Synthesis and antimicrobial activity of some 5-substituted-3-phenyl-N β-(substituted-2-oxo-2H-pyrano[2,3-b]quinoline-3-carbonyl) -1H-indole-2-carboxyhydrazide

Article abstract of DOI:10.1248/cpb.57.557

Ethyl 3-oxo-3-{2-[(5-substituted-3-phenyl-1H-indol-2-yl)carbonyl] hydrazinyl}propanoates 5a-b were synthesized according to the literature method. These on further reaction with substituted-2-hydroxy-3-formylquinolines 3a-e yielded 5-substituted-N_β-(2-oxo-2H-pyrano[2,3-b]quinoline-3- carbonyl)-3-phenyl-1H-indole-2-carbohydrazides 6a-j. Structures of the all the newly synthesized compounds were confirmed by spectral data. All these compounds have been screened for their antibacterial activity against Staphylococcus aureus, Escherichia coli and Bacillus subtilus, antifungal activity against Aspergillus niger and Candida albicans and antituberculosis activity against Mycobacterium tuberculosis (H37R_v).

Full text of DOI:10.1248/cpb.57.557

June 2009
Chem. Pharm. Bull. 57(6) 557—560 (2009)
557
Synthesis and Antimicrobial Activity of Some 5-Substituted-3-phenyl-Nb-
(Substituted-2-oxo-2H-pyrano[2,3-b]quinoline-3-carbonyl)-1H-indole-2-
carboxyhydrazide
Basavarajaiah SULIPHAL DEVARA MATHADA and Mruthyunjayaswamy BENNIKALLU HIRE MATHADA*
Department of Studies and Research in Chemistry, Gulbarga University; Gulbarga–585106, Karnataka, India.
Received October 8, 2008; accepted March 5, 2009; published online March 16, 2009
Ethyl 3-oxo-3-{2-[(5-substituted-3-phenyl-1H-indol-2-yl)carbonyl]hydrazinyl}propanoates 5a—b were syn-
thesized according to the literature method. These on further reaction with substituted-2-hydroxy-3-formyl-
quinolines 3a—e yielded 5-substituted-Nb-(2-oxo-2H-pyrano[2,3-b]quinoline-3-carbonyl)-3-phenyl-1H-indole-2-
carbohydrazides 6a—j. Structures of the all the newly synthesized compounds were confirmed by spectral data.
All these compounds have been screened for their antibacterial activity against Staphylococcus aureus, Es-
cherichia coli and Bacillus subtilus, antifungal activity against Aspergillus niger and Candida albicans and antitu-
berculosis activity against Mycobacterium tuberculosis (H37Rv).
Key words indole; quinoline; pyrano-quinoline-2-one; antimicrobial activity
Tuberculosis is an infection caused by Mycobacterium tu- tached to b-nitrogen of 5-substituted-3-phenyl-1H-indole-2-
berculosis, which commonly affects the respiratory tract, i.e. carbohydrazide at its 3-positon via carbonyl group (Chart 1).
lungs.1) It is termed as “a global health emergency” by World These compounds are novel and hitherto unknown.
