melting point 73-74°C it is water
sensitive and colorless in nature. Normally 2-azetidiones are low
melting oils or solids.
NH1
2
4
3
(a)
N
(b)
NH
(c)
N
(d)
R-N
O
R2
R1
Azetidin-2-one
R-N
R1
R2
O
Azetidin-3-one
R-N
R1
O
R2
Azetidin-4-one
N-R
O(1)
267
Azetidin-2-ones as an antibacterial agents
Priyadarshini et al8 have prepared azetidinones and evaluated them
for antibacterial property.
Freedy et al9 prepared certain substituted azetidinones and carried
out their antimicrobial activity.
Mulwad et al10 reported the synthesis and antimicrobial property of
cetain 4-hydroxycoumarin azetidinones.
NN
NN
SH
N
O Cl
R1
R1=2-Cl, 3-OCH3
Br
MeO CONH N
O Cl
Ar
Ar=phenyl
R3
R1
R2 O
OH
O
N
Cl
HO
R
R1=R2=R3=HR=4-NO2
268
John11 obtained certain useful azetidinone deravitives and reported
their bacteriostatic activity against both types of organisms.
Myer12 synthesized the following azetidin-2-ones and noted their
antibacterial action.
Spasov et al13 have reported synthesis and bactericidal property of
different 2-azetidinones.
Kolaus et al14 prepared several 2 azetidinones which were proved to
be bactericidal agents.
N
Z-NH
H
O
S
COOH
MeMe
Z=monoacyl
N
Z-NH
H
O
S
CH2OAc
MeMe
COOH
N
R
H
O
S
COOR1
CH3
CH3
R = H, Ph-CH2, t-Butyl, -OMeR1 = OH
N
R
H
O
S
COOMe
CH3
CH3
N
Ph R1
R O
R = Ph, P-CH3C8H4R1 = H or Ph
N
R R1
O CH3
N
R2
O
S
MeOOC COOMe
N
N=CHPh
R3
O
S Me
Me
R = N3R1 = CH3 or SC2H5R2 = H or COOCH3R3 = CH2-Ph, CH3, CH2C6H4OCH3
269
The following azetidin-2-ones were found useful against B. substilis
and Serratia mercense by Stejepan et al15
Bose16 carried out synthesis and anti microbial property of 2-
azetidinones.
Takashi et al17 synthesized approx 545 deravitives and proved to be
active against bacillus subtillis, E coli and S. aureus.
They18 also prepared 2-Azetidinones and carried out their
antibacterial evaluation.
N
O
O
NH
H
O
S {CH (NHAC) }n
R
R1
COOH
N
O
O
NH
H
O
Cl
R,R1 = H, CH3
CH-CH2-CH2-O
H2N
HOOC
NOH
CONH
N
O
HC
COOH
OH
N-R
R
O
N-R1
HR2
O
R-NH
N-CH
H
R-NH
OCOOH
OH
R=H2 or acyl; R1 = H; R2=H, CH2OH, aryl
270
Hassan et al19 prepared 2-Azetidinones and observed that these are
active antibacterial agents..
Osman et al20 prepared several 2-Azetidinones and evaluated their
antibacterial property.
Desai et al21 prepared 2-Azetidinones derived from thiadiazole and
screened from antibacterial property.
Diumo et al22 prepared certain 2-Azetidinones and shown their
antibacterial property (invitro) few deravitives shown marked
antabactarial property.
Bhat et al23 prepared group of 2-azetidinones and evaluated them for
antifungal antituberclar and antibacterial properties.
Udupi et al24 prepareded certain 2-Azetidinones and evaluated them
for antibacterial and anti-inflammatory property.
COOH
NO2
N
O
Ar
Ar
COOH
NO2
N
O
Ar
OAr
271
2-Azetidinones as fungicidal agents
Fungicidal25 activity was observed for 2-Azetidinones shown below
2-Azetidinones as effective antiviral drugs
Levinine et al26 synthesized certain 2- Azetidinones and carried out
their antiviral activity.
