Synthesis, antioxidant and antimicrobial evaluation of thiazolidinone, azetidinone encompassing indolylthienopyrimidines

Article abstract of DOI:10.1007/s12039-011-0180-6

Various 2-amino-N′-{3-(2′,5′-disubstituted-1H-indol- 3′-yl)methylene}-4,5-dimethylthieno-3- carbohydrazides (3) synthesized by condensation of 2-amino-4,5-dimethyl thiophene-3-carbohydrazide (2) with 2,5- disubstituded indole-3-carboxaldehyde (1). The Sch

Full text of DOI:10.1007/s12039-011-0180-6

c
J. Chem. Sci. Vol. 124, No. 2, March 2012, pp. 469–481. ꢀ Indian Academy of Sciences.
Synthesis, antioxidant and antimicrobial evaluation of thiazolidinone,
azetidinone encompassing indolylthienopyrimidines
ANAND RAGHUNATH SAUNDANE∗, MANJUNATHA YARLAKATTI,
PRABHAKER WALMIK and VIJAYKUMAR KATKAR
Department of Post-Graduate Studies and Research in Chemistry, Gulbarga University,
Gulbarga-585 106, India
e-mail: arsaundane@rediff.com
MS received 26 March 2011; revised 22 July 2011; accepted 8 August 2011
Abstract. Various 2-amino-Nꢁ-{3-(2ꢁ,5ꢁ-disubstituted-1H-indol-3ꢁ-yl)methylene}-4,5-dimethylthieno-3-
carbohydrazides (3) synthesized by condensation of 2-amino-4,5-dimethyl thiophene-3-carbohydrazide (2)
with 2,5- disubstituded indole-3-carboxaldehyde (1). The Schiff’s base (3) on cyclocondensation with acetic
anhydride and triethyl orthoformate afforded thienopyrimidine analogues (4) and (7), respectively. Compounds
4 or 7 on cyclization with thioglycolic acid and chloroacetyl chloride gave thiazolidin-4-ones (5) or (8) and
azitidin-2-ones (6) or (9) respectively. The structures of these newly synthesized compounds have been estab-
lished on the basis of their spectral data and elemental analysis. Some of the compounds exhibited promising
antioxidant and antimicrobial activities.
Keywords. Indole; thienopyrimidine; thiazolidin-4-one; azetidin-2-one; antioxidant; antimicrobial activities.
1. Introduction
have shown good efficiency, their use has been limited
because of their possible detrimental effect on human
health.6 As a consequence, there is a growing interest
in the development of new antioxidants that are based
on natural components and with low toxicity.
The complex sequence of cellular and molecular
changes that take place during cancer formation are
mediated by the different endogenous and exogenous
stimuli.1 Among endogenous stimuli are intermediates
of oxygen reduction, i.e., oxygen free radicals (OFR),
or more generally, reactive oxygen species (ROS),
which interact with DNA, forming various aducts.
OFRs are important in the pathogenesis of many dif-
ferent diseases.2–5 ROS are also involved in the pro-
cesses of aging. In food, rancidity is one of the major
concerns and is mainly related to oxidative degradation
of polyunsaturated fatty acids. For years, antioxidants
have been used to prevent the degradation of food.6
Phenolic derivatives are one of the most effective and
commonly used antioxidants. These derivatives slow
down the degradation of food ingredients by inhibiting
their oxidation.7,8 Among this family of compounds,
both synthetic antioxidants for example BHT, BHA,
TBHQ and natural ones such as tocopherols, phenolic
acids, and herbal extracts are used to protect against
oxidative degradation. Although synthetic antioxidants
Heterocyclic compounds are highly ranked among
pharmaceutically important natural and synthetic mate-
rials. The remarkable ability of heterocyclic nuclei to
serve as both biomimetics and active pharmacophores
has largely contributed to their unique value as tra-
ditional key elements of numerous drugs. It is well
known that, indole derivative extensively present in nat-
ural products, are very important substances for their
medicinal and biological aspects. Malatonin (MLT)9 is
a highly conserved molecule that it acts as a free radi-
cal scavenger and a broad spectrum antioxidant.10 It is
known to be a potent in vitro antioxidant as well as power-
ful in vivo radical scavenger. Indole nucleus is frequent-
ly found in medicinal chemistry and is considered as
privileged scaffolds. Indole analogues constitute an
important class of therapeutic agents in medicinal che-
mistry including anticancer,11 antioxidant,12 anti-
rheumatoidal,13 anti-HIV,14 and also play a vital role in
the immune system.15,16 Many indole derivatives con-
sidered as the most potent scavengers of free radicals.17
The thiophene ring is bioisosteric replacement for
the phenyl group broadly present in active drugs, the
thiophene core exists in many natural and synthetic
∗For correspondence
469

