Synthesis of some new mono, bis-indolo[1,2-c]quinazolines: Evaluation of their antimicrobial studies

Article abstract of DOI:10.1590/S0103-50532010000500018

A convenient three-step strategy is proposed for the synthesis of mono and bis-indolo[1, 2-c] quinazolines from 2-(2-aminophenyl)indole and various aryl aldehydes. The newly synthesized compounds were characterized by elemental analysis, IR, ¹H NMR, ¹³C NMR, and mass spectroscopic investigation. All the derivatives were screened for antibacterial (S. aureus, B. subtilis, S. pyogenes, S. typhimurium, E. coli, K. pneumonia) and antifungal (A. niger, C. albicans, T. viridae) activities by cup plate method. Among the compounds tested, mono- indolo[1, 2-c] quinazolines (15-18) exhibited good antibacterial activities while 15 and 18 also showed notable antifungal activity. Especially, 19 and 20 exhibited stronger antibacterial as well as antifungal activity against all tested strains.

Full text of DOI:10.1590/S0103-50532010000500018

J. Braz. Chem. Soc., Vol. 21, No. 5, 897-904, 2010.
Printed in Brazil - ©2010 Sociedade Brasileira de Química
0103 - 5053 $6.00+0.00
Synthesis of Some New Mono, Bis-Indolo[1, 2-c]quinazolines:
Evaluation of their Antimicrobial Studies
Rondla Rohini,a,c P. Muralidhar Reddy,a,b Kanne Shanker,a
Anren Hu*,c and Vadde Ravinder*,a
aDepartment of Chemistry, Kakatiya University, Warangal-506 009, A.P, India
bDepartment of Chemistry, National Dong Hwa University, Hualien, Taiwan
cDepartment of Laboratory Medicine and Biotechnology, Tzu Chi University, Hualien, Taiwan
Uma estratégia conveniente em três etapas é proposta para a síntese de mono e bis-indolo[1,2-c]
quinazolinas, a partir de 2-(2-aminofenil)indol e aril aldeídos. Os novos compostos sintetizados
foram caracterizados por análise elementar, IV, 1H RMN, 13C RMN, e espectrometria de massa.
Todos os derivados foram testados para avaliação das suas atividades antibacterial (S. aureus,
B. subtilis, S. pyogenes, S. typhimurium, E. coli, K. pneumonia) e antifúngica (A. niger, C. albicans,
T. viridae) usando o método cup plate. Dentre os compostos testados, as mono- indolo[1,2-c]
quinazolinas (15-18) exibiram boas atividades antibacteriais, enquanto 15 e 18 também mostraram
notável atividade antifúngica. Especialmente, 19 e 20 exibiram forte atividade antibacteriana e
antifúngica contra todas as cepas testadas.
A convenient three-step strategy is proposed for the synthesis of mono and bis-indolo[1,2-c]
quinazolines from 2-(2-aminophenyl)indole and various aryl aldehydes. The newly synthesized
1
compounds were characterized by elemental analysis, IR, H NMR, 13C NMR, and mass
spectroscopic investigation.All the derivatives were screened for antibacterial (S. aureus, B. subtilis,
S. pyogenes, S. typhimurium, E. coli, K. pneumonia) and antifungal (A. niger, C. albicans, T. viridae)
activities by cup plate method. Among the compounds tested, mono- indolo[1,2-c] quinazolines
(15-18) exhibited good antibacterial activities while 15 and 18 also showed notable antifungal
activity. Especially, 19 and 20 exhibited stronger antibacterial as well as antifungal activity against
all tested strains.
Keywords: indolo[1,2-c]quinazolines, synthesis, antibacterial activity, antifungal activity
Introduction
The introduction of an additional substituent on the indole
nuclei has been increasing attention in the expectation that
such changes could potentially affect the interaction of
the molecules with biological targets. Fused cyclic indole
derivatives, such as indolocarbazoles,16,17 indolo[2,3-b]
quinolines,18,19 indolo[l,2-c] quinazolines,20,21 bis-indoles22,23
and many others, have also interesting pharmacological
properties. Moreover, indoles and their cyclic derivatives
constitute an important class of compounds for new drug
development in order to discover an effective compound
against multi-drug-resistant microbial infections. Recently,
Gurkok et al.24 synthesized a series of indole-3-aldehyde
and 5-bromoindole-3-aldehyde hydrazide and hydrazones
and evaluated for their in vitro antimicrobial activities
using the 2-fold serial dilution technique. Very recently,
a series of 2-o-arylidineaminophenylindoles and their
The indole is a crucial heterocyclic skeleton often
associated with pharmacological properties.1,2 It is a
fundamental constituent of a number of natural and
synthetic products with biological activity.3,4 Due to
the structural similarity of indole nuclei with some
naturally occurring compounds such as serotonin,
tryptamine, hinckdentine A, they can easily interact with
biomolecules of the living systems.5,6 Heterocycles bearing
an indole moiety are reported to show a broad spectrum
of pharmacological and medicinal properties such as
anti-inflammatory,7,8 anticonvulsant,9 antimicrobial,10,11
antimalarial,12,13 anticancer14,15 and many other activities.
*e-mail: anren@mail.tcu.edu.tw; ravichemku@rediffmail.com