Health Organization (WHO) in 1993 as it affects 1.7 billion
people per year that is equal to one-third of the entire world Results and Discussion
population. The first line of drugs used in the treatment of
Compounds 5a, b were prepared according to the reported
tuberculosis (TB) is a combination of isoniazid, rifamycin, method.15) These compounds 5a, b when reacted with substi-
pyrazinamide and ethambutal. The high concentration of tuted-2-hydroxy-3-formyl-quinolines 3a—e in the presence
lipids in the cell wall of M. tuberculosis has been attributed of catalytic amount of piperdine in ethanol under refluxed
to its resistant to antibiotics. Thus the increasing clinical im- conditions for 5 h afforded 5-substituted-Nb-(2-oxo-2H-
portance of tuberculosis has lent additional urgency to re- pyrano[2,3-b]quinoline-3-carbonyl)-3-phenyl-1H-indole-2-
searchers to identify new effective antimycobacterial com- carbohydrazides 6a—j in a good yield. Compound 6a in its
pounds.2)
IR spectrum showed absorption bands at 1149, 1597, 1668,
Heterocycles bearing nitrogen, sulphur and oxygen atoms 1695, 1733, 3065, 3201 and 3386 cmꢀ1 due to C–O–C,
in their structure constitute the core structure of a number of CꢁN, CꢁO/CꢁO/CꢁO and NH/NH/NH functions respec-
biologically interesting compounds. Many indole derivatives tively. Three singlets and a multiplet, observed at 9.42, 9.71,
1
reported in the literature are known to possess varied biologi- 10.20 and 7.14—7.92 d in the H-NMR spectrum of com-
cal activities viz., antimalarial activity,3) antituberculosis ac- pound 6a were due to one proton of indole NH and two pro-
tivity4) and COX-2 inhibitors.5) Quinolines derivatives have
attracted the attention of the chemists because of their pres-
ence in many natural products possessing significant biologi-
cal activities.6—10) Many indolo[2,3-c]isoquinolines reported
from our laboratory have been found to possess bactericidal
and fungicidal11—13) activities. Earlier we have reported the
synthesis of 3,5-disubstituted-Nb-(2-oxobenzopyran-3-car-
bonyl)-1H-indole-2-carbohydrazide14) by making use of ethyl
3-oxo-3-{2-[(5-substituted-3-phenyl-1H-indol-2-yl)car-
bonyl]hydrazinyl}propanoates 5a, b, which in turn were pre-
pared by the reaction of 5-substituted-3-phenyl-1H-indole-2-
carbohydrazides 4a, b and diethylmalonate. In view of these
findings and in continuation of our research work on
indoles,15—18) we hereby report the synthesis and antimicro-
bial activity of some 5-substituted-Nb-(2-oxo-2H-pyrano[2,3-
b]quinoline-3-carbonyl)-3-phenyl-1H-indole-2-carbohy-
drazides 6a—j having indole and pyranoquinoline moieties
in their structure with the hope getting compound with more
potent antimicrobial and antituberculosis activity by making
use of ethyl 3-oxo-3-{2-[(5-substituted-3-phenyl-1H-indol-
2-yl)carbonyl]hydrazinyl}propanoates 5a, b and substituted-
2-hydroxy-3-formylquinolines 3a—e as starting materials
wherein substituted-2H-pyrano[2,3-b]quinoline moiety at-
Chart 1
∗ To whom correspondence should be addressed. e-mail: bhmmswamy53@rediffmail.com
© 2009 Pharmaceutical Society of Japan

558
Vol. 57, No. 6
tons of two CONH functions and fourteen aromatic protons standard drug Gentamycin at the same concentration as that
respectively. Mass spectrum of compound 6a exhibited mo- of test drugs. Compounds 6a, 6b, 6f, 6g and 6i showed good
lecular ion peak Mꢂ· at 508, 510 (33%, 12%), which corre- activity and compounds 6c, 6d, 6e, 6h, and 6j exhibited
sponds to its molecular weight. This molecular ion due to the moderate activity when compared to that of standard drug
loss of 2H-pyrano[2,3-b]quinolin-2-one molecule gave a Nystatin at the same concentration as that of test drugs
fragment ion recorded at m/z 311, 313 (48%, 19%), which on against Aspergillus niger. Compounds 6a, 6b, 6f and 6g
simultaneous expulsion of CO and N2 molecule gave another showed good activity and compounds 6c, 6d, 6e, 6h, 6i and
fragment ion recorded at m/z 255, 257 (100%, 31%) which is 6j exhibited moderate activity when compared to that of
also a base peak. This fragment ion on simultaneous loss of standard drug Nystatin at the same concentration as that of
formyl and hydrogen radicals followed by the loss of chloride test drugs against Candida albicans. Rest of the compounds
radical gave fragment ions recorded at m/z 225, 227 (24%, showed less activity against all the microorganisms tested.