2-Azetidinones as cytotoxic agents
Takayanagi et al27 synthesized 2-azetidinones deravitives and carried
out the screening of cytotoxic activity.
CH2
S
N
N
O
H
C (COOCH2CCl3) C
Me
Me
CH2CONH
N
O
S
COOCH2CCl3
N
O
272
2-Azetidinones as anti-inflammatory drugs.
Piffer et al28 prepared large number of 2-Azetidinones and evaluated
them for anti inflammatory property.
Azetidinones of the following type has been synthesized and they
showed anti-inflammatory activity.
The compounds listed below showed anti-inflammatory property
proving their usefulness as anti-inflammatory agents.
Tandon et al29 prepared certain 2-Azetidinones and screened them
from different biological profiles.
1RN [CH2]mON
Cl Cl O
(CH2)n-R
m=2-5, n=0-4r= alkyl, cycloalkylR1=heteroalkyl
Cl N
Cl
Cl
O
CH2-CH2 N
NR'
Cl
(CH2)n R
ClO
n = 0-2R = dialkyl amines heteroaminesR' = aryl
NPh
ClCl
(CH2)3 NMe2
273
Azetidin-2-ones as anticonvulsant agents
Peter et al30 prepared several 2-Azetidinones and evaluated their
anticonvulsant property.
2-Azetidinones as hypotensive drugs
several 2-Azetidinones and 3-Azetidinones have been prepared and
screened against hypotensic property31-33
2-Azetidinones as hypnotics
Maffi34 synthesized several 2-azetidinones and reported their hypnotic,
sedative and anticonvulsant activity.
Cl N
O
R
Cl N
O
R
ClR = Benzoyl
Cl
Cl N
O
O
Cl N
O
O
N
HO Me
MeR1
RON
O Me
Me
RR1
R=H, CH3, C2H5, C(CH3)3R1=H, Ph
N
O
R
R1
R2
R=H, CH3, C2H5, Cyclohexyl, Ph, p-NO2 Ph, p-NH2PhR1=Ph, PhCH2, R2 : H, CH3, C2H5
274
Testa et al35-36 prepared certain disubstituted 2-azetidinones and
reported thier sedative property.
Emilio et al synthesized 2-Azetidinones and carried out thier
evaluation of central nervous system stimulant activity.
2-Azetidineones as an anti tubercular agent
Parekh et al37 reported synthes of certain 2-azetidinones bearing
Benzimidazole moiety and carried out their antimycobacterial activity.
Udupi et al38 synthesized certain 2-azetidinones from naproxen and
carried out their antimycobacterial and antimicrobial studies.
Pai et al39 carried out their work on the preparation and
pharmacological property of 2-azetidinones. The synthesized
N-R2
O
R1
R
O
R = HR1 = cyclohexylR2=H
NH
N
CO NH N
O Cl
R
R=aryl
MeO
CHCONH
CH3
N
O
Ar
Ar MeO
CHCONH
CH3
N
O
Ar
OAr
275
compounds were evaluated for antimicrobial and antifungal property.
The deravitives shown to posses significant antibacterial property and
not active as fungal agents.
Bhat et al40 carried out preparation and study on their antibacterial
property of some azetidinone derivatives with the p-anisidine moiety.
The antibacterial and antifungal potential of the synthesized
compounds were evaluated the compounds exhibited significant
antimicrobial activity.
HOOC S
N
NH C CH2 NH
O
N C H
R
ClO
HN
OCH3
H2C C
HN N
O
Cl
R
O
276
OHC
(1)
N
CH2-CH3
CH2-CH3
Scheme-1
2) (25% aq)
N
CH3-CH2
CH3-CH2
CH N N
Z - COCl, TEA
(2)
N
CH3-CH2
CH3-CH2
CH N N
Z O
BL1 - BL-16
1) N,N-Diphenyl hydramine HCl,ethanol room temp.