898
Synthesis of Some New Mono, Bis-Indolo[1, 2-c]quinazolines
J. Braz. Chem. Soc.
cyclic derivatives were synthesized and evaluated for
their antibacterial as well as antifungal activities.25 These
observations have encouraged us to synthesize some new
products containing the indole moiety hoping to obtain
new compounds with potential biological activity. At
last, we have succeeded in the preparation of several
new indolo[1,2-c]quinazolines derivatives, which are
structurally related to terrestrial or marine alkaloids (e.g.
hinckdentine A). In addition all the newly synthesized
quinazolines were screened for their in vitro antimicrobial
activity.
reported the synthesis of indolo[1,2-c] quinazolines via
iminophosphoranes.
In the present investigation, a convenient three-step
strategy has been developed for the synthesis of mono and
bis-indolo[1,2-c]quinazolines using 2-(2-aminophenyl)
indole (A) as a key compound (Scheme 1). The required
starting material A was prepared by the Fischer indole
synthesis from phenylhydrazine hydrochloride and
2-amino acetophenone using a mixture of methane sulfonic
acid and phosphorus pentoxide.5 The condensation of
2-(2-aminophenyl)indole (A) with different aromatic
aldehydes (Ar-CHO/CHO-Ar-CHO), yielded mono
and bis-2-(2-arylideneaminophenyl)indoles, which on
treatment with powdered KMnO4 in acetone furnished
mono and bis-indolo[1,2-c]quinazolines in good yields.
The structural assignments to the new compounds were
based on their elemental analysis and spectral (IR, 1H NMR,
13C NMR and mass) data.
The IR spectrum of 2-(2-aminophenyl)indole (A)
exhibited an absorption band at 3380-3440 cm-1 due to the
amino phenyl ring. All 2-(2-arylideneaminophenyl)indole
intermediates (1-10) and precursor A exhibit characteristic
IR absorption bands in the regions 3330-3400cm-1 and
1540-1560cm-1 indicative of –NH stretching and bending
vibrations of indole ring, respectively.30 The formation
of intermediate azomethines (1-10) was identified by
Results and Discussion
Chemistry
The indolo[1,2-c]quinazoline ring system was first
prepared in 1956 by Kiang et al.,26 and Cava and Billimoria27
have reviewed the chemistry of indoloquinazolines, which
are uncommon in nature. Moreover, they have published an
interesting approach to the synthesis of hinckdentineA and
other indolo[1,2-c]quinazoline derivatives.5 Frere et al.28
have developed a successful microwave assisted strategy
for the synthesis of novel 6-substituted indolo[1,2-c]
quinazolines by the condensation of 2-(2-aminophenyl)
indole with 2-cyanobenzothiazoles. Molina et al.29
NH2
N
N
NHNH2
Ar
O
6-Arylindolo[1,2-c]quinazolines
(11-18)
1.EtOH / AcOH
2. CH3SO3H / P2O5
KMnO4
reflux, 40-56 °C
Ar
N
NH
N
OHC-Ar-CHO
Ar-CHO
ethanol
ethanol
Ar
N
H
1:1
N
2:1
N
N
H
H2N
H
2-(o-arylidineaminophenyl)indoles
2-(o-aminophenyl)indole (A)
(1-8)
Bis-2-(o-arylidineaminophenyl)indoles
(9-10)
KMnO4
reflux, 50-60 °C
Ar- :
9,19 = 2,5-di thienyl
10,20 = 2,6-di pyridyl
-Ar- :
1,11 = Phenyl
5,15 = 2-pyridyl
2,12 = 2-naphthyl
6,16 = 1H-2-pyrrolyl
7,17 = 2-furyl
N
N
3,13 = 6-methoxy-2-naphthyl
Ar
N
4,14 = 1-nitro-2-naphthyl
8.18 = 2-thienyl
N
Bis-6-Arylindolo[1,2-c]quinazolines
(19-20)
Scheme 1. Synthesis of 6-arylindolo[1,2-c]quinazolines (11-20).

Vol. 21, No. 5, 2010
Rohini et al.
899
disappearance of peaks at 1680-1695 cm-1 for –CHO and
3380-3440 cm-1 for –NH2 of starting materials and at the
same time appearance of band at 1610-1635 cm-1 which is
characteristic for -CH=N group.31 The formation of title
compounds (11-20) were confirmed by the disappearance
of the absorption maxima at 3330-3400 cm-1, which are
ascribed to the vibrations of NH group of the indole ring;
at the same time the appearance of a new maximum at
1360-1380 cm-1, which is characteristic for indolo[1,2-c]
quinazoline ring with a tertiary nitrogen atom, appears.32
The exhibited chemical shifts obtained from 1H NMR
spectra of compounds 1-20 supported the proposed
structures of the compounds.1H NMR of A showed a
singlet at d 6.4 ppm, characteristic for –NH2 group of amino
phenyl ring and other singlet at d 8.48 ppm, characteristic
for –NH group of indolyl ring.16 The condensation between
A and aldehydes (a-j) was confirmed by the disappearance
of signals at d 6.4 corresponding to NH2 protons of
compound A and appearance of signals at d 8.16-8.29 which
is due to CH=N protons. Finally, in the title compounds
disappearance of signals corresponding to –NH of indolyl
ring and CH=N protons supports the indoloquinazoline
ring structure.32
Further, 13C NMR spectra showed confirmatory signals
of the C=N carbon atoms and the aromatic carbons in
the range of 148.9-167.9 ppm and 110.7-157.9 ppm
respectively.33
The structures of all intermediates and title compounds
were further confirmed by mass spectral analysis.
ESI-MS spectra of all the compounds showed a single peak
suggesting the molecular formulae. In addition, the FAB
mass spectrum of compound (11) shows a parent peak
at m/z (M+) 294 (100%), which confirms the proposed
formula C21H14N2. The major fragments were observed
at m/z values of 217 (34.5%), 192 (65.2%), 191 (85.5%),
179 (48.2%), 77 (12.5%) and 76 (22.8%) which indicate
the fragmentation pattern of compound 11.
the inhibition zone at the end of 24 h for bacteria and
72 h for fungi. Each experiment was repeated thrice and
the average of the three independent determinations was
recorded. Screening results are summarized in Table 1.
The antimicrobial screening revealed that some of the
compounds (15-20) showed high activity against all
bacterial and fungal strains. In particular, bis-indolo[1,2-c]
quinazolines (19 and 20) showed excellent activity against
all tested strains.
Determination of minimum inhibitory concentration (MIC)
The minimum inhibitory concentration of potent
compounds (15-20) against all bacterial and fungal strains
was determined by liquid dilution method.34-36 Stock
solutions of tested compounds with 2.5, 5, 10, 15, 20, 25,
30, 35, 40, 45 and 50 µg mL-1 concentrations were prepared
with appropriate solvent. The solutions of standard drugs,
Ampicillin and Ketoconazole were prepared in the same
concentrations. Inoculums of the bacterial and fungal
culture were also prepared. To a series of tubes containing
1 mL each of quinazoline compound solution with different
concentrations and 0.2 mL of the inoculums was added.
Further 3.8 mL of the sterile water was added to each of
the test tubes. These test tubes were incubated for 24 h and
observed for the presence of turbidity. This method was
repeated by changing quinazoline compounds with standard
drugs Ampicillin and Ketoconazole for comparison. The
minimum inhibitory concentration at which no growth
was observed was taken as the MIC values (Table 2). The
comparison of the MICs (in µg mL-1) of potent compounds
and standard drugs against tested strains are presented in
Figure 1. It was found that 15-18 compounds have highest
activity against all bacterial and fungal strains with MIC
value (2.5-15 µg mL-1). Furthermore, bis-indolo[1,2-c]
quinazolines (19 and 20) exhibited potent inhibitory activity
(MIC range 2.5-5 µg mL-1) against all the bacterial and
fungal strains even than standard drugs Ampicillin and
Ketoconazole.
Biological study
Conclusions
Antimicrobial activity
All the newly synthesized quinazolines were evaluated
for their in vitro antimicrobial activity against S. aureus,
B. subtilis, S. pyogenes (Gram positive), S. typhimurium,
E. coli, K. pneumonia (Gram negative) bacterial strains
and A.niger, C. albicans, T. viridae fungal strains by cup
plate method.34-36 Ampicillin and Ketoconazole were used
as standard drugs for bacteria and fungi respectively.
Preliminary screening of quinazolines and standard drugs
were performed at fixed concentrations of 1000 µg mL-1.
Inhibition was recorded by measuring the diameter of
In this report, easy and useful method to obtain
biologically active mono and bis-6-substituted
indolo[1,2-c]quinazoline derivatives have been presented
and all the synthesized compounds were screened for
their antimicrobial activity against different bacterial and
fungal strains. From the antimicrobial data it seems that
compounds which contain two quinazoline moieties in
their structures (19 and 20) and heterocyclic moiety at C6
position (15-20) seem to be more potent even than standard
drugs ampicillin and ketoconazole.