9%) and 190 (36%) respectively (Chart 2). The IR, 1H-NMR Under these conditions control N,N-dimethylformamide
and mass spectral fragmentation data of compound 6a are in (DMF) did not show any antibacterial and antifungal activity.
consistancy with its structure and prove the formation of
compound 6a from compound 5a on reaction with 2-hy- compounds 6a, 6b and 6g inhibited the growth of M. tuber-
droxy-3-formylquinoline 3a. culosis at concentration 12.5 mg/ml. Compounds 6d and 6f
Antituberculosis Activity The results showed that the
Antimicrobial Activity The results showed that the exhibited moderate activity when compared to standard drug
compounds 6a, 6b, 6f and 6g showed good activity and com- streptomycin against M. tuberculosis which showed mini-
pounds 6c, 6d, 6e and 6j exhibited moderate activity against mum inhibitory concentration at 25 mg/ml. Rest of the com-
Staphylococcus aureus when compared to that of standard pounds showed activity at higher concentration when com-
drug Gentamycin at the same concentration as that of test pared to standard drug Streptomycin against the microorgan-
drugs. Compounds 6a, 6b, 6d, 6f and 6g showed good activ- ism tested. Under these conditions standard drug strepto-
ity and compounds 6c, 6e, 6h, 6i and 6j exhibited moderate mycin was sensitive at concentration 6.25 mg/ml and control
activity when compared to that of standard drug Gentamycin DMF did not show any antituberculosis activity.
at the same concentration as that of test drugs against Es-
cherichia coli. Compounds 6a, 6b, 6f and 6g showed good Conclusion
activity and compounds 6d, 6e, 6i and 6j exhibited moderate
activity against Bacillus subtilus when compared to that of
The synthesis of the target novel compounds 5-substituted-
Chart 3
Chart 2

June 2009
559
Nb-(2-oxo-2H-pyrano[2,3-b]quinoline-3-carbonyl)-3-phenyl- 3.42; N, 10.89.
5-Chloro-Nb-(7-bromo-2-oxo-2H-pyrano[2,3-b]quinoline-3-carbonyl)-3-
phenyl-1H-indole-2-carbohydrazide (6b): Pale yellow crystals in 69% yield,
mp 185 °C: IR (KBr) cmꢀ1: 1158 (C–O–C), 1593 (CꢁN), 1663, 1701, 1731
(CꢁO/CꢁO/CꢁO), 3050, 3211, 3305 (NH/NH/NH).1H-NMR in d: 6.80—
7.84 (m, 13H, ArH), 9.58 (s, 1H, indole NH), 9.95 (s, 1H, CONH), 10.19 (s,
1H, CONH). Anal. Calcd for C28H16N4O4ClBr: C, 57.19; H, 2.72; N, 9.53;
Found: C, 56.98; H, 2.58; N, 9.34.
1H-indole-2-carbohydrazide 6a—j was achieved according
to the steps indicated in Chart 1. These reactions are simple,
easily carried under normal reaction conditions and these
systems are novel and hitherto unknown.
All the newly synthesized 5-substituted-Nb-(2-oxo-2H-
pyrano[2,3-b]quinoline-3-carbonyl)-3-phenyl-1H-indole-2-
carbohydrazide 6a—j compounds tested for their antibacter-
ial activity against S. aureus, E. coli and B. substilus and an-
tifungal activity against A. niger and A. flavous. Compounds
6a, 6b, 6f and 6g showed good activity against the above mi-
croorganisms tested when compared with those of standards
Gentamycin and Nystatin which were used at the same con-
centration (1000 mg/ml in DMF) as that of test drugs.