277
Synthesis of Schiff Base (4–Diethyl amino benzaldehyde diphenyl
hydrazone)
A mixture of alcohol (25 ml) and diethyl amino benzaldehyde (8gms,
0.0452mol) was taken in a 250 ml R.B. flask. The mixture was stirred
until a homogenous solution was obtained. N,N–Diphenyl hydrazine
hydrochloride (10gm, 0.0454mol) was added with stirring. (As the
reaction is exothermic it should be carried out by placing R.B. flask in
a freezing mixture). Reaction mass is stirred for another 45 min.
Ammonia solution (5ml) was added over a period of 1hr at 300C
without external cooling. 4-Diethylaminobenzaldehyde
diphenylhydrazone was precipitated out. Cool the reaction mass to
50C with stirring. The isolated crude produt is purified by washing in
petroleum ether (60:95).
Preparation of acid chlorides:
The mixture of Aryl/Aryloxy acids, thionyl chloride and benzene was
reflexed for 2 hours. The excess of thionyl chloride was eliminated and
product was used for further step. The aryloxy acids required were
prepared from the corresponding phenol derivatives by known
method.
278
Synthesis of azetidin-2-ones (BL1–BL16)
The solution of Schiff base in anhydrous benzene and acid chloride
was taken in round bottom flask. To this few drops of triethyl amine
was added and heated for 2 hours . The solid cake formed was filtered
and concentration of the filtrate was carried out to obtain solid
residue which was purified by crystallization from ethyl alcohol.
Similar technique is used for obtaining remaining compounds. TLC
technique is used to confirm the purity mobile phase used was n-
hexane and ethyl acetate (ratio 8:2 v/v). The characteristic data of the
synthesized 2-azetidinones is presented in the table No 40.
279
Table 40: Characterization data of 2-Azetidinones
Sr.No.
Code Z mol. formulam.p.(°C)
yield(%)
01. BL1 Phenoxy C31H31O2N3 78-80
02. BL2 2–(2’,6’-dichloro anilino)phenyl C37H34ON4Cl2 80
03. BL3 4–Isobutyl phenyl C36H41ON3 86
04. BL4 2–Methyl phenoxy C32H33O2N3 68
05. BL5 2–Chloro phenoxy C31H30O2N3Cl 88-90
06. BL6 3–Chloro phenoxy C31H30O2N3Cl 58
07. BL7 4–Chloro phenoxy C31H30O2N3Cl 70
08. BL8 2–Chloro phenyl C31H30ON3Cl 86
09. BL9 2,4–Dichloro phenoxy C31H29O2N3Cl2 74
10. BL10 4–Methyl phenoxy C32H33O2N3 60
11. BL11 4–Amino phenoxy 94
12. BL12 3–Methyl phenoxy C32H33O2N3 76
13. BL13 4–Bromo phenoxy C31H30O2N3Br 100
14. BL14 4–Nitro phenoxy C31H30O4N4 70
15. BL15 2–Nitro phenoxy C31H30O4N4 72
16. BL16 Diphenyl C37H35ON3 60
N
CH3-CH2
CH3-CH2
CH N N
Z O
280
Spectral Data For 2-Azetidinones
Spectral data of Schiff Base (SB)
IR (KBr) CM-1:IR spectrum of Schiff base (SB) showed its characteristic absorption
bands in the following region.
3040 (Aromatic C-H Str), 2970 & 2893 (C-H Str of CH3 asymmetric
and symmetric) 2928 and 2866 (C-H Str of CH2 asymmetric and
symmetric) 1607 (C=N), 1596,1522,1495 (C=C ring Str), 1455 and
1375 (C-H bending of CH3 asymmetric and symmetric) , 1426 and
1354 (C-H bending of CH2 group, asymm and symm), 819(p-
substituted benzene ring) 740 (mono substituted phenyl)
1H NMR : ( ppm)
The 1HNMR data for Schiff base (SB) exhibited its peaks at
1.124-1.194 (6H,t, 2XCH3), 3.11 – 3.416 (4H,q,2XCH2)
6.606-7.488 (15H,m,14H of Ar-H and 1H of N=CH)
N
CH2
CH2
H3C
H3C
CH=N N
281
282
283
Spectral Data for BL-2
IR (KBr) CM-1:IR spectrum of 2-azetidinone (BL-2) showed its characteristic
absorption bands in the following region.