900
Synthesis of Some New Mono, Bis-Indolo[1, 2-c]quinazolines
J. Braz. Chem. Soc.
Table 1. Zone of inhibition of newly synthesized 6-arylindolo[1,2-c]quinazolines (11-20) against different bacteria and fungi
Zone of inhibition / mm
Gram-negative bacteria
Compound
(1000 µg mL-1)
Gram-positive bacteria
Fungi
S. aureus
B. subtilis
15
S. pyogenes S. typhimurium
E. coli
20
K. pneumonia
A. niger
21
C. albicans
T. viridae
18
11
12
13
14
15
16
17
18
19
20
Std
21
18
9
18
14
21
13
48
46
50
49
51
50
35a
12
18
21
19
49
50
46
51
55
52
45a
18
9
20
19
16
21
48
50
49
50
51
52
40b
19
15
15
18
20
12
21
19
50
49
50
50
51
49
45a
18
12
12
48
51
49
50
52
55
48a
16
19
14
11
50
51
46
45
49
48
49
50
46
45
50
46
51
50
48
49
52
52
52
55
48
39a
51
40a
50
45b
51
41b
aAmpicillin; bKetoconazole.
Table 2. MIC values of potent 6-arylindolo[1,2-c]quinazolines (15-20) and standard drugs
MIC / (µg mL-1)
Compound
Gram-positive bacteria
Gram-negative bacteria
Fungi
S. aureus
B. subtilis
S. pyogenes S. typhimurium
E. coli
5
K. pneumonia
A. niger C. albicans T. viridae
15
16
17
18
19
20
Std
10
2.5
5
2.5
10
10
2.5
2.5
5
10
15
2.5
5
10
5
2.5
5
10
10
2.5
5
15
5
15
5
10
15
5
10
5
5
15
5
10
5
5
5
2.5
2.5
10a
2.5
2.5
2.5
10a
2.5
2.5
2.5
10a
2.5
5
2.5
5
25a
5
15a
5
15b
2.5
25b
5
20b
20a
aAmpicillin; bKetoconazole.
Figure 1. Comparison of MIC values (in µg mL-1) of quinazolines and standard drugs against different bacteria and fungi.
Experimental
data was obtained by using a Perkin-Elmer 2400 CHN
elemental analyzer. The IR spectra were recorded in KBr
pellets on Perkin- Elmer-283 spectrophotometer. 1H NMR
spectra were acquired at 400 MHz, and 13C NMR at 67.93
MHz on a Bruker NMR spectrometer (Bruker Bioscience,
All solvents used were of analytical grade. TLC analysis
was done using precoated silica gel plates and visualization
was done using iodine vapors. Micro analytical (C, N, H)

Vol. 21, No. 5, 2010
Rohini et al.
901
USA). FAB mass spectra were recorded on a Finnigan-
MAT 1020 instrument (Thermo Electron Corporation,
Bremen, Germany).An ion trap mass spectrometer (Agilent
Series LC/MSD Trap SL) equipped with an electrospray
ionization (ESI) source was used for MS analyses (Agilent,
PaloAlto, CA, USA). Microorganisms like Staphylococcus
aureus (ATCC 25923), Bacillus subtilis (ATCC 9372),
Streptococcus pyogenes (ATCC 19615) (Gram positive)
and Salmonella typhimurium (ATCC 14028), Escherichia
coli (ATCC 25922), Klebsiella pneumonia (ATCC 3882)
(Gram negative) bacterial strains and Aspergillus niger
(ATCC 16404), Candida albicans (ATCC 10231) and
Trichoderma viridae (IAM 5061) fungal strains were used
in the present investigation.
N-benzylidene-2-(1H-indol-2-yl)benzenamine (1)
Yield 78%; mp 196-198 C; IR (KBr) νmax/cm-1: 3400,
1650,1595,1570,1128;1HNMR(400MHz,CDCl3)dinppm
6.73 (s, 1H, Ar), 6.95-7.18 (m, 3H, Ar), 7.23-7.65 (m, 10H,
Ar), 8.10 (s, 1H, CH=N), 8.29 (s, 1H, -NH); 13C NMR (67.93
MHz, CDCl3) d 114.4, 118.6, 121.5, 123.6, 126.7, 130.2,
131.5, 132.4, 136.2, 140.1, 142.5, 143.6, 146.5, 165.3 (21C,
Ar-C); Anal. Found: C, 85.15; H, 5.51; N, 9.46%. Calc. for
C21H16N2: C, 85.11; H, 5.44; N, 9.45%. MS: [M]+ at m/z 296.
o
2-(1H-indol-2-yl)-N-(naphthalen-2-ylmethylene)
benzenamine (2)
Yield 75%; mp 222-224 oC; IR (KBr) νmax/cm-1: 3398,
1641, 1605, 1575, 1130;1H NMR (400 MHz, CDCl3) d in
ppm 6.71 (s, 1H, Ar), 6.90-7.11 (m, 2H, Ar), 7.25 -7.64
(m, 9H, Ar), 7.75 -7.94 (m, 4H, Ar), 8.16 (s, 1H, CH=N),
8.35 (s, 1H, -NH); 13C NMR (67.93 MHz, CDCl3) d 113.9,
117.9, 121.5, 123.2, 126.6, 130.2, 131.9, 132.5, 135.3,
140.8, 142,2, 145.6, 148.5, 164.9 (25C,Ar-C);Anal. Found:
C, 86.70; H, 5.22; N, 8.13%. Calc. for C25H18N2: C, 86.68;
H, 5.24; N, 8.09%. MS: [M]+ at m/z 346.
Preparation of 2-(2-aminophenyl)indzole (A)
The precursor 2-(2-aminophenyl)indole (A)
was obtained by the Fischer indole synthesis from
phenylhydrazine hydrochloride and 2-amino acetophenone
using a mixture of methane sulfonic acid and phosphorus
o
pentoxide at 85 C. All the reactions were carried out
according to the procedure described by Billimoria and
Cava.5
2-(1H-indol-2-yl)-N-((6-methoxynaphthalen-2-yl)
methylene)benzenamine (3)
Yield 79%; mp 201-203 oC; IR (KBr) νmax/cm-1: 3405,
1637, 1605, 1588, 1130, 1038, 850; 1H NMR (400 MHz,
CDCl3) d in ppm 3.90 (s, 3H, OCH3), 6.72 (s, 1H, Ar),
6.92-7.10 (m, 3H,Ar), 7.25-7.60(m, 9H,Ar), 7.73-7.82 (m,
2H, Ar), 8.15 (s, 1H, CH=N), 8.29 (s, 1H, -NH); 13C NMR
(67.93 MHz, CDCl3) d 56.2, (1C, -OCH3), 113.8, 119.5,
120.7, 123.6, 127.1, 130.2, 131.5, 132.3, 141.7, 142,2,
147.5, 151.5, 153.7, 166.9 (25C, Ar-C); Anal. Found: C,
83.01; H, 5.38; N, 7.43%. Calc. for C26H20N2O: C, 82.95;
H, 5.35; N, 7.44%. MS: [M]+ at m/z 376.
Procedure for preparation of mono-2-(2-arylideneamino
phenyl) indoles (1-10)
To a solution of precursor 2-(2-aminophenyl)indole
(A, 0.416 g, 2 mmol for 1-8 and 0.832 g, 4 mmol for
9-10) in 20-40 mL of ethanol, 2 mmol of Ar-CHO/
CHO-Ar-CHO and few drops of acetic acid was added with
vigorous stirring. The reaction mixture was then refluxed
for 3 h. After cooling, the deposited solid product was
collected by filtration and recrystalized from an ethanol/
dichloromethane-methanol mixture.
2-(1H-indol-2-yl)-N-((1-nitronaphthalen-2-yl)methylene)
benzenamine (4)
o
Procedure for preparation of 6-arylindolo[1,2-c]
quinazolines (11-20)
Yield 81%; mp 231-233 C; IR (KBr) νmax/cm-1:
3395, 1638, 1608, 1589, 1524, 1346, 1126, 850;1H NMR
(400 MHz, CDCl3) d in ppm 6.71 (s, 1H, Ar), 6.90-7.12
(m, 2H, Ar), 7.25-7.68(m, 8H, Ar), 7.93-8.02 (m, 2H, Ar),
8.16 (s, 1H, CH=N), 8.23-8.25 (m, 2H, Ar), 8.59 (s, 1H,
-NH); 13C NMR (67.93 MHz, CDCl3) d 114.2, 117.5,
119.0, 122.5, 125.2, 126.8, 132.3, 136.8, 142.1, 143.6,
147.8, 154.1, 167.2 (25C, Ar-C); Anal. Found: C, 76.80;
H, 4.56; N, 10.78%. Calc. for C25H17N3O2 : C, 76.71; H,
4.38; N, 10.74%. MS: [M]+ at m/z 391.
The final compounds mono, bis-indolo[1,2-c]
quinazolines (11-20 ) were prepared from intermediate
azomethines (1-10 ) through oxidative cyclisation method.
Powdered potassium permanganate (1.5 equiv.) was added
to a solution of the azomethyne compound (11-20) in
50-75 mL of acetone. The reaction mixture was refluxed
under heat (40-60 oC) for 30 min. It was then filtered hot,
and an equal volume of hot water added to the filtrate. The
final products, 6-substituted indolo[1,2-c]quinazolines
(11-20) rapidly separated, and was collected by filtration
and recrystalized from dimethylformamide/ethanol.
2-(1H-indol-2-yl)-N-(pyridin-2-ylmethylene)benzenamine(5)
Yield 78%; mp 185-187 oC; IR (KBr) νmax/cm-1: 3400,
1628, 1605, 1585, 1109;1H NMR (400 MHz, CDCl3) d in