All the newly synthesized compounds 5-substituted-Nb-(2-
oxo-2H-pyrano[2,3-b]quinoline-3-carbonyl)-3-phenyl-1H-in-
dole-2-carbohydrazides 6a—j were tested for their antituber-
culosis activity against M. tuberculosis. Compounds 6a, 6b,
6f and 6g showed good activity compared with standard drug
streptomycin.
5-Chloro-Nb-(7-methyl-2-oxo-2H-pyrano[2,3-b]quinoline-3-carbonyl)-3-
phenyl-1H-indole-2-carbohydrazide (6c): Colourless crystals in 75% yield,
mp 145 °C: IR (KBr) cmꢀ1: 1154 (C–O–C), 1564 (CꢁN), 1667, 1689, 1713
1
(CO/CO/CO), 3060, 3195, 3281 (NH/NH/NH). H-NMR in d: 1.74 (s, 3H,
CH3), 7.12—7.80 (m, 13H, ArH), 9.48 (s, 1H, indole NH), 9.84 (s, 1H,
CONH), 10.28 (s, 1H, CONH). Anal. Calcd for C29H19N4O4Cl: C, 66.60; H,
3.64; N, 10.71; Found: C, 66.48; H, 3.52; N, 10.55.
5-Chloro-Nb-(9-methyl-2-oxo-2H-pyrano[2,3-b]quinoline-3-carbonyl)-3-
phenyl-1H-indole-2-carbohydrazide (6d): Colourless crystals in 64% yield,
mp 191 °C: IR (KBr) cmꢀ1: 1162 (C–O–C), 1579 (CꢁN), 1668, 1695, 1723
1
(CO/CO/CO), 3061, 3187, 3258 (NH/NH/NH). H-NMR in d: 1.98 (s, 3H,
CH3), 7.21—7.91 (m, 13H, ArH), 9.18 (s, 1H, indole NH), 9.70 (s, 1H,
CONH), 10.18 (s, 1H, CONH). Anal. Calcd for C29H19N4O4Cl: C, 66.60; H,
3.64; N, 10.71; Found: C, 66.41; H, 3.48; N, 10.61.
5-Chloro-Nb-(9-methoxy-2-oxo-2H-pyrano[2,3-b]quinoline-3-carbonyl)-
3-phenyl-1H-indole-2-carbohydrazide (6e): Brown crystals in 71% yield, mp
231 °C: IR (KBr) cmꢀ1: 1162 (C–O–C), 1578 (CꢁN), 1671, 1692, 1719
1
Experimental
(CO/CO/CO), 3081, 3188, 3280 (NH/NH/NH). H-NMR in d: 2.28 (s, 3H,
Melting points were determined in open capillary tubes and are uncor-
rected. IR spectra were recorded in KBr discs (nmax in cmꢀ1) on Perkin-
Elmer FT-IR (Spectrum ONE) spectrophotometer, 1H-NMR spectra on a
Bruker AMX (400 MHz) spectrophotometer using DMSO-d6 as solvent
–OCH3), 7.32—7.98 (m, 13H, ArH), 9.61 (s, 1H, indole NH), 10.0 (s, 1H,
CONH), 10.36 (s, 1H, CONH). Anal. Calcd for C29H19N4O5Cl: C, 64.62; H,
3.53; N, 10.40; Found: C, 64.40; H, 3.35; N, 10.25.
5-Methoxy-Nb-(2-oxo-2H-pyrano[2,3-b]quinoline-3-carbonyl)-3-phenyl-
using TMS as an internal standard (chemical shifts in d) and mass spectra 1H-indole-2-carbohydrazide (6f): Pale yellow crystals in 69% yield, mp
on a mass spectrophotometer JOEL sx-102 (FAB) instrument. Compounds
were checked for their purity by TLC on silica gel G plates and spots were (CO/CO/CO), 3083, 3105, 3187 (NH/NH/NH). H-NMR in d: 2.15 (s, 3H,
located by iodine vapours.