3430, 3040 (Ar. C-H. Str), 2970 & 2870 (C-H Str of CH3 group), 2930
& 2830 (C-H Str of CH2 group), 1708 (C=O of Betalactum)
1597,1521,1495(C=C ring Str), 1455 and 1355 (C-H bending of CH3
and CH2), 1299 (C-N), 880 (substituted phenyl ring), 818.8 (p-
substituted benzene ring) 746 (mono substituted phenyl ring)
541.63(C-Cl)
1H NMR : ( ppm)
The 1HNMR data for 2-Azetidinone (BL-2) exhibited its peaks as below
1.12-1.26 (6H,t,2XCH3), 3.1 (1H,s,H of N-CH of Betalactum ring), 3.4
(4H,q,2XCH2) 6.2 (1H,s,1H of C=O-CH of Azetidine ring), 6.5(1H,s,NH),
6.66-7.56 (21H,m,Ar-H)
N
CH2
CH2
H3C
H3C
CH N
O
N
NH
ClCl
284
13C NMR of BL-2
13CNMR13CNMR Spectrum of BL-2 gave the signal for its 37 magnetically
different environmental carbon atoms as indicated below.
C13 – 147.79C21&C25 – 144.23C20 – 137.29C51, C19 – 135.26C26, C32 – 133.00C6, C10 – 132.62C7, C9 – 130.95C27&C31 – 129.57C28&C30 – 127.73C34&C36 – 124.00C33&C37 – 123.10C8, C14 – 119.23C22, C24 – 118.00C23, C35 – 116.85C15, C18, C17 – 115.00C16, C29 – 108.00C2 – 45.84C3 – 44.45C1&C4 – 12.5C11 – 11.11C12 – 8.57
Mass Spectra:The massspectra of (BL-2 molecular wt. 621) showed parent ion peak
at m/e 621. The base peak is at m/e 559, other important daughter
ions are m/e 255, 219,130.9,97.
1 2
3 4 5
6 7
8
910
11
1213
1415
16
1718
19
20
21
22
2324
25
2627
28
2930
31
3233
34
3536
37
N
CH2
CH2
H3C
H3C
CH N
O
N
NH
ClCl
285
286
287
288
289
Spectral Data for BL-13
IR (KBr) CM-1:IR spectrum of 2-Azetidinone (BL-13) showed its characteristic
absorption bands in the following region. 3041 (Ar. C-H Str)
2970,2931,2830 (C-H Str of CH3 and CH2) 1678 (C=O)
1597,1521,1495 (C=C ring Str) 1400 and 1355. (C-H bending of
CH3&CH2) 1055 (C-H-O) 819 (p-disubstituted benzene) 747-
(monosubstituted benzene ring) 625 (C-Br)
1H NMR : ( ppm)
The 1H NMR data of 2-Azeidinone (BL-13) exhibited its peaks at.
1.12 – 1.32 ( 6H,t, 2XCH3) 3.36-3.49 (4H,q, 2XCH2), 4.58 (1H,s, CH
of N-CH of Betalactum ring), 4.65 (1H,s, 1H of O-CH of Betalactum
ring), 6.72,8.57 (18H,m, Ar-H)
N
CH2
CH2
H3C
H3C
CH N
OO
N
Br
290
Mass Spectrum (Mol. Wt. 556)
The mass Spectrum of (BL-13 Mol Wt. 556) showed a parent ion peak
at m/e 556. The base peak is observed at m/e 344 other prominent
daughter ions are seen at m/e 176,161,149.