902
Synthesis of Some New Mono, Bis-Indolo[1, 2-c]quinazolines
J. Braz. Chem. Soc.
ppm 6.74 (s, 1H, Ar), 6.92-7.11 (m, 3H, Ar), 7.28-7.65 (m,
8H, Ar), 8.18 (s, 1H, CH=N), 8.32 (s, 1H, -NH), 8.58 (m,
1H, Ar); 13C NMR (67.93 MHz, CDCl3) d 114.3, 118.1,
122.5, 123.6, 126.5, 130.5, 131.7, 132.9, 136.2, 141.5,
142,3, 143.4, 146.7, 148.1, 155.8, 165.9 (20C,Ar-C);Anal.
Found: C, 80.87; H, 5.09; N, 14.15%. Calc. for C20H15N3 :
C, 80.78; H, 5.08; N, 14.13%. MS: [M]+ at m/z 297.
114.2, 120.3, 123.5, 125.6, 127.1, 128.9, 130.2, 131.6,
132.8, 140.9, 142.6, 144.3, 145.7, 146.2, 146.9, 152.4
(34C, Ar-C); Anal. Found: C, 78.46; H, 4.72; N, 10.78%.
Calc. for C34H24N4S: C, 78.44; H, 4.65; N, 10.76%. MS:
[M]+ at m/z 520.
N-((6-((2-(1H-indol-2-yl)phenylimino)methyl)pyridin-2-yl)
methylene)-2-(1H-indol-2-yl)benzenamine (10)
N-((1H-pyrrol-2-yl)methylene)-2-(1H-indol-2-yl)
benzenamine(6)
Yield 78%; mp 238-240 oC; IR (KBr) νmax/cm-1: 3405,
1645, 1610, 1585, 1132; 1H NMR (400 MHz, CDCl3) d in
ppm 6.72 (s, 2H, Ar), 6.90-7.11 (m, 4H, Ar), 7.21-7.62 (m,
14H,Ar), 7.82 (m, 1H,Ar), 8.16 (s, 2H, CH=N), 8.38 (s, 2H,
-NH); 13C NMR (67.93 MHz, CDCl3) d 114.4, 114.7, 121.8,
123.2, 125.7, 127.9, 128.1,130.6, 131.3, 132.7, 141.3, 142.3,
144.8, 145.8, 146.1, 155.5, 167.9 (35 C,Ar-C)Anal. Found:
C, 81.57; H, 4.92; N, 13.63%. Calc. for C35H25N5: C, 81.53;
H, 4.89; N, 13.58%. MS: [M]+ at m/z 515.
Yield 75%; mp 205-207 oC; IR (KBr) νmax/cm-1: 3395,
3215, 1638, 1606, 1578, 1132;1H NMR (400 MHz, CDCl3)
d in ppm 6.70 (s, 1H,Ar), 6.12-7.10 (m, 5H,Ar), 7.22-7.61
(m, 6H,Ar), 8.15 (s, 1H, CH=N), 8.56 (s, 1H, -NH), 8.85 (s,
1H, pyrrolyl NH); 13C NMR (67.93 MHz, CDCl3) d 113.5,
114.2, 118.7, 120.9, 123.2, 126.6, 130.4, 131.7, 133.1,
136.7, 140.3, 141.6, 145.7, 146.2, 150.9 (19C,Ar-C);Anal.
Found: C, 80.01; H, 5.35; N, 14.82%. Calc. for C19H15N3 :
C, 79.98; H, 5.30; N, 14.73%. MS: [M]+ at m/z 285.
6-phenylindolo[1,2-c]quinazoline (11)
Yield 81%; mp 210-212 oC; IR (KBr) νmax/cm-1: 1620,
1581, 1535, 1457, 1378, 775, 741, 733; 1H NMR (400 MHz,
DMSO-d6) d in ppm 7.01-7.12 (m, 3H, Ar), 7.25-7.51 (m,
4H, Ar), 7.61-7.88 (m, 7H, Ar); 13C NMR (67.93 MHz,
DMSO-d6) d 113.2, 119.1, 120.2, 122.7, 124.4, 126.3,
127.9, 129.1, 130.5, 131.2, 132.4, 133.8, 145.4, 146.5,
152.8 (21 C, Ar-C); Anal. Found: C, 85.73; H, 4.80; N,
9.56%. Calc. for C21H14N2: C, 85.69; H, 4.79; N, 9.52%.
MS: [M]+ at m/z 294.
N-(furan-2-ylmethylene)-2-(1H-indol-2-yl)benzenamine
(7)
Yield 80%; mp 215-217 oC; IR (KBr) νmax/cm-1: 3398,
1636, 1608, 1583, 1130; 1H NMR (400MHz, CDCl3) d in
ppm 6.45 (s, 1H, Ar), 6.72 (s, 1H, Ar), 6.80-7.11 (m, 3H,
Ar), 7.29-7.61 (m, 7H, Ar), 8.14 (s, 1H, CH=N), 8.28 (s,
1H, -NH); 13C NMR (67.93 MHz, CDCl3) d 112.4, 113.9,
114.4, 120.8, 122.9, 123.4, 126.1, 130.7, 131.2, 132.5,
140.6, 142.8, 143.4, 146.2, 155.6 (19C,Ar-C);Anal. Found:
C, 79.72; H, 4.99; N, 9.86%. Calc. for C19H14N2O: C, 79.70;
H, 4.93; N, 9.78%. MS: [M]+ at m/z 286.
6-(2-naphthyl)indolo[1,2-c]quinazoline (12)
Yield 80%; mp 235-237 oC; IR (KBr) νmax/cm-1: 1625,
1585, 1530, 1459, 1385, 773, 741, 732; 1H NMR (400 MHz,
DMSO-d6) d in ppm 7.02 (m, 1H, Ar), 7.21-7.56 (m, 6H,
Ar), 7.61-7.72 (m, 3H, Ar), 7.80-8.03 (m, 5H, Ar), 8.32 (s,
1H,Ar); 13C NMR (67.93 MHz, DMSO-d6) d 112.3, 120.3,
121.4, 122.2, 123.9, 125.6, 129.1, 130.3, 132.5, 141.4,
145.5, 151.2, 156.4, 164.3 (25 C, Ar-C); Anal. Found: C,
87.20; H, 4.71; N, 8.15%. Calc. for C25H16N2: C, 87.18; H,
4.68; N, 8.13%. MS: [M]+ at m/z 344.
2-(1H-indol-2-yl)-N-(thiophen-2-ylmethylene)
benzenamine (8)
Yield 76%; mp 221-223 oC; IR (KBr) νmax/cm-1: 3395,
1638, 1610, 1586, 1132, 698; 1H NMR (400MHz,CDCl3)
d in ppm 6.73 (s, 1H,Ar), 6.92-7.14 (m, 4H,Ar), 7.28-7.62
(m, 7H, Ar), 8.16 (s, 1H, CH=N), 8.29 (s, 1H, -NH); 13C
NMR (67.93 MHz, CDCl3) d 114.5, 118.8, 120.4, 123.2,
126.8, 130.2, 131.5, 132.8, 133.3, 140.2, 143.6, 146.4,
147.8, 148.9 (19C, Ar-C); Anal. Found: C, 75.52; H, 4.69;
N, 9.28%. Calc. for C19H14N2S: C, 75.47; H, 4.67; N, 9.26%.
MS: [M]+ at m/z 302.
6-(6-methoxy-2-naphthyl)indolo[1,2-c]quinazoline (13)
Yield 78%; mp 218-220 oC; IR (KBr) νmax/cm-1: 1628,
1
1585, 1540, 1458, 1375, 1042, 775, 743, 731; H NMR
(400 MHz, DMSO-d6) d in ppm 3.90 (s, 3H, OCH3), 7.01-
7.06 (m, 2H,Ar), 7.25-7.52 (m, 5H,Ar), 7.60-8.13 (m, 7H,
Ar), 8.36 (s, 1H, Ar); 13C NMR (67.93 MHz, DMSO-d6)
d 56.4, (1C, -OCH3), 113.2, 119.8, 121.2, 122.3, 124.2,
125.8, 129.3, 130.4, 131.7, 132.6, 142.1, 145.3, 150.2,
155.9, 164.9 (25C, Ar-C); Anal. Found: C, 83.42; H, 4.89;
N, 7.50%. Calc. for C26H18N2O: C, 83.40; H, 4.85; N,
7.48%. MS: [M]+ at m/z 374.
N-((5-((2-(1H-indol-2-yl)phenylimino)methyl)thiophen-2-
yl)methylene)-2-(1H-indol-2-yl)benzenamine (9)
Yield 78%; mp 245-247 oC; IR (KBr) νmax/cm-1: 3400,
1625, 1602, 1586, 1128, 696; 1H NMR (400 MHz, CDCl3)
d in ppm 6.74 (s, 2H, Ar), 6.91-7.12 (m, 4H, Ar), 7.21 (s,
2H, Ar), 7.31-7.62 (m, 12H, Ar), 8.14 (s, 2H, CH=N), 8.32
(s, 2H, -NH); 13C NMR (67.93 MHz, CDCl3) d 113.8,