470
Anand Raghunath Saundane et al.
pharmaceuticals,18,19 tuberculosis20 and antimicrobial 2.1 2-Amino-4,5-dimethyl-thiophene-3-carbohydrazide (2)
drugs.21
2-Amino-4,5-dimethyl-thiophene-3-carbohydrazide (2)
The molecular manipulation of promising lead com-
pounds is still a major line of approach to develop
new drugs. It involves an effort to combine the sepa-
rate pharmacophoric groups of similar activity into one
compound, thus making structural changes in the bio-
logical activity. As reported earlier the thiazolidinone
ring present in a large number of biologically active
molecules of different pharmacological classes exhib-
ited different activities. The historical importance of thi-
azolidine derivative, i.e., the development of penicillin
which shows the presence of thiazoline ring. There has
been substantial interest in the chemistry of thiazolidin-
was prepared by following reported method.45
2.2 2-Amino-4,5-dimethyl-3-{N1-[(2ꢁ-phenyl-5ꢁ-substituted
1H-indol-3ꢁ-yl)methylene]}thieno-3-carbohydrazides
(3a–c)
A mixture of hydrazide (2) (0.001 mol) and the respec-
tive 2,-phenyl-5-substituted indole-3-caroxaldehydes46
(1 a–c) (0.001 mol) in ethanol (30 ml) was refluxed for
3 h and then left to cool. The solid formed was col-
lected by filtration and recrystallized from ethanol to
4-one ring systems, which is the core structure in a vari- give compounds 3a–c.
ety of synthetic pharmaceuticals with a broad spectrum
of biological activity,22 such as anti-mycobacterial,23
2.2a 2-Amino-4,5-dimethyl-3-{N1-[(2ꢁ-phenyl-5ꢁ-chloro-
antifungal,24 anti-cancer,25 anti-tuberculosis,26 anti-
convulsant,27 anti-edematous,28 anti-diarrhea,29 anti-
HIV,30,31 anti-platelet-activating factor,32 antidiabetic,33
antihistaminic,34 cyclooxygenase inhibitors, lipoxyge-
nase inhibitors,35 anti-inflammatory and analgesic36
activity. In addition, a large number of antibiotics con-
tain the 2-azetidinone (commonly known as β-lactam)
moiety37 such as penicillin, cephalosporin and car-
bapenem. It is also associated with a variety of thera-
peutic activities.38–42
1H-indol-3ꢁ-yl)methylene]}thieno-3-carbohydrazide (3a):
Yellow powder, Yield 0.31 g (72%), m. p. 125–126◦C;
IR (KBr) ν cm−1 3404 (NH2), 3301 (indole NH), 3170
1
(NH), 1645 (CO), 1598 (C=N); H NMR (500 MHz,
DMSO-d6) δ 11.5 (s, 1H, indole NH), 9.9 (s, 1H, NH),
8.9 (s, 1H, CH=N), 7.1–8.0 (m, 10H, 8 ArH and NH2),
2.7 (s, 3H, 5-CH3), 2.3 (s, 3H, 4-CH3); 13C NMR
(125 MHz, DMSO-d6): δ 13.4, 14.1, 114.1, 121.5,
122.5, 125.6, 126.7, 128.5, 129.3, 130.1, 133.2, 134.3,
134.6, 134.9, 138.2, 140.2, 142.6, 142.7, 168.2, 171.2;
EI-MS; m/z 422, 424; Anal. calcd. for C22H19N4OSCl:
C 62.56; H, 4.50; N, 13.27. Found: C,62.77; H4.33; N,
13.51.
Due to the diversified nature of indole, thienopyrimi-
dine, thiazolidin-4-one and 2-azetidinones which render
them useful substance in drug research. In continuation
of our search for novel biologically active indole deriva-
tives,43,44 in this paper we report the synthesis, antiox-
idant and antibacterial activities of the title compounds
and its derivatives.
2.2b 2-Amino-4,5-dimethyl-3-{N1-[(2ꢁ-phenyl-5ꢁ-methy3–
1H-indol-3ꢁ-yl)methylene]}thieno-3-carbohydrazide (3b):
Yellow powder, Yield 0.281 g (70%), m. p. 144–145◦C;
IR (KBr) ν cm−1 3406 (NH2), 3309 (indole NH), 3176
1
(NH), 1645 (CO) 1599 (C=N); H NMR (500 MHz,
DMSO-d6) δ 11.4 (s, 1H, indole NH), 9.8 (s, 1H, NH),
8.9 (s, 1H, CH=N), 7.0–8.0 (m, 10H, 8 ArH and NH2),
2.8 (s, 3H, 5-CH3), 2.5 (s, 3H, 5ꢁ-CH3), 2.2 (s, 3H, 4-
CH3); 13C NMR (125 M Hz, DMSO-d6): δ 13.5, 14.3,
24.2, 114.5, 122.0, 123.1, 125.1, 126.9, 128.8, 129.7,
130.4, 133.6, 134.3, 134.6, 134.9, 140.0, 140.7, 142.0,
143.1, 168.6, 171.6; Anal. calcd. for C23H22N4OS: C
68.66; H, 5.47; N, 13.93. Found: C, 68.47; H, 5.29; N,
14.05.
2. Experimental
All the reagents were obtained commercially and used
by further purification. Melting points were determined
by an open capillary method and are uncorrected.
The IR (KBr) spectra were recorded with a Perkin-
1
Elmer spectrum one FT-IR spectrometer. The HNMR
(500 MHz) and 13C NMR (125 MHz) (DMSO-d6) spec-
tra recorded with an Bruker NMR (500 Mz) and the
chemical shifts were expressed in ppm (δ scale) down-
field from TMS. Mass spectra were recorded with a
JEOL GCMATE II GC-MS mass spectrometer. Ele-
mental analysis carried out using Flash EA1112 series
elemental analyzer.
2.2c 2-Amino-4,5-dimethyl-3-{N1-[(2ꢁ-phenyl-5ꢁ-1H-
indol-3ꢁ-yl)methylene]}thieno-3-carbohydrazide (3c):
Yellow powder, Yield 0.275 g (71%), m. p. 130–131◦C;
IR (KBr) ν cm−1 3402 (NH2), 3305 (indole NH), 3172
1
(NH), 1648 (CO) 1602 (C=N); H NMR (500 MHz,