N
CH2
CH2
H3C
H3C
CH N
CH
OO
N
Br
m/e = 556
1)
2)
N
CH2
CH2
H3C
H3C
CH2 N N
m/e = 344
3)N
CH2
CH2
H3C
H3C
CH2 N
m/e = 176
4)N
CH2
CH2
H3C
H3C
CH
m/e = 161
5)N
CH2
CH2
H3C
H3C
m/e = 149
291
292
293
294
Spectral Data for BL-1
IR (KBr) CM-1:IR spectrum of 2-Azetidinone (BL-1) showed its characteristic
absorption bands in the following region.
3040(Ar-C-H Str), 2969-2866 (C-H Str of CH2 and CH3 groups), 1697
(C=O of Betalactum ring), 1607, 1596, 1494.69 (C=C ring Str), 1426-
1375 (C-H bending of CH3), 1456 (C-H bending of CH2), 1375(C-N),
1055 (C-O-C), 818 (p- substituted benzene ring), 748.69 (mono
substituted benzene ring)
N
CH2
CH2
H3C
H3C
CH N
CH
OO
N
295
296
Spectral Data for BL-3
IR (KBr) CM-1:IR spectrum of 2-azetidinone (BL-3) showed its characteristic
absorption bands in the following region. 3040.54 (Aromatic C-H Str),
2970 and 2870 (C-H Str of asymmetric and symmetric of –CH2 group),
2930 and 2830 (C-H Str of asymmetric and symmetric of –CH2 group),
1708 (C=O of betalactum ring) 1596, 1521, 1495 (C=C ring Str), 1455
and 1354, 1375 (C-N), (C-H bending of CH3 and CH2 groups), 818 (p-
substituted benzene ring), 747 (mono substituted benzene ring)
Mass Spectrum (Mol. Wt: 531)
The mass spectrum of (BL-3, Mol. Wt. 531) didnt show a parent ion
peak at m/e 531. May be due to decomposition of Betalactum ring.
However the base peak was observed at m/e 344.2
N
CH2
CH2
H3C
H3C
CH N
O
N
H3C
CH2 CH
CH3
CH3
N-CH-N=N
CH2
CH2
H3C
H3C
297
298
299
Spectral Data for BL-4
IR (KBr) CM-1:IR spectrum of 2-Azetidinone (BL-4) showed its characteristic
absorption bands in the following region. 3040 (Ar-C-H Str), 2970 &
2870 (C-H Str of –CH3 group asymmetric & symmetric), 2930 & 2830
(C-H Str of –CH2 group asymm and symm) 1708 (C=O of Betalactum
ring) 1597, 1521, 1495 (C=C ring Str), 1375 & 1321(C-H bending of –
CH3 and –CH2 groups), 880 (substituted phenyl ring) 819 (p-
substituted benzene ring), 787 (mono substituted benzene ring)
Spectral Data for BL-11
IR (KBr) CM-1:IR spectrum of 2-Azetidinone BL11 showed its characteristic
absorption bands in the following region.
3400 (Broad band, NH2 Hydrogen banded), 3060 (Ar C-H Str) 2973,
2870 (C-H Str of CH3 and CH2 groups), 1698 (C=O of Betalactum
ring), 1596, 1521, 1494 (C=C ring Str), 1376 (C-N), 1494 & 1355 (C-H
bending of CH3 and CH2 groups) 1055 (C-O-C), 819.2 (p-substituted
benzene ring), 747.67 (monosubstituted benzene ring)
N
CH2
CH2
H3C
H3C
CH N
OO
CH3
N
N
CH2
CH2
H3C
H3C
CH N
CH
OO
N
NH2
300
Spectral Data for BL-14
IR (KBr) CM-1:IR spectrum of 2-Azetidinone BL-14 showed its characteristic
absorption bands in the following region.