Vol. 21, No. 5, 2010
Rohini et al.
903
6-(1-nitro-2-naphthyl)indolo[1,2-c]quinazoline (14)
Yield 78%; mp 225-227 oC; IR (KBr) νmax/cm-1: 1635,
1585, 1528, 1460, 1386, 852, 775, 741, 733; H NMR
(400 MHz, DMSO-d6) d in ppm 7.04 (m, 1H,Ar), 7.28-7.42
(m, 3H, Ar), 7.58-7.73 (m, 5H, Ar), 7.85-8.12 (m, 4H, Ar),
8.28-8.40 (m, 2H, Ar); 13C NMR (67.93 MHz, DMSO-d6)
d 112.6, 119.7, 121.2, 123.5, 124.2, 125.5, 129.7, 130.3,
131.8, 141.9, 145.8, 152.4, 164.8 (25 C, Ar-C); Anal.
Found: C, 77.15; H, 3.90; N, 10.80%. Calc. for C25H15N3O2:
C, 77.11; H, 3.88; N, 10.79%. MS: [M]+ at m/z 389.
125.5, 126.4, 130.3, 131.7, 132.7, 136.9, 142.7, 145.4,
146.7, 148.2, 149.7 (19C, Ar-C); Anal. Found: C, 76.01;
H, 4.02; N, 9.35%. Calc. for C19H12N2S: C, 75.97; H, 4.03;
N, 9.33%. MS: [M]+ at m/z 300.
1
6-(5-indolo[1,2-c]quinazolin-6-yl-2-thienyl)indolo[1,2-c]
quinazoline (19)
Yield 79%; mp 250-252 oC; IR (KBr) νmax/cm-1: 1640,
1
1605, 1458, 1382, 1135, 774, 740, 732, 695; H NMR
(400 MHz, DMSO-d6) d in ppm 6.68 (s, 2H,Ar), 7.02-7.07
(m, 2H,Ar), 7.25-7.86 (m, 16H,Ar); 13C NMR (67.93 MHz,
DMSO-d6) d 110.7, 111.4, 112.6, 119.2, 120.5, 121.8,
122.8, 123.8, 126.4, 129.2, 130.6, 132.3, 133.7, 138.4,
140.7, 143.4, 145.6, 147.8, 150.2, 152.8 (34C,Ar-C);Anal.
Found: C, 79.06; H, 3.98; N, 10.85%. Calc. for C34H20N4S:
C, 79.05; H, 3.90; N, 10.84%. MS: [M]+ at m/z 516.
6-(2-pyridyl)indolo[1,2-c]quinazoline (15)
Yield 76%; mp 209-211oC; IR (KBr) νmax/cm-1: 1625,
1608, 1535, 1448, 1380, 773, 740, 733; 1H NMR (400 MHz,
DMSO-d6) d in ppm 7.02-7.05 (m, 2H, Ar), 7.21-7.72 (m,
8H,Ar), 7.82-7.86 (m, 2H,Ar), 8.69 (m, 1H,Ar); 13C NMR
(67.93 MHz, DMSO-d6) d 113.1, 120.2, 121.5, 122.9,
125.1, 126.5, 129.2, 130.6, 131.8, 133.2, 138.5, 142.3,
145.7, 146.2, 151.3, 153.5, 154.2 (20 C, Ar-C); Anal.
Found: C, 81.37; H, 4.48; N, 14.24%. Calc. for C20H13N3:
C, 81.34; H, 4.44; N, 14.23%. MS: [M]+ at m/z 295.
6-(6-indolo[1,2-c]quinazolin-6-yl-2-pyridyl)indolo[1,2-c]
quinazoline (20)
Yield 72%; mp 255-256 oC; IR (KBr) νmax/cm-1: 1628,
1606, 1586, 1385, 1128, 745, 736, 730; 1H NMR (400 MHz,
DMSO-d6) d in ppm 7.02-7.07 (m, 4H, Ar), 7.25-7.82 (m,
16H,Ar), 7.92 (t, 1H,Ar, J 7.8 Hz); 13C NMR (67.93 MHz,
DMSO-d6 ) d 112.6, 113.7, 120.8, 121.3, 122.4, 123.6,
124.6, 126.5, 128.2, 131.7, 133.4, 135.8, 139.2, 140.3,
143.9, 145.6, 148.2, 152.2, 153.7, 155.9 (35C,Ar-C);Anal.
Found: C, 82.16; H, 4.16; N, 13.72%. Calc. for C35H21N5:
C, 82.17; H, 4.14; N, 13.69%. MS: [M]+ at m/z 511.
6-(1H-2-pyrrolyl)indolo[1,2-c]quinazoline (16)
Yield 79%; mp 193-195 oC; IR (KBr) νmax/cm-1: 3215,
1
1638, 1610, 1581, 1469, 1388, 772, 743, 736; H NMR
(400 MHz, DMSO-d6) d in ppm 5.62 (m, 1H,Ar), 6.35 (m,
1H,Ar), 7.01-7.05 (m, 2H,Ar), 7.23-7.85 (m, 8H,Ar), 10.6
(s, 1H, pyrrolyl NH);; 13C NMR (67.93 MHz, DMSO-d6)
d 112.6, 113.9, 119.5, 120.7, 122.5, 124.5, 125.3, 127.1,
129.6, 130.4, 132.4, 141.7, 143.4, 145.3, 146.2, 148.3,
150.1 (19C, Ar-C); Anal. Found: C, 80.56; H, 4.68; N,
14.85%. Calc. for C19H13N3: C, 80.54; H, 4.62; N, 14.83%.
MS: [M]+ at m/z 283.
Supplementary Information
Supplementary data are available free of charge at http://
jbcs.sbq.org.br, as PDF file.
6-(2-furyl)indolo[1,2-c]quinazoline (17)
Acknowledgments
Yield 75%; mp 224-226 oC; IR (KBr) νmax/cm-1: 1640,
1608, 1579, 1470, 1388, 771, 742, 736; 1H NMR (400 MHz,
DMSO-d6) d in ppm 6.25-6.43 (m, 2H, Ar), 7.04 (m,
1H, Ar), 7.25-7.83 (m, 9H, Ar); 13C NMR (67.93 MHz,
DMSO-d6) d 112.2, 113.5, 120.8, 121.3, 122.9, 124.4,
126.5, 126.9, 130.5, 131.3, 132.5, 138.1, 142.9, 145.4,
146.5, 147.7, 149.5 (19C, Ar-C); Anal. Found: C, 80.30;
H, 4.29; N, 9.86%. Calc. for C19H12N2O: C, 80.27; H, 4.25;
N, 9.85%. MS: [M]+ at m/z 284.
The authors thank the University Grant Commission
(UGC, F.No. 34-363/2008(SR)), New Delhi, India and
National Science Council (NSC), Taiwan for financially
supporting this research.
References
1. Conchon, E.; Aboab, B.; Golsteyn, R. M.; Cruzalegui, F.;
Edmonds, T.; Leonce, S.; Pfeiffer, B.; Prudhomme, M.; Eur. J.
Med. Chem. 2006, 41, 1470.
6-(2-thienyl)indolo[1,2-c]quinazoline (18)
Yield 76%; mp 236-238 oC; IR (KBr) νmax/cm-1: 1638,
2. Via, L. D.; Gia, O.; Magno, S. M.; Settimo, A. D.; Primofiore,
G.; Settimo, F. D.; Simorini, F.; Marini, A. M.; Eur. J. Med.
Chem. 2002, 37, 475.
1
1609, 1582, 1465, 1388, 772, 743, 748, 692; H NMR
(400 MHz, DMSO-d6) d in ppm 6.45 (s, 1H,Ar), 7.01-7.05
(m, 2H,Ar), 7.28-7.85 (m, 9H,Ar); 13C NMR (67.93 MHz,
DMSO-d6) d 112.2, 119.5, 120.8, 121.5, 123.2, 124.1,
3. Lounasmaa, M.; Tolvanen, A.; Nat. Prod. Rep. 2000, 17, 175.
4. Toyota, M.; Ihara, M.; Nat. Prod. Rep. 1998, 15, 327.