Synthesis, antioxidant and antimicrobial evaluation of thiazolidinone, azetidinone encompassing
471
DMSO-d6) δ 11.3 (s, 1H, indole NH), 9.8 (s, 1H, NH), (s, 3H, 5-CH3); EI-MS; Anal. calcd. for C22H20N4OS:
8.8 (s, 1H, CH=N), 7.1–7.9 (m, 11H, 9 ArH and NH2), C 69.90; H, 4.85; N, 13.59. Found: C, 70.03; H, 4.97;
2.7 (s, 3H, 5-CH3), 2.4 (s, 3H, 4-CH3); Anal. calcd. for N, 13.45.
C22H20N4OS: C 68.04; H, 5.14; N, 14.43. Found: C,
68.13; H, 5.27; N, 14.29.
2.4 2,5,6-Trimethyl-3-[2-(2ꢁ-phenyl-5ꢁ-substituted 1H-
indol-3ꢁ-yl)-4-oxothiazolidin-3-yl]thieno[2,3-d]pyrimidin-
2.3 2,5,6-Trimethyl-3-[(2ꢁ-phenyl-5ꢁ-substituted 1H-
indol-3ꢁ-yl)methyleneamino]thieno[2,3-d]pyrimidin-
4(3H)-ones (4a–c)
4(3H)-ones (5 a–c)
To a solution of compound 4 in methanol containing
catalytic amount of anhydrous zinc chloride, thiogly-
Compound 3 (0.001 mol) in acetic anhydride (18 ml) colic acid (0.001 mol) was added drop-wise at room
were heated under reflux for 6 h and cooled to room temperature and the reaction mixture was refluxed for
temperature. The precipitated solid was collected and 10 h the excess methanol was distilled off, the residue
recrystallized from 1,4-dioxane.
was cooled to room temperature and decomposed in
ice cold water. The product that separated was fil-
tered, washed with water, dried and recrystallized from
ethanol.
2.3a 2,5,6-Trimethyl-3-[(2ꢁ-phenyl-5ꢁ-chloro-1H-indol-
3ꢁ-yl)methyleneamino]-thieno[2,3-d]pyrimidin-4(3H)-
one (4a): Yellow powder, Yield 0.29 g (65%), m. p.
185–186◦C; IR (KBr) ν cm−1 3301 (indole NH), 1648
(CO), 1598 (C=N); 1H NMR (500 MHz, DMSO-d6) δ
11.3 (s, 1H, indole NH), 9.1 (s, 1H, CH=N), 7.1–7.9
(m, 8H, ArH), 3.2 (s, 3H, 2-CH3), 2.8 (s, 3H, 6-CH3),
2.4 (s, 3H, 5-CH3); 13C NMR (125 M Hz, DMSO-d6):
δ 13.2, 14.3, 16.2, 114.2, 121.4, 122.5, 125.7, 126.6,
128.4, 129.0, 130.4, 130.8, 130.9, 133.2, 134.4, 134.6,
134.9, 142.1, 142.5, 143.8, 150.6, 172.8; EI-MS; m/z
446, 448; Anal. calcd. for C24H19N4OSCl: C 64.57; H,
4.26; N, 12.56. Found: C, 64.71; H, 4.41; N, 12.31.
2.4a 2,5,6-Trimethyl-3-[2-(2ꢁ-phenyl-5ꢁ-chloro-1H-indol-
3-yl)-4-oxothiazolidin-3-yl]thieno[2,3-d]pyrimidin-4(3H)-
one (5a): Yellow crystals, Yield 0.374 g (72%), m. p.
201–202◦C; IR (KBr) ν cm−1 3313 (indole NH), 1681
1
(CH2CO), 1645 (CO); H NMR (500 MHz, DMSO-
d6) δ 11.6 (s, 1H, indole NH), 10.0 (s, 1H, CH-N),
7.0–7.9 (m, 8H, ArH), 4.1 (s, 2H, CH2CO), 3.2 (s, 3H,
2-CH3), 2.7 (s, 3H, 6-CH3), 2.3 (s, 3H, 5-CH3); 13C
NMR (125 M Hz, DMSO-d6): δ 12.8, 13.7, 16.7, 35.7,
107.1, 113.8, 121.5, 122.6, 125.4, 126.4, 129.0, 129.3,
130.2, 130.5, 130.8, 133.1, 134.2, 134.5, 134.9, 143.5,
143.8, 149.9,. 168.7, 172.7; EI-MS; m/z 520, 522;
Anal. calcd. for C26H21N4O2S2Cl: C 60.00; H, 4.04; N,
10.77. Found: C, 60.21; H, 4.32; N, 10.52.
2.3b 2,5,6-Trimethyl-3-[(2ꢁ-phenyl-5ꢁ-methyl-1H-indol-
3ꢁ-yl)methyleneamino]-thieno[2,3-d]pyrimidin-4(3H)-
one (4b): Pale yellow powder, Yield 0.276 g (65%),
m. p. 162–163◦C; IR (KBr) ν cm−1 3305 (indole NH),
1646 (CO), 1595 (C=N); 1H NMR (500 MHz, DMSO-
d6) δ 11.4 (s, 1H, indole NH), 9.0 (s, 1H, CH=N),
7.0–7.9 (m, 8H, ArH), 3.3 (s, 3H, 2-CH3), 2.8 (s, 3H,
6-CH3), 2.5 (s, 3H, 5ꢁ-CH3), 2.3 (s, 3H, 5-CH3); 13C
NMR (125 M Hz, DMSO-d6): δ 13.3, 14.2, 16.6, 24.5,
114.3, 121.6, 122.8, 125.9, 126.9, 128.2, 129.1, 130.0,
130.5, 131.1, 133.4, 134.5, 134.9, 135.2, 142.3, 142.5,
143.5, 150.8, 172.3; Anal. calcd. for C25H22N4OS: C
70.42; H, 5.16; N, 13.14. Found: C, 70.55; H, 5.21; N,
13.05.
2.4b 2,5,6-Trimethyl-3-[2-(2ꢁ-phenyl-5ꢁmethyl-1H-indol-
3-yl)-4-oxothiazolidin-3-yl]thieno[2,3-d]pyrimidin-4(3H)-
one (5b): Pale yellow crystals, Yield 0.35 g (70%),
m. p. 191–192◦C; IR (KBr) ν cm−1 3308 (indole NH),
1685 (CH2CO), 1647 (CO); 1H NMR (500 MHz,
DMSO-d6) δ 11.5 (s, 1H, indole NH), 10.1 (s, 1H,
CH-N), 7.1–8.1 (m, 8H, ArH), 4.0 (s, 2H, CH2CO), 3.1
(s, 3H, 2-CH3), 2.6 (s, 3H, 6-CH3), 2.5 (s, 3H, 5ꢁ-CH3),
2.2 (s, 3H, 5-CH3); 13C NMR (125 M Hz, DMSO-d6):
δ 13.1, 14.1, 16.8, 24.3, 35.5, 107.3, 113.7, 121.4,
122.7, 125.4, 126.5, 129.1, 129.4, 130.2, 130.6, 130.7,
133.2, 134.1, 134.5, 134.7, 143.4, 143.7, 149.8, 168.5,
172.8; Anal. calcd. for C27H24N4O2S2: C 64.80; H,
4.80; N, 11.12. Found: C, 64.97; H, 4.57; N, 11.37.
2.3c 2,5,6-Trimethyl-3-[(2ꢁ-phenyl-5ꢁ-1H-indol-3ꢁyl)me-
thyleneamino]-thieno[2,3-d]pyrimidin-4(3H)-one (4c):
Pale yellow powder, Yield 0.26 g (63%), m. p. 179–
180◦C; IR (KBr) ν cm−1 3307 (indole NH), 1652 (CO),
2.4c 2,5,6-Trimethyl-3-[2-(2ꢁ-phenyl-1H-indol-3-yl)-
4-oxothiazolidin-3-yl]thieno[2,3-d]pyrimidin-4(3H)-
one (5c): Pale yellow powder, Yield 0.315 g (65%),
1
1599 (C=N); H NMR (500 MHz, DMSO-d6) δ 11.3
(s, 1H, indole NH), 9.1 (s, 1H, CH=N), 7.1–8.0 (m,
9H, ArH), 3.3 (s, 3H, 2-CH3), 2.7 (s, 3H, 6-CH3), 2.2