3040 (Ar C-H Str), 2970 & 2870 (C-H Str of CH3 asymm & symm),
2930 & 2840 (C-H Str of –CH2 group asymm & symm), 1758 (C=O of
Betalactum ring) 1596, 1521, 1494 (C=C ring Str), 1521 & 1354 (NO2),
1494, 1375 (C-H bending of CH3 and CH2 groups), 1054.64 (C-O-C),
818.97 (P-disubstituted benzene ring), 747.62 (monosubstituted
benzene ring)
N
CH2
CH2
H3C
H3C
CH N
OO
N
NO2
301
302
303
304
Anti-Bacterial Activity of 2-Azetidinones
The invitro antibacterial screening was carried out at microbiology
department at Navodaya Medical College and Research Centre,
Raichur. The same procedure was used for antibacterial testing as
described in Chapter-III. The results are presented in Table No. 41
Sr.No. Sample No.
Zone of Inhibition (mm)Staphylococcus
aureus E.Coli Pseudomonasaeruginosa
1 BL1 00 30 00
2 BL2 20 34 00
3 BL3 00 32 00
4 BL4 00 34 00
5 BL5 42 34 00
6 BL6 00 32 00
7 BL7 -- -- --
8 BL8 00 32 00
9 BL9 22 24 00
10 BL10 00 34 00
11 BL11 00 30 00
12 BL12 -- -- --
13 BL13 00 28 00
14 BL14 00 28 00
15 BL15 00 34 00
16 BL16 22 30 00
17 Ciprofloxacin 30 28 27
18 Gentamycin 34 30 3519 Tobramycin 30 32 34
305
Results and Discussion
All the deravitives of the 2-azetidinone series were evaluated for
antibacterial studies against the organisms Staphylococcus aureus,
E.coli and Pseudomonas aeruginosa at the Conc 10 µg/ml.
Ciprofloxacin, Gentamycin and Tobramycin of Conc 10 µg/ml were
used as reference drugs for comparison. Majority of the deravitives
showed significant antibacterial property against the organism E.coli.
The compounds BL9 showed medium activity while remaining
deravitives exhibited much significane activity as compared with the
standard drugs. None of the deravitives in this group showed activity
against Pseudomonas aeruginosa. The compound BL5 showed
significane activity against Staphylococcus aureus, where as BL2, BL9
and BL16 exhibited moderate activity. Rest of the compounds in this
series did not show activity.
306
Anti-Fungal Activity of 2-Azitidinones
The invitro antifungal activity of the Azitidinones synthezied was
carried at Maratha Madals Nathaji Rao Dental college and Research
Centre, Belgaum recognized by Rajiv Gandhi University of Health
Sciences, Bangalore as nodal centre for carrying out biological
evaluation.
Table 42: Antifungal Activity of Azetidinones
Sr.No. Compounds
Concentration (µg/ml)
75 50 25 10
1 BL-1 R R R R
2 BL-2 R R R R
3 BL-3 R R R R
4 BL-4 R R R R
5 BL-5 R R R R
6 BL-6 18mm 16mm 16mm R
8 BL-8 26mm R R R
9 BL-9 740mm 740mm 38mm 32mm
10 BL-10 16mm 14mm R R
11 BL-11 14mm 14mm 12mm R
13 BL-13 18mm 16mm 12mm R
14 BL-14 22mm 20mm 18mm 14mm
15 BL-15 R R R R
16 BL-16 R R R R
307
Results and Discussions
Among the 2-azitidinones series of compounds (BL1 - BL16), only BL9
has shown excellent activity. The compounds BL6, BL11, BL13 and
BL14 showed moderate activity and remaining deravitives of this
group have not shown any antifungal activity at all the
concentrations. Thus the synthetic β-lactum series of compounds as
expected failed to show antifungal activity against the standard drug
at all concentration levels used for the study.