904
Synthesis of Some New Mono, Bis-Indolo[1, 2-c]quinazolines
J. Braz. Chem. Soc.
5. Billimoria, A. D.; Cava, M. P.; J. Org. Chem. 1994, 59, 6777.
21. Sharma, V. M.; Prasanna, P.; Seshu, K. V. A.; Renuka, B.;
Laxman Rao, C. V.; Kumar, G.. S.; Narasimhulu, C. P.; Babu,
P. A.; Puranik, R. C.; Subramanyam, D.; Venkateswarlu, A.;
Rajagopal, S.; Kumar, K. B. S.; Rao, C. S.; Mamidi, N. V. S.
R.; Deevi, D. S.;Ajaykumar, R.; Rajagopalan, R.; Bioorg. Med.
Chem. Lett. 2002, 12, 2303.
6. Blackman, A.; Hambley, T. W.; Picker, R.; Taylor, W. C.;
Thirasana, N.; Tetrahedron Lett. 1987, 28, 5561.
7. Bhati, S. K.; Kumar, A.; Eur. J. Med. Chem. 2008, 43, 2323.
8. Sonar, V. N.; Yazadan; Khadar, S.; Sreenivasulu, N.; Indian J.
Heterocycl. Chem. 2001, 19, 299.
9. Archana, P.; Rani, K.; Bajaj, V. K.; Srivastava, R.; Chandra
Kumar, A.; Forsch, A.; Drug Res. 2003, 55, 301.
22. Hong, C.; Firestone, G. L.; Bjeldanes, L. F.; Biochem.
Pharmacol. 2002, 63, 1085.
10. Wincent, E.; Shirani, H.; Bergman, J.; Rannug, U.; Janosik, T.;
Bioorg. Med. Chem. 2009, 17, 1648.
23. Garbe, T. R.; Kobayashi, M.; Shimizu, N.; Takesue, N.; Ozawa,
M.; Yukawa, H.; J. Nat. Prod. 2000, 63, 596.
11. Sinha, D.; Tiwari, A. K.; Singh, S.; Shukl, G..; Mishra, P.;
Chandra, H.; Mishra, A. K.; Eur. J. Med. Chem. 2008, 43, 160.
12. Miert, S.V.; Hostyn, S.; Maes, B. U. M.; Cimanga, K.; Brun, R.;
Kaiser, M.; Matyus, P.; Dommisse, R.; Lemiere, G.; Vlietinck,
A.; Pieters, L.; J. Nat. Prod. 2005, 68, 674.
24. Gurkok, G.; Altanlar, N.; Suzen , S.; Chemotherapy 2009, 55,
15.
25. Rohini, R.; Shanker, K.; Reddy, P. M.; Sekhar, V. C.; Ravinder,
V.; Arch. Pharm. Chem. Life Sci. 2009, 342, 533.
26. Kiang, A. K.; Mann, F. G.; Prior, A. F.; Topham, A.; J. Chem.
Soc. 1956, 1319.
13. Bhattacharjee, A. K.; Hartell, M. G..; Nichols, D. A.; Hicks, R.
P.; Stanton, B.; van Hamont, J. E.; Milhous, W. K.; Eur. J. Med.
Chem. 2004, 39, 59.
27. Billimoria, A. D.; Cava, M. P.; Heterocycles 1996, 42, 453.
28. Frere, S.; Thiery, V.; Bailly, C.; Bessona, T.; Tetrahedron 2003,
59, 773.
14. Prudhomme, M.; Eur. J. Med. Chem. 2003, 38, 123.
15. He, L.; Chang, H.; Chou, T. C.; Savaraj, N.; Cheng, C. C.; Eur.
J. Med. Chem. 2003, 38, 101.
29. Molina, P.;Alajarin, M.;Vidal,A.; Tetrahedron 1990, 46, 1063.
30. Talbi, H.; Humbert, B.; Billaud, D.; Synth. Met. 1997, 84, 875.
31. Sahu, S. K.; Azam, M. A.; Banerjee, M.; Acharrya, S.; Behera,
C. C.; Si, S.; J. Braz. Chem. Soc. 2008, 19, 963.
32. Vostrova, L. N.; Voronina, T. A.; Karaseva, T. L.; Gernega, S.
A.; Ivanov, É. I.; Kirichenko, A. M.; Totrova, M. Yu.; Pharm.
Chem. J. 1986, 20, 404.
16. Caballero, E.; Adeva, M.; Calderon, S.; Sahagun, H.; Tome,
F.; Medarde, M.; Fernandez, J.; Lazaroc, M. L.; Ayuso, M. J.;
Bioorg. Med. Chem. 2003, 11, 3413.
17. Moreau, P.; Sancelme, M.; Bailly, C.; Leonce, S.; Pierre, A.;
Hickman, J.; Pfeiffer, B.; Prudhomme, M.; Eur. J. Med. Chem.
2001, 36, 887.
33. Jung, H. J.; Singh, N.; Jang, D. O.; Tetrahedron Lett. 2008, 49,
2960.
18. Zhu, X. Y.; Mardenborough, L. G..; Li, S.; Khan, A.; Zhang,
W.; Fan, P.; Jacob, M.; Khan, S.; Walkerb, L.; Ablordeppeya,
S. Y.; Bioorg. Med. Chem. 2007, 15, 686.
34. Reddy, P. M.; Ho, Y. P.; Shanker, K.; Rohini, R.; Ravinder, V.;
Eur. J. Med. Chem. 2009, 44, 2621.
19. Chen, Y. L.; Hung, H. M.;. Lu, C. Mi; Li, K. C.; Tzeng, C. C.;
Bioorg. Med. Chem. 2004, 12, 6539.
35. Rohini, R.; Shanker, K.; Reddy, P. M.; Ho, Y. P.; Ravinder, V.;
Eur. J. Med. Chem. 2009, 44, 3330.
20. Scovill, J.; Blank, E.; Konnick, M.; Nenortas, E.; Shapiro, T.;
Antimicrob. Agents Chemother. 2002, 46, 882.
36. Rohini, R.; Shanker, K.; Reddy, P. M.; Ravinder, V.; J. Braz.
Chem. Soc. 2010, 21, 49.
Received: May 20, 2009
Web Release Date: February 25, 2010