472
Anand Raghunath Saundane et al.
m. p. 186–187◦C; IR (KBr) ν cm−1 3310 (indole NH), 172.8; Anal. calcd. for C27H23N4O2SCl: C, 64.54; H,
1683 (CH2CO), 1649 (CO); 1H NMR (500 MHz, 4.58; N, 11.16. Found: C, 64.71; H, 4.43; N, 11.29.
DMSO-d6) δ 11.4 (s, 1H, indole NH), 10.0 (s, 1H,
CH-N), 7.0–8.0 (m, 9H, ArH), 4.1 (s, 2H, CH2CO), 3.2
(s, 3H, 2-CH3), 2.6 (s, 3H, 6-CH3), 2.3 (s, 3H, 5-CH3);
2.5c 2,5,6-Trimethyl-3-[3-chloro-2-(2ꢁ-phenyl-1H-indol-
3-yl)-4-oxoazetidin-1-yl]-thieno[2,3-d]pyrimidin-4(3H)-
one (6c): Brown powder, Yield 0.3 g (62%), m. p.
199–200◦C; IR (KBr) ν cm−1 3305 (indole NH), 1728
Anal. calcd. for C26H22N4O2S2: C 64.20; H, 4.53; N,
11.52. Found: C, 64.37; H, 4.67; N, 11.37.
1
(CHCO), 1649 (CO); H NMR (500 MHz, DMSO-
2.5 2,5,6-Trimethyl-3-[3-chloro-2-(2ꢁ-phenyl-5ꢁ-subs-
tituted 1H-indol-3ꢁ-yl)-4-oxoazetidin-1-yl]-thieno[2,
3-d]pyrimidin-4(3H)-ones (6a–c)
d6) δ 11.5 (s, 1H, indole NH), 10.0 (d, 1H, CH-N),
6.9–8.0 (m, 9H, ArH), 5.6 (d, 1H, CHCl), 3.3 (s, 3H,
2-CH3), 2.7 (s, 3H, 6-CH3), 2.2 (s, 3H, 5-CH3); Anal.
calcd. for C26H21N4O2SCl: C, 63.93; H, 4.30; N, 11.48.
Found: C, 63.87; H, 4.17; N, 11.61.
A mixture of compound 4 (0.001 mol) and triethyl
amine (0.001 mol) was dissolved in methanol (20 ml)
and cooled to 0◦C. To this well cooled solution,
chloroacetylchloride (0.001 mol) was added drop-wise
during 30 min with stirring at 0◦C. The reaction mixture
was further stirred for 1 h and refluxed for 12 h. The
triethyl amine hydrochloride salt formed was removed
by filtration. The filtrate was concentrated to its half
volume, cooled to room temperature and poured on
to crushed ice. The product was obtained was filtered,
washed with water and recrystallized from ethanol.
2.6 5,6-Dimethyl-3-[(2ꢁ-phenyl-5ꢁ-substituted 1H-indol-
3ꢁ-yl)methyleneamino]-thieno[2,3-d]pyrimidin-4(3H)-
ones (7 a–c)
A mixture of 3a–c (0.001) and triethyl orthoformate
(5 ml) in acetic anhydride (10 ml) was heated under
reflux for 7 h and then allowed to cool. The product
separated was collected and recrystallized from ethanol.
2.6a 5,6-Dimethyl-3-[(2ꢁ-phenyl-5ꢁ-chloro-1H-indol-
3ꢁ-yl)methyleneamino]-thieno[2,3-d]pyrimidin-4(3H)-
one (7a): Yellow powder, Yield 0.315 g (73%), m. p.
175–176◦C; IR (KBr) ν cm−1 3301 (indole NH), 1645
(CO), 1597 (C=N); 1H NMR (500 MHz, DMSO-d6) δ
11.3 (s, 1H, indole NH), 9.0 (s, 1H, CH=N), 8.5 (s,
1H, pyrimidin-H), 7.0–7.9 (m, 8H, ArH), 2.7 (s, 3H,
6-CH3), 2.3 (s, 3H, 5-CH3); 13C NMR (125 M Hz,
DMSO-d6): δ 13.4, 14.2, 114.0, 121.4, 122.0, 125.6,
126.2, 129.0, 129.2, 130.1, 130.6, 130.9, 133.1, 134.2,
134.6, 134.9, 142.1, 142.9, 143.8, 152.1, 172.9; EI-
MS; m/z 432, 434; Anal. calcd. for C23H17N4OSCl: C,
63.89; H, 3.93; N, 12.96. Found: C, 63.71; H, 4.10; N,
12.85.
2.5a 2,5,6-Trimethyl-3-[3-chloro-2-(2ꢁ-phenyl-5ꢁ-chloro-
1H-indol-3ꢁ-yl)-4-o xoazetidin-1-yl]-thieno[2,3-d]pyrimidin-
4(3H)-one (6a): Brown powder, Yield 0.36 g (69%),
m. p. 210–211◦C; IR (KBr) ν cm−1 3301 (indole
1
NH), 1720 (CHCO), 1645 (CO); H NMR (500 MHz,
DMSO-d6) δ 11.5 (s, 1H, indole NH), 10.0 (d, 1H,
CH-N), 6.9–7.8 (m, 8H, ArH), 5.6 (d, 1H, CHCl), 3.2
(s, 3H, 2-CH3), 2.7 (s, 3H, 6-CH3), 2.3 (s, 3H, 5-CH3);
13C NMR (125 M Hz, DMSO-d6): δ 13.2, 14.2, 16.7,
82.5, 106.3, 113.1, 113.7, 121.5, 122.5, 125.6, 126.1,
128.1, 129.1, 130.4, 130.5, 130.7, 134.1, 134.6, 134.9,
142.4, 143.8, 150.1, 160.6, 172.7; EI-MS; m/z 522,
524, 526; Anal. calcd. for C26H20N4O2SCl2: C, 59.77;
H, 3.83; N, 10.73. Found: C, 59.99; H, 3.71; N, 10.95.
2.5b 2,5,6-Trimethyl-3-[3-chloro-2-(2ꢁ-phenyl-5ꢁ-methyl- 2.6b 5,6-Dimethyl-3-[(2ꢁ-phenyl-5ꢁ-methyl-1H-indol-
1H-indol-3ꢁ-yl)-4-oxoazetidin-1-yl]-thieno[2,3-d]pyrimidin-
3ꢁ-yl)methyleneamino]-thieno[2,3-d]pyrimidin-4(3H)-
4(3H)-one (6b): Brown powder, Yield 0.342 g (68%), one (7b): Yellow powder, Yield 0.288 g (70%), m. p.
m. p. 214–215◦C; IR (KBr) ν cm−1 3309 (indole 169–171◦C; IR (KBr) ν cm−1 3305 (indole NH), 1645
1
1
NH), 1725 (CHCO), 1653 (CO); H NMR (500 MHz, (CO), 1594 (C=N); H NMR (500 MHz, DMSO-d6)
DMSO-d6) δ 11.4 (s, 1H, indole NH), 10.1 (d, 1H, δ 11.4 (s, 1H, indole NH), 9.1 (s, 1H, CH=N), 8.6
CH-N), 7.0–7.9 (m, 8H, ArH), 5.7 (d, 1H, CHCl), 3.3 (s, 1H, pyrimidin-H), 7.1–8.0 (m, 8H, ArH), 2.8 (s,
(s, 3H, 2-CH3), 2.7 (s, 3H, 6-CH3), 2.4 (s, 3H, 5ꢁ-CH3), 3H, 6-CH3), 2.4 (s, 3H, 5ꢁ-CH3), 2.2 (s, 3H, 5-CH3);
2.2 (s, 3H, 5-CH3); 13C NMR (125 M Hz, DMSO-d6): 13C NMR (125 M Hz, DMSO-d6): δ 13.5, 14.1, 24.3,
δ 13.1, 14.5, 16.8, 24.8, 82.3, 105.2, 106.2, 113.2, 114.2, 121.3, 122.5, 125.8, 126.3, 129.1, 129.4, 130.3,
113.8, 121.6, 122.4, 125.5, 126.3, 128.2, 129.1, 130.5, 130.8, 131.2, 133.5, 134.4, 134.7, 134.8, 142.3, 142.6,
130.6,130.8, 134.0, 134.5, 134.8, 142.4, 143.5, 160.5, 143.6, 152.4, 172.6; Anal. calcd. for C24H20N4OS: C,