189 °C: IR (KBr) cmꢀ1: 1166 (C–O–C), 1578 (CꢁN), 1681, 1698, 1719
1
–OCH3), 7.01—7.78 (m, 14H, ArH), 9.65 (s, 1H, indole NH), 9.91 (s, 1H,
The starting materials ethyl 3-oxo-3-{2-[(5-substituted-3-phenyl-1H- CONH), 10.28 (s, 1H, CONH). FAB-MS m/z (in %): 504 (42%), 307 (21%),
indol-2-yl)carbonyl]hydrazinyl}propanoates15) 5a, b and substituted-2-hy- 251 (100%), 221(15%), 190 (41%) (Chart 3). Anal. Calcd for C29H20N4O5:
droxy-3-formylquinolines10,11) 3a—e were papered according to reported
C, 69.05; H, 3.97; N, 11.11; Found: C, 68.80; H, 3.75; N, 11.05.
methods.
5-Methoxy-Nb-(7-bromo-2-oxo-2H-pyrano[2,3-b]quinoline-3-carbonyl)-
Synthesis of Substituted-2-chloro-3-formylquinolines 2a—e Di- 3-phenyl-1H-indole-2-carbohydrazide (6g): Brown crystals in 72% yield, mp
methyl formamide (0.006 mol) was cooled to 0 °C in a flask equipped with a
drying tube and phosphorousoxychloride (0.006 mol) was added dropwise
with stirring. To this solution acetanilide (1a—e) (0.001 mol) was added in –OCH3), 6.91—7.68 (m, 13H, ArH), 9.80 (s, 1H, indole NH), 10.28 (s, 1H,
225 °C: IR (KBr) cmꢀ1: 1154 (C–O–C), 1599 (CꢁN), 1678, 1698, 1728
(CO/CO/CO), 3058, 3108, 3281 (NH/NH/NH). H-NMR in d: 2.18 (s, 3H,
1
small portions and after 5 min the reaction mixture was heated for 16 h on
CONH), 10.57 (s, 1H, CONH). Anal. Calcd for C29H19N4O5Br: C, 59.69; H,
boiling water bath. The reaction mixture was poured into ice water and 3.26; N, 9.60; Found: C, 59.48; H, 3.14; N, 9.39.
stirred for 30 min. The solid separated was filtered, dried and recrystallized
5-Methoxy-Nb-(7-methyl-2-oxo-2H-pyrano[2,3-b]quinoline-3-carbonyl)-
from ethyl acetate to get substituted-2-chloro-3-formyl quinolines 2a—e in 3-phenyl-1H-indole-2-carbohydrazide (6h): Colourless crystals in 64%
good yield.
yield, mp 251 °C: IR (KBr) cmꢀ1: 1162 (C–O–C), 1580 (CꢁN), 1661, 1680,
1723 (CO/CO/CO), 3061, 3188, 3251 (NH/NH/NH). 1H-NMR in d: 1.71 (s,
3H, CH3), 2.20 (s, 3H, –OCH3), 7.14—7.78 (m, 13H, ArH), 9.76 (s, 1H, in-
dole NH), 10.19 (s, 1H, CONH), 10.56 (s, 1H, CONH). Anal. Calcd for
Synthesis of Substituted-2-hydroxy-3-formylquinolines 3a—e
mixture of 2-chloro-3-formylquinolines 2a—e (0.001 mol) and aqueous hy-
drochloric acid 3.5 ml (4 N) was heated under reflux conditions for 1 h and
A
then allowed to cool to room temperature. The reaction mixture was poured C30H22N4O5: C, 69.50; H, 4.25; N, 10.81; Found: C, 69.36; H, 4.15; N,
on to crushed ice and the solid separated filtered, washed with water, dried 10.60.
and recrystallized from aqueous acetic acid to get substituted-2-hydroxy-3-
5-Methoxy-Nb-(9-methyl-2-oxo-2H-pyrano[2,3-b]quinoline-3-carbonyl)-
3-phenyl-1H-indole-2-carbohydrazide (6i): Colourless crystals in 71% yield,
formylquinolines 3a—e in good yield.