J. Braz. Chem. Soc., Vol. 21, No. 5, S1-S12, 2010.
Printed in Brazil - ©2010 Sociedade Brasileira de Química
0103 - 5053 $6.00+0.00
Synthesis of Some New Mono, Bis-Indolo[1, 2-c]quinazolines:
Evaluation of their Antimicrobial Studies
Rondla Rohini,a,c P. Muralidhar Reddy,a,b Kanne Shanker,a
Anren Hu*,c and Vadde Ravinder*,a
aDepartment of Chemistry, Kakatiya University, Warangal-506 009, A.P, India
bDepartment of Chemistry, National Dong Hwa University, Hualien, Taiwan
cDepartment of Laboratory Medicine and Biotechnology, Tzu Chi University, Hualien, Taiwan
Antibacterial Activity
1000 µg. The plates were allowed to stand for an hour in
order to facilitate the diffusion of the drug solution. Then
the plates were incubated at 37 oC for 24 hours. The zones
of inhibition against all the microorganisms were measured
in millimeters.
Antibacterial testing was performed by cup plate
method.Nutrient broth was prepared by dissolving peptone
(0.5%), yeast extract (0.15%), beef extract (0.15%), sodium
chloride (0.36%), and monopotassium phosphate (0.13%)
in distilled water (100 mL). The pH of the solution was
adjusted to 7.2 by adding sodium hydroxide solution (4%)
and the resulting solution was autoclaved for 20 min at
15 psi. One day prior to the experiment, the cultures against
Staphylococcus aureus, Bacillus subtilis, Streptococcus
pyogenes,Salmonella typhimurium, Escherichia coli and
Klebsiella pneumonia were inoculated in nutrient broth
(inoculation medium) and incubated overnight at 37
oC. Nutrient agar medium was prepared by dissolving
peptone (1%), yeast extract (0.6%), beef extract (0.5%),
and sodium chloride (0.5%) in distilled water. The pH of
the solution was adjusted to 7.2 by adding 4% aqueous
sodium hydroxide solution. Agar (2.4%) was then added
and the whole solution was autoclaved for 20 min at 15 psi.
Preliminary screening for ten quinazolines was performed
at fixed concentrations of 1000 µg mL-1. Inoculation
medium containing 24 h grown culture was added
aseptically to the nutrient medium and mixed thoroughly
to get the uniform distribution. This solution was poured
(25 mL in each dish) into Petri dishes and then allowed to
attain room temperature. Thereafter, six millimeter wide
bores were made on the agar using a borer. The solutions
of test samples were added into each of the bores using
a sterile tip with micropipette. Ampicillin was used as
the standard and DMSO as the solvent control. The test
samples and the standard were tested at a concentration of
Antifungal Activity
The antifungal activity of quinazoline compounds
were tested against the pathogenic fungi Aspergillus
niger, Candida albicans, Trichoderma viridae by cup-plate
method. Nutrient agar medium was prepared by the same
method as explained under evaluation of antibacterial
activity. One and half day prior to the experiment, the
fungal cultures of Aspergillus niger, Candida albicans and
Trichoderma viridae prepared in the inoculation medium
were incubated at 37 oC for 36 h. The fungal medium was
prepared by dissolving peptone (0.5%), sodium chloride
(0.36%), monopotassium phosphate (0.13%), and glucose
(2%) in distilled water (100 mL). The pH of the solution
was adjusted to 7.2 by adding sodium hydroxide solution
(4%) and the resulting solution was autoclaved for 20 min
at 15 psi. This was cooled to 45-50 oC with gentle shaking.
One and half day, grown cultures were added aseptically
to this medium and mixed thoroughly to get uniform
distribution. The solutions of the test samples and standard
were evaluated for antifungal activity by cup-plate method
at a concentration of 1000 µg. The zone of inhibition was
measured in millimeter for the particular test sample with
each organism at 48 hours interval. Ketoconazole was used
as the standard.
*e-mail: anren@mail.tcu.edu.tw; ravichemku@rediffmail.com