Synthesis, antioxidant and antimicrobial evaluation of thiazolidinone, azetidinone encompassing
473
69.90; H, 4.85; N, 13.59. Found: C, 69.73; H, 4.98; N, 2.7c 5,6-Dimethyl-3-[2-(2ꢁ-phenyl-1H-indol-3-yl)-4-
13.67.
oxothiazolidin-3-yl]thieno[2,3-d]pyrimidin-4(3H)-one
(8c): Pale yellow powder, Yield 0.292 (62%), m. p.
189–190◦C; IR (KBr) ν cm−1 3307 (indole NH), 1707
2.6c 5,6-Dimethyl-3-[(2ꢁ-phenyl-5ꢁ-1H-indol-3ꢁ-yl)me-
thyleneamino]-thieno[2,3-d]pyrimidin-4(3H)-one (7c):
Pale yellow powder, Yield 0.286 (72%), m. p. 158–
159◦C; IR (KBr) ν cm−1 3307 (indole NH), 1653
1
(CH2CO), 1651 (CO); H NMR (500 MHz, DMSO-
d6) δ 11.5 (s, 1H, indole NH), 10.1 (s, 1H, CH-N),
8.5 (s, 1H, pyrimidin-H), 7.1–8.1 (m, 9H, ArH), 4.2 (s,
2H, CH2CO), 2.9 (s, 3H, 6-CH3), 2.3 (s, 3H, 5-CH3);
Anal. calcd. for C25H20N4O2S2: C, 63.56; H, 4.24; N,
11.86. Found: C, 63.29; H, 4.37; N, 11.69.
1
(CO), 1599 (C=N); H NMR (500 MHz, DMSO-
d6) δ 11.3 (s, 1H, indole NH), 9.0 (s, 1H, CH=N),
8.5 (s, 1H, pyrimidin-H), 7.1–8.1 (m, 9H, ArH), 2.7
(s, 3H, 6-CH3), 2.2 (s, 3H, 5-CH3); Anal. calcd. for
C23H18N4OS: C, 69.35; H, 4.52; N, 14.07. Found: C,
69.60; H, 4.69; N, 14.20.
2.8 5,6-Dimethyl-3-(3-chloro-2-(2ꢁ-phenyl-5ꢁ-substi-
tuted 1H-indol-3-yl)-4-oxoazetidin-1-yl)-
thieno[2,3-d]pyrimidin-4(3H)-ones (9 a–c)
2.7 5,6-Dimethyl-3-[2-(2ꢁ-phenyl-5ꢁ-substituted 1H-indol-
3ꢁ-yl)-4-oxothiazolidin-3-yl]thieno[2,3-d]pyrimidin-4(3H)-
ones (8 a–c)
These compounds were synthesized by following the
procedure reported for compounds 6 a–c.
2.8a 5,6-Dimethyl-3-[3-chloro-2-(2ꢁ-phenyl-5ꢁ-chloro-
1H-indol-3ꢁ-yl)-4-oxoazetidin-1-yl]-thieno[2,3-d]pyrimidin-
4(3H)-one (9a): Yellow flakes, Yield 0.283 g (59%),
m. p. 231–232◦C; IR (KBr) ν cm−1 3301 (indole
These compounds were synthesized following the pro-
cedure given for compounds 5 a–c.
2.7a 5,6-Dimethyl-3-[2-(2ꢁ-phenyl-5ꢁ-chloro-1H-indol-
3-yl)-4-oxothiazolidin-3-yl]thieno[2,3-d]pyrimidin-
4(3H)-one (8a): Pale yellow flakes, Yield 0.330 g
(72%), m. p. 215–216◦C; IR (KBr) ν cm−1 3301 (indole
NH), 1701 (CH2CO), 1645 (CO); 1H NMR (500 MHz,
DMSO-d6) δ 11.5 (s, 1H, indole NH), 10.0 (s, 1H,
CH-N), 8.7 (s, 1H, pyrimidin-H), 7.1–8.0 (m, 8H,
ArH), 4.2 (s, 2H, CH2CO), 2.7 (s, 3H, 6-CH3), 2.3 (s,
3H, 5-CH3); 13C NMR (125 M Hz, DMSO-d6): δ 13.4,
14.3, 35.8, 107.1, 113.9, 121.6, 122.5, 125.6, 126.3,
129.0, 129.3, 130.2, 130.5, 130.9, 133.0, 134.3, 134.6,
134.8, 142.3, 143.6, 152.3. 168.8, 172.8; EI-MS; m/z
506, 508; Anal. calcd. for C25H19N4O2S2Cl: C, 59.29;
H, 3.74; N, 11.07. Found: C, 59.42; H, 3.51; N, 11.29.
1
NH), 1735 (CHCO), 1645 (CO); H NMR (500 MHz,
DMSO-d6) δ 11.5 (s, 1H, indole NH), 10.0 (d, 1H, CH-
N), 8.6 (s, 1H, pyrimidine-H), 6.9–7.8 (m, 8H, ArH),
5.5 (d, 1H, CHCl), 2.7 (s, 3H, 6-CH3), 2.2 (s, 3H, 5-
CH3); 13C NMR (500 M Hz, DMSO-d6): δ 12.9, 14.1,
82.4, 106.2, 113.8, 121.4, 122.4, 125.5, 126.2, 128.2,
129.2, 130.2, 130.4, 130.9, 133.2, 134.2, 134.7, 134.9,
142.4, 143.7, 152.4, 160.6, 172.8; EI-MS; m/z 508,
510, 512; Anal. calcd. for C25H18N4O2SCl2: C, 59.05;
H, 3.54; N, 11.02. Found: C, 59.21; H, 3.69; N, 11.20.
2.8b 5,6-Dimethyl-3-[3-chloro-2-(2ꢁ-phenyl-5ꢁ-methyl-
1H-indol-3ꢁ-yl)-4-oxoazetidin-1-yl]-thieno[2,3-d]pyrimidin-
4(3H)-one (9b): Yellow powder, Yield 0.282 (59%),
m. p. 223–224◦C; IR (KBr) ν cm−1 3315 (indole
2.7b 5,6-Dimethyl-3-[2-(2ꢁ-phenyl-5ꢁ-methyl-1H-indol-
3-yl)-4-oxothiazolidin-3-yl]thieno[2,3-d]pyrimidin-
4(3H)-one (8b): Yellow flakes, Yield 0.305 g (65%),
m. p. 205–206◦C; IR (KBr) ν cm−1 3310 (indole NH),
1705 (CH2CO), 1649 (CO); 1H NMR (500 MHz,
DMSO-d6) δ 11.4 (s, 1H, indole NH), 10.1 (s,
1H, CH-N), 8.6 (s, 1H, pyrimidin-H), 7.2–8.1 (m,
8H, ArH), 4.3 (s, 2H, CH2CO), 2.8 (s, 3H, 6-CH3),
2.4 (s, 3H, 5ꢁ-CH3), 2.3 (s, 3H, 5-CH3); 13C NMR
(125 M Hz, DMSO-d6): δ 13.3, 14.2, 24.3, 35.8, 107.1,
113.7, 121.4, 122.7, 125.8, 126.5, 129.1, 129.4, 130.4,
130.7,130.9, 133.2, 134.2, 134.6, 134.8, 142.6, 143.8,
152.5, 168.8, 172.8; Anal. calcd. for C26H22N4O2S2: C,
64.20; H, 4.53; N, 11.52. Found: C, 64.35; H, 4.32; N,
11.67.
1
NH), 1730 (CHCO), 1654 (CO); H NMR (500 MHz,
DMSO-d6) δ 11.4 (s, 1H, indole NH), 10.1 (d, 1H,
CH-N), 8.5 (s, 1H, pyrimidine-H), 6.8–7.8 (m, 8H,
ArH), 5.6 (d, 1H, CHCl), 2.7 (s, 3H, 6-CH3), 2.5 (s,
3H, 5ꢁ-CH3), 2.3 (s, 3H, 5-CH3); 13C NMR (500 M
Hz, DMSO-d6): δ 13.1, 14.2, 24.5, 82.5, 106.2, 113.7,
121.5, 122.5, 125.7, 126.3, 128.3, 129.1, 130.1, 130.6,
130.7, 133.4, 134.3, 134.8, 134.9, 142.5, 143.9, 152.6,
160.7, 172.7; Anal. calcd. for C26H21N4O2SCl: C,
63.93; H, 4.30; N, 11.48. Found: C, 63.78; H, 4.51; N,
11.29.
2.8c 5,6-Dimethyl-3-[3-chloro-2-(2ꢁ-phenyl-5ꢁ-1H-indol-3-
yl)-4-oxoazetidin-1-yl]-thieno[2,3-d]pyrimidin-4(3H)-one
(9c): Yellow powder, Yield 0.26 g (55%), m. p.