Anticancer Activity of 2-Azetidinones
The anticancer activity of representative compounds of 2-azetidinone
were carried out in the department of microbiology at Maratha
Mandal’s Nathaji Rao Dental college and Research Centre, Belgaum.
During the present work selected few representative compounds of 2-
azetidinones namely BL3, BL9, BL10, BL14 and BL16 were evaluated
for anticancer activity as described in the previous chapter (IIIA).
308
Table 43: MTT Assay Results (IC50 Values) of 2-Azetidinones
Sr.No
CompoundCode
Hela Cell Line(HumanCervix) A-549-Human Lung Carcinoma
10 μl 20 μl 30 μl Average 10 μl 20 μl 30 μl Average
01 BL3(ATC11) 35.35 34.46 32.64 34.15 29.34 26.45 25.1 26.96
02 BL9(ATC15) 36.15 32.76 25.82 31.57 112 114.86 124.96 117.27
03 BL10(ATC14) 121.54 132.6 132.76 128.96 118.76 12.48 128.26 86.5
04 BL14(ATC13) 36.76 32.32 29.7 32.926 37.68 30.98 31.11 33.25
05 BL16(ATC12) 37.16 35.47 34.38 35.67 29.18 26.52 25.16 26.95
Table 44
Sr.No.
CompoundCode
MDA-MB Human Adino carcinomaMammary gland
HT-29 Human Colorectal Adenocarcinoma
10 μl 20 μl 30 μl Average 10 μl 20 μl 30 μl Average
1 BL3(ATC11) 28.68 27.34 26.86 27.62 28.18 26.46 25.68 26.77
2 BL9(ATC15) 38.46 36.86 36.24 37.18 31.48 29.82 28.98 30.09
3 BL10(ATC14) 108.64 102.84 39.84 83.77 99.98 92.64 91.88 94.83
4 BL14(ATC13) 34.26 31.48 31.08 32.273 32.64 30.88 30.26 31.26
5 BL16(ATC12) 29.56 27.86 27.28 28.23 28.84 26.58 25.46 26.96
309
Figure 2: Graph Showing IC 50 Values of 2-Azetidinone compounds
I C 5 0 v a lu e s a g a in s tH e la C e l l l in e s ( H u m a n C e r v ix )
)11
(ATC
3BL
)15
(ATC
9BL
)14
(ATC
10BL
)14
(ATC
14BL
)12
(ATC
16BL
0
5 0
1 0 0
1 5 0
2 - A z e t id in o n e C o m p o u n d s
IC50
valu
es
I C 5 0 v a lu e s a g a in s tA -5 4 9 -H u m a n L u n g C a rcim o m a
) 11(AT
C3
BL
) 15(AT
C9
BL
) 14(AT
C10
BL
) 14(AT
C14
BL
) 12(AT
C16
BL
0
50
100
150
2 -A ze t idin o n e C o m po u n ds
IC50
valu
es
I C 5 0 v a l u e s a g a i n s t M D A - M B H u m a n A d i n o C a r c i n o m a m a m m a r y G l a n d
) 11(AT
C3
BL
) 15(AT
C9
BL
) 14(AT
C10
BL
) 14(AT
C14
BL
) 12(AT
C16
BL
0
2 0
4 0
6 0
8 0
1 0 0
2 - A z e t i d i n o n e C o m p o u n d s
IC50
value
s
I C 5 0 v a l u e s a g a i n s t H u m a nC o l o r e c t a l A d e n o C a r c i n o m a
) 11(AT
C3
BL
) 15(AT
C9
BL
) 14(AT
C10
BL
) 14(AT
C14
BL
) 12(AT
C16
BL
0
2 0
4 0
6 0
8 0
1 0 0
2 - A z e t i d i n o n e C o m p o u n d s
IC50
value
s
310
Results & Discussions:
Except BL-10 all other 2-Azetidinone derivative like BL-3, BL-9, BL14
and BL16 showed potent anti cancer activity against the cell line. Hela
(Human Cervix). The same 2-azetidinone derivatives when screened
against A549 Human lung carcinoma cell line showed that BL-9 which
was potent against Hela cell line was inactive. Further the derivatives
like BL-3, BL14 and BL16 exhibited much significant activity and the
derivative BL-10 showed moderate activity against the same cell line.