S2
Synthesis of Some New Mono, Bis-Indolo[1, 2-c]quinazolines
J. Braz. Chem. Soc.
Figure S1. 1H NMR spectrum of 6-phenyl indolo[1,2-c]quinazoline (11).
Figure S2. 13C NMR spectrum of 6-phenyl indolo[1,2-c]quinazoline (11).

Vol. 21, No. 5, 2010
Rohini et al.
S3
Figure S3. 1H NMR spectrum of 6-phenyl indolo[1,2-c]quinazoline (12).
Figure S4. 13C NMR spectrum of 6-phenyl indolo[1,2-c]quinazoline (12).

S4
Synthesis of Some New Mono, Bis-Indolo[1, 2-c]quinazolines
J. Braz. Chem. Soc.
Figure S5. 1H NMR spectrum of 6-phenyl indolo[1,2-c]quinazoline (13).
Figure S6. 13C NMR spectrum of 6-phenyl indolo[1,2-c]quinazoline (13).

Vol. 21, No. 5, 2010
Rohini et al.
S5
Figure S7. 1H NMR spectrum of 6-phenyl indolo[1,2-c]quinazoline (14).
Figure S8. 13C NMR spectrum of 6-phenyl indolo[1,2-c]quinazoline (14).

S6
Synthesis of Some New Mono, Bis-Indolo[1, 2-c]quinazolines
J. Braz. Chem. Soc.
Figure S9. 1H NMR spectrum of 6-phenyl indolo[1,2-c]quinazoline (15).
Figure S10. 13C NMR spectrum of 6-phenyl indolo[1,2-c]quinazoline (15).

Vol. 21, No. 5, 2010
Rohini et al.
S7
Figure S11. 1H NMR spectrum of 6-phenyl indolo[1,2-c]quinazoline (16).
Figure S12. 13C NMR spectrum of 6-phenyl indolo[1,2-c]quinazoline (16).

S8
Synthesis of Some New Mono, Bis-Indolo[1, 2-c]quinazolines
J. Braz. Chem. Soc.
Figure S13. 1H NMR spectrum of 6-phenyl indolo[1,2-c]quinazoline (17).
Figure S14. 13C NMR spectrum of 6-phenyl indolo[1,2-c]quinazoline (17).

Vol. 21, No. 5, 2010
Rohini et al.
S9
Figure S15. 1H NMR spectrum of 6-phenyl indolo[1,2-c]quinazoline (18).
Figure S16. 13C NMR spectrum of 6-phenyl indolo[1,2-c]quinazoline (18).

S10
Synthesis of Some New Mono, Bis-Indolo[1, 2-c]quinazolines
J. Braz. Chem. Soc.
Figure S17. 1H NMR spectrum of 6-phenyl indolo[1,2-c]quinazoline (19).
Figure S18. 13C NMR spectrum of 6-phenyl indolo[1,2-c]quinazoline (19).

Vol. 21, No. 5, 2010
Rohini et al.
S11
Figure S19. 1H NMR spectrum of 6-phenyl indolo[1,2-c]quinazoline (20).
Figure S20. 13C NMR spectrum of 6-phenyl indolo[1,2-c]quinazoline (20).

S12
Synthesis of Some New Mono, Bis-Indolo[1, 2-c]quinazolines
J. Braz. Chem. Soc.
Figure S21. FAB mass spectrum of 6-phenyl indolo[1,2-c]quinazoline (11).
N
N
N
m/z 217
m/z 179
N
N
m/z 77
m/z 76
m/z 294
N
NH
m/z 191
m/z 192
Scheme S1. FAB mass fragmentation pattern of 6-phenyl indolo[1,2-c]quinazoline (11).