474
Anand Raghunath Saundane et al.
1
198–199◦C; IR (KBr) ν cm−1 3313 (indole NH), 1727 of compound (3) was confirmed by its IR, H NMR,
1
(CHCO), 1653 (CO); H NMR (500 MHz, DMSO- 13C NMR and mass spectrum studies. In IR spectrum of
d6) δ 11.3 (s, 1H, indole NH), 10.2 (d, 1H, CH-N), 8.5 compound (3a), various bands appeared at 3404, 3301,
(s, 1H, pyrimidine-H), 6.8–7.9 (m, 9H, ArH), 5.7 (d, 3170, 1645 and 1597 cm−1 were due to NH2, indole
1H, CHCl), 2.8 (s, 3H, 6-CH3), 2.3 (s, 3H, 5-CH3); NH, NH, C=O and C=N functions, respectively. In
Anal. calcd. for C25H19N4O2SCl: C, 63.29; H, 4.01; N, 1H NMR spectrum of compound (3a) exhibited var-
11.81. Found: C, 63.52; H, 4.22; N, 11.67.
ious signals at δ 11.5 (s, 1H, indole NH), 9.9 (s, 1H,
NH), 8.9 (s, 1H, CH=N), 7.1–8.0 (m, 10H, 8-ArH and
NH2), 2.7 (s, 3H, 5-CH3) and 2.3 (s, 3H, 4-CH3). The
two distinctive signals at δ 142.6 and 171.2 due to the
CH=N and amide carbonyl in its 13C NMR confirmed
the formation of compound 3a. Where as in mass
3. Result and discussion
In the present investigation, we have synthesized spectrum, compound 3a exhibited isotopic molecular
fused thienopyrimidines linked to position-3 of indole ion peaks at 422 and 424 confirms the formation of
nucleus. The synthetic route to achieve the target 3a. Compound 3 on cyclization with acetic anhydride
compounds was given in the scheme 1. First, 2-amino- yielded thienopyrimidine derivatives (4). Structural
1
4,5-dimethyl thiophene-3-charbohydrazide (2) was confirmation of compound 4a was done using IR, H
prepared by following literature method.45 This on NMR, 13C NMR and mass spectra. The IR spectrum
reaction with hydrazine hydrate gave compound (2). showed characteristic absorption bands at 3301, 1648
Compound (2) on condensation with 2.5-disubstituted and 1598 cm−1 due to indole NH, C=O and C=N
1H-indole-3-carboxaldehydes46 (1) afforded 2-amino- functions respectively and NH2 and NH functions were
1
Nꢁ-{3-(2ꢁ-phenyl-5ꢁ-substituted 1H-indol-3ꢁ-yl)methylene}- disappeared. In H NMR spectrum, various signals
4,5-dimethylthieno-3-carbohydrazides (3). Formation resonated at δ 11.3 (s, 1H, indole NH), 9.1 (s, 1H,
CHO
R
H2NHNOC
H2N
CH3
CH3
N
H
S
1 a-c
2
O
CH3
CH3
CH=NNHC
R
H2N
S
N
H
3 a-c
Ac2O
TEOF/Ac2O
O
H
C
O
N
CH3
CH3
H
C
N
CH3
CH3
R
S
N
N
R
N
H3C
N
S
N
S
N
H
H
7 a-c
4 a-c
O
O
N
O
N
S
O
CH3
CH3
CH3
CH3
N
R
N
R
N
HSCH2COOH
HSCH2COOH
H3C
S
N
S
N
N
H
H
ClCH2COCl
Et3N
ClCH2COCl
Et3N
8 a-c
5 a-c
Cl
O
Cl
O
O
O
N
N
CH3
CH3
R
N
N
R
N
N
S
CH3
H3C
N
S
CH3
N
H
H
9 a-c
Where
R=
6 a-c
a
Cl
b
CH3
c
H
Scheme 1. Synthesis of compounds 5a-c, 8a-c and 5a-c, 9a-c from 3a-c.