In contrast to the compounds belonging to triazole thiadiazoles all the
2-azetidinone derivatives screened showed anticancer activity against
MDA-MB Adeno Carcinoma (Mammary gland) surprisingly all the
derivatives namely BL3, BL9, BL14, BL16 showed potent anti cancer
activity, where as the BL10 showed moderate activity against the HT-
29 Human Colorectal Adeno Carcinoma. The anti cancer results of the
compounds fallow the same pattern against HT-29 Human Colorectal
Adeno carcinoma. In comparison it can be said that the 2-azetidinone
derivatives having -lactum ring posses potent activity than the
triazole thiadiazole.
311
Anti Inflammatory and analgesic activity of 2-Azetidinones
The Antiinflammatory and analgesic activity was carried out at
Navodaya Medical College & Research Centre, Raichur, Karnataka
following the same procedure as described in Chapter-IIIB.
Table 45: Anti-inflammatory Activity of 2-Azetidinones
Result: The compounds showed weak activity as compared with the
standard.
Sl.No Treatment
Percentage inhibition of rat’s hind paws Oedema atdifferent time intervals
30min 1 hr 2 hr 4 hr 6 hr 8 hr
01 Control 0.00 0.00 0.00 0.00 0.00 0.00
02 DiclofenacSodium 18.47 19.94 19.81 36.76 38.08 36.36
03 SB 17.39 32.63 21.62 4.41 4.76 4.95
04 BL2 4.34 24.21 30.63 6.61 7.14 7.43
05 BL3 11.95 28.425 27.92 4.41 4.67 4.95
06 BL5 9.80 34.75 37.84 37.84 0.80 4.96
07 BL6 4.34 9.48 9.01 2.95 0.81 2.47
08 BL7 8.70 30.5 33.33 11.76 7.14 4.95
09 BL10 32.62 37.91 20.74 8.83 0.01 3.31
10 BL14 17.40 32.64 21.64 4.42 4.76 4.96
312
Table 46: Analgesic Activity of 2-Azetidinones
Result: The compounds exhibited weak to moderate analagesic activity.
Sl. No TreatmentMean +- S.E.M
0 hr 30min 1 hr 2 hr 4 hr 6 hr 8 hr
01 Control
02 Pentazocin 6.24+0.889 12.87+1.33 12.91+1.32 13.87+0.279 13.65+0.85 11.83+1.04 11.83+1.04
03 SB 5.83+0.60 7.16+0.48 4.66+0.49 4.33+0.49 5.50+0.56 4.16+0.48 5.50+1.06
04 BL2 5.33+0.49 8.66+1.14 4.50+0.43 4.00+0.52 5.00+0.58 5.00+0.58 4.16+0.91
05 BL3 5.66+0.56 6.83+0.83 4.83+0.70 4.50+0.88 4.50+0.43 4.33+0.49 4.66+0.61
06 BL5 5.33+0.49 5.16+0.40 3.33+0.67 3.16+0.17 4.33+0.49 3.00+0.26 5.16+1.17
07 BL6 4.50+0.43 5.16+0.70 3.502+0.43 4.16+0.60 5.16+0.94 4.83+0.94 3.66+0.33
08 BL7 5.66+0.67 5.50+0.50 4.83+0.83 3.33+0.21 4.50+0.56 5.00+0.86 4.16+0.65
09 BL10 6.00+0.58 3.50+0.43 3.80+0.31 3.10+0.40 3.33+0.33 3.33+0.33 3.33+0.33
10 BL14 5.82+0.60 7.17+0.48 4.65+0.49 4.33+0.49 5.50+0.56 4.17+0.50 5.50+1.06
313
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