Synthesis, antioxidant and antimicrobial evaluation of thiazolidinone, azetidinone encompassing
475
100
CH=N), 7.1–7.9 (m, 8H, ArH), 3.2 (s, 3H, CH3), 2.8
(s, 3H, 6-CH3) and 2.4 (s, 3H, 5-CH3). The new peaks
in its 13C NMR at δ16.2 and 150.6 appeared due to the
methyl group at 2-position of pyrimidothiophene C2
of pyrimidine system. In mass spectrum, 4a exhibited
isotopic molecular ion peaks at 446 and 448 confirms
the formation of 4a. Cyclization of compound (4) with
thioglycolic acid afforded thiazolidin-4-one deriva-
tives (5). 5a Exhibited various absorption bands in
its IR spectrum at 3313, 1681 and 1645 cm−1 due to
indole NH, CH2CO and C=O functions, respectively.
90
80
70
60
50
40
30
20
10
0
3a
3b
3c
4a
4b
4c
BHA
TBHQ
1
In H NMR spectrum, various signals at δ 11.6 (s,
0
20
40
60
80
100
1H, indole NH), 10.0 (s, 1H, CH-N), 7.0–7.9 (m. 8H,
ArH), 4.1 (s, 2H, CH2CO), 3.2 (s, 3H, 2-CH3), 2.7 (s,
3H, 6-CH3) and 2.3 (s, 3H, 5-CH3) were appeared.
13CNMR spectrum, the new signals at δ 35.7 and 107.1
were resonated due to the CH and CH2 carbon of
thiazolidine system. The mass spectrum of compound
5a exhibited isotopic molecular ion peaks at 520 and
522 confirms the formation of 5a. Also, compounds
(4) on treatment with chloroacetylchloride in triethy-
lamine gave azetidin-2-ones (6). Compound 6a in its
IR spectrum showed characteristic absorption bands at
3301, 1720 and 1645 due to indole NH, CHCO and
C=O functions, respectively. In its 1H NMR spectrum,
6a showed the absence of NH2 and NH signals and
presence of signals at 11.5 (s, 1H, indole NH), 10.0 (d,
1H, CH-N), 6.9–7.8 (m, 8H, ArH), 3.2 (s, 3H, 2-CH3),
2.7 (s, 3H, 6-CH3), 2.3 (s, 3H, 5-CH3) and appearance
of new doublet signal at 5.6 (d, 1H, CH–Cl) confirms
the presence of lactum ring. Further, the signals at δ
82.5 and 160.6 corresponding to the CH and CH–Cl of
azetidinone moiety. Compound 6a exhibited isotopic
molecular ion peaks at 522, 524 and 526 confirms the
formation of lacum ring.
Concentration (µg/ml)
Figure 1. Reducing power of compounds 3 and 4.
in DMSO (1 ml) were mixed with phosphate buffer
(2.5 ml, 0.2 mol, pH=6.6) and potassium ferricyanide
(2.5 ml, 1%). The mixture was incubated at 50◦C for
20 min. after which a portion (2.5 ml) of trichloroacetic
acid (10%) was added to the mixture, which was
then centrifuged for 10 min. at 1000 × g. The upper
layer of solution (2.5 ml) was mixed with distilled
water (2.5 ml) and FeCl3 (0.5 ml, 0.1%), and then the
absorbance at 700 nm was measured in a spectropho-
tometer. BHA, TBHQ and ascorbic acid (A. A) were
used as standards.
4.2 Radical scavenging activity (RSA) assay
The free radical scavenging activity of 3–9 was
carried out in the presence of the stable free
radical DPPH following Hatano’s method48 using
On the other hand, compound 3 ion reaction with
triethyhlorthoformate in actic anhydride gave thienopy-
rimidines (7). Compound (7) on reaction with
thioglycolic acid afforded the indole derivative of
thiazolidin-4-ones (8). Further, compound (7) on
cyclocondensation with chloacetylchloride, produced
azetidin-2-ones (9). Structure of compounds 7, 8 and
9 were confirmed by their spectral studies (see experi-
mental section).
100
90
80
70
60
50
40
30
20
10
0
5a
5b
5c
6a
6b
6c
BHA
TBHQ
4. Biological activities
4.1 Reducing power assay
0
20
40
60
80
100
The reducing power of the synthesized compounds was
determined according to the method of Oyaizu.47 Dif-
ferent concentrations of the samples (25–100 μg/ml)
Concentration (µg/ml)
Figure 2. Reducing power of compounds 5 and 6.

476
Anand Raghunath Saundane et al.
100
1.4
1.2
90
80
70
60
50
40
30
20
10
0
1.0
7a
7b
7c
8a
8b
8c
9a
9b
5a
5b
5c
6a
6b
6c
A. A
BHA
TBHQ
0.8
0.6
0.4
0.2
0.0
9c
BHA
TBHQ
0
20
40
60
80
100
0
20
40
60
80
100
Concentration (µg/mL)
Concentration (µg/ml)
Figure 5. DPPH Radical scavenging activity of com-
pounds 5 and 6.
Figure 3. Reducing power of compounds 7, 8 and 9.
2-tert-butyl-4-methoxyphenol (butylated hydroxyl
anisole, BHA), 2-(1,1-dimethylethyl)-1,4-benzenediol
(2-tert. butyl hydroquinone, TBHQ) and ascorbic acid
as standards. The radical scavenging activity (RSA)
for methanolic solutions of compounds 3–9 at concen-
trations 25, 50, 75 and 100 μg/ml containing freshly
prepared DPPH solution (0.004% w/v) was carried out
and compared with those of standards BHA and TBHQ.
All the test analyses were performed on three replicates
and results are averaged. The results in percentage are
expressed as the ratio of absorption decrease of DPPH
in the presence of test compounds and absorption of
DPPH in the absence of test compounds at 517 nm
using ELICO SL 171 Mini Spec spectrophotometer.
The percentage scavenging activity of the DPPH free
radical was measured using the following equation
%DPPH radical scavenging
Absorbance of control−Absorbance of test sample
=
Absorbance of control
× 100.
Antioxidant activity of these compounds was inves-
tigated by measuring the reducing power and radi-
cal scavenging effect of DPPH radicals. In reducing
power assay, the presence of reducer (i.e., antioxi-
dant) causes the reduction of Fe+3/ferricyanide com-
plex to ferrous form. The reducing power of the test
1.5
1.4
1.3
1.2
1.1
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
1.5
1.4
1.3
1.2
1.1
7a
7b
7c
8a
8b
8c
9a
9b
9c
1.0
0.9
3a
3b
3c
4a
4b
4c
A. A
BHA
TBHQ
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
A. A
BHA
TBHQ
0
20
40
60
80
100
0
20
40
60
80
100
Concentration (µg/mL)
Concentration (µg/mL)
Figure 4. DPPH Radical scavenging activity of com- Figure 6. DPPH Radical scavenging activity of com-
pounds 3 and 4. pounds 7, 8 and 9.

Synthesis, antioxidant and antimicrobial evaluation of thiazolidinone, azetidinone encompassing
477
compounds increases with increase in concentration. system) are available. One of these hydrogens could be
Compounds 3–9 exhibited very low absorption hence, donated to the DPPH free radical to form the stable
the compounds were less active compared to standards DPPH molecule. The radical formed from compound
used (figures 1–3). In case of radical scavenging activ- 5 could be well-stabilized by resonance as shown in
ity, compounds 5 and 7 showed good percentage of schemes 2 and 3. In case of compound 7, the hydro-
inhibition (figures 4–6).
gen(s) of azomethine and methyl group at position-6 of
The probable mode of action of compounds 5 and thienopyrimidine are much more acidic than the hydro-
7 was illustrated in schemes 2, 3 and 4. In case gen of the indole NH. Hence, these could be easily
of compound 5, two labile hydrogen (hydrogen of donated to DPPH free radical and convert itself into the
indole NH and other at position-2 in 1,3-thiazolidinone stable free radical, which could be well-stabilized by
O
O
N
S
NO2
NO2
CH3
CH3
N
R
N
H
N
N
O2N
S
H3C
N
H
Compound 5
DPPH radical
O
N
O
S
NO2
CH3
CH3
N
H
R
N
NH
N
O2N
S
H3C
N
NO2
DPPH-H
O
O
N
S
CH3
CH3
N
R
N
H
etc.
S
H3C
N
O
O
N
S
CH3
N
R
N
H
S
CH3
H3C
N
Scheme 2. DPPH radical scavenging activity: Probable mode of action of compound 5
and stabilization of free radical formed after donating hydrogen of indole NH.

478
Anand Raghunath Saundane et al.
O
O
S
NO2
NO2
CH3
N
R
N
N
N
O2N
H3C
N
S
CH3
N
H
Compound 5
DPPH radical
O
O
S
NO2
CH3
CH3
N
R
N
NH
N
O2N
H3C
N
S
N
H
NO2
DPPH-H
O
S
O
N
CH3
CH3
N
R
N
etc.
H3C
S
N
H
O
O
S
CH3
N
R
N
H3C
N
S
CH2
N
H
Scheme 3. DPPH radical scavenging activity: Probable mode of action of compound 5
and stabilization of free radical formed after donating hydrogen from thiazolidin-4-one
system.
resonance as shown in scheme 4. Thus, compounds 5 aeroginosa (Gram negative bacteria), Staphylococcus
and 7 could act as good hydrogen donors and antioxi-
dant as compared to rest of the compounds tested. The
same principle holds good for the reducing power assay
of compounds 5 and 7.
aureus and Klebsiella pneumoniae (gram negative
bacteria), Aspergillus oryzae, Aspergillus terrus and
Aspergillus niger (fungi). An aliquot 0.1 ml of each bac-
terial strain was on nutrient agar while 0.1 ml of the
fungal spore suspension was spread on potato dextrose
agar (PDA). An agar-well diffusion test was performed
in each case. In these tests, 6 mm wells were pro-
duced by using a sterile cork borer and each well was
then inoculated with 100 μL of each key substance in
4.3 Antimicrobial assay
The antimicrobial activities49 of the compounds pre-
pared in this effort were evaluated using Pseudomonas

Synthesis, antioxidant and antimicrobial evaluation of thiazolidinone, azetidinone encompassing
479
O
NO2
CH3
N
HC
R
N
N
N
O2N
N
S
CH3
N
H
NO2
Compound 7
DPPH radical
O
N
CH3
NO2
N
C
R
N
NH
N
O2N
S
CH3
N
H
NO2
DPPH-H
O
CH3
N
C
R
N
etc.
N
S
CH3
N
H
O
CH3
N
HC
R
N
N
S
CH2
N
H
Scheme 4. DPPH radical scavenging activity: Probable mode of action of compound
7 and stabilization of free radical formed after donating hydrogen radical.
DMF, resulting in a final concentration of 1000 μg/ml. produced maximum zone of inhibition against A.
Nutrient agar plates were incubated at 37◦C for Oryzae. Compound 9a exhibited maximum inhibitory
24 h while the PDA plates incubated at 25◦C for growth against A. Terrus and compounds 5a and 6a
72 h. The zone of inhibition around the well was shown maximum zone of inhibition against A. Nizer
determined. Gentamycin and flucanozole were used (table 1).
as the reference antibacterial and antifungal agents,
respectively.
These results suggest that, compounds having chloro
substituent were much more capable of inhibiting the
In antimicrobial activity, compounds 3a, 5a, 6a and growth of organism compared to other compounds. This
9a showed good zone of inhibition against S. Aureus, may be due to the electronegative nature of the chlo-
compounds 3a, 6a and 9a exhibited maximum zone rine atom in the position-5 of indole nucleus in addi-
of inhibition against P. Knemonia. Where as in case tion to the different heterocyclic systems present in the
of antifungal activity, compounds 5a, 6a, 9a and 9b individual compounds.

480
Anand Raghunath Saundane et al.
Table 1. Antimicrobial activities of synthesized compounds (3–9).
Comp. No.
Antibacterial activity (zone of inhibition in mm)
Antifungal activity (zone of inhibition in mm)
S. aureus
P. aeruginosa
K. pneumonia
A. oryzae
A. terrus
A. nizer
3a
3b
3c
4a
4b
4c
5a
5b
5c
6a
6b
6c
7a
7b
7c
8a
14
13
12
11
10
10
14
12
13
14
13
12
12
09
08
13
12
11
14
13
12
15
–
10
09
13
12
09
08
12
10
09
13
12
11
10
10
07
12
10
10
13
09
12
16
–
14
10
09
12
10
09
13
11
10
14
13
11
09
08
08
12
13
11
14
10
10
15
–
12
09
08
08
10
11
13
12
09
13
09
12
10
09
07
10
12
11
13
13
12
–
12
10
09
07
10
12
11
12
10
12
10
10
11
12
10
10
09
10
13
11
12
–
10
11
12
10
10
09
13
10
11
13
10
12
13
09
10
10
11
11
12
12
10
–
8b
8c
9a
9b
9c
Gentamycin
Flucanozole
14
15
14
5. Conclusion
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Acknowledgements
The authors are thankful to the Chairman, Department
of Chemistry, Gulbarga University, Gulbarga, for pro-
viding laboratory facilities. We are also thankful to the
Director, Indian Institute of Technology, Chennai for
providing spectral data.
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