Synthesis of 5-Substituted-Nb-(2-oxo-2H-pyrano[2,3-b]quinoline-3- mp 165 °C: IR (KBr) cmꢀ1: 1166 (C–O–C), 1578 (CꢁN), 1668, 1685, 1719
carbonyl)-3-phenyl-1H-indole-2-carbohydrazides 6a—j A mixture of
(CO/CO/CO), 3083, 3187, 3248 (NH/NH/NH).1H-NMR in d: 1.74 (s, 3H,
compounds ethyl 3-oxo-3-{2-[(5-substituted-3-phenyl-1H-indol-2-yl)car- CH3), 2.18 (s, 3H, –OCH3), 7.10—7.79 (m, 13H, ArH), 9.36 (s, 1H, indole
bonyl]hydrazinyl}propanoates 5a, b (0.001 mol) and various substituted-2- NH), 9.78 (s, 1H, CONH), 10.08 (s, 1H, CONH). Anal. Calcd for
hydroxy-3-formylquinolines 3a—e (0.001 mol) in ethanol (10 ml) was re- C30H22N4O5: C, 69.50; H, 4.25; N, 10.81; Found: C, 69.70; H, 4.05; N,
fluxed for 5 h in the presence of catalytic amount of piperdine. Excess of 10.58.
ethanol was removed by distillation. Crystalline residue obtained was fil-
5-Methoxy-Nb-(9-methoxy-2-oxo-2H-pyrano[2,3-b]quinoline-3-car-
tered, washed with little amount of ethanol, dried and crystallized from suit- bonyl)-3-phenyl-1H-indole-2-carbohydrazide (6j): Colourless crystals in
able solvent to afford 5-substituted-Nb-(2-oxo-2H-pyrano[2,3-b]quinoline-3- 69% yield, mp 158 °C: IR (KBr) cmꢀ1: 1162 (C–O–C), 1578 (CꢁN), 1661,
carbonyl)-3-phenyl-1H-indole-2-carbohydrazides 6a—j in good yield. The
compounds 6a, 6b, 6c, 6d, 6e and 6g were recrystallized from ethanol and 2.19 (s, 3H, –OCH3), 2.41 (s, 3H, –OCH3), 7.21—7.79 (m, 13H, ArH),
the compounds 6f, 6h, 6i and 6j were recrystallized from isopropyl alcohol.
10.00 (s, 1H, indole NH), 10.25 (s, 1H, CONH), 10.58 (s, 1H, CONH).
5-Chloro-Nb-(2-oxo-2H-pyrano[2,3-b]quinoline-3-carbonyl)-3-phenyl- Anal. Calcd for C30H22N4O6: C, 67.42; H, 4.12; N, 10.49; Found: C, 67.31;
1678, 1723 (CO/CO/CO), 3057, 3186, 3281 (NH/NH/NH).1H-NMR in d:
1H-indole-2-carbohydrazide (6a): Colourless crystals in 71% yield, mp
H, 4.19; N, 10.68.
212 °C: IR (KBr) in cmꢀ1: 1149 (C–O–C), 1597 (CꢁN), 1668, 1695, 1733
Antibacterial and Antifungal Testing Method The in vitro biological
(CO/CO/CO), 3065, 3201, 3386 (NH/NH/NH). 1H-NMR in d: 7.14—7.92 screening of the compounds 6a—j was undertaken against the bacteria S.
(m, 14H, ArH), 9.42 (s, 1H, indole NH), 9.71 (s, 1H, CONH), 10.20 (s, 1H, aureus, E. coli and B. subtilus, fungi A. niger and C. albicans by cup-plate
CONH). FAB-MS m/z (in %): 508, 510 (33%, 12%), 311, 313 (48%, 19%),
255, 257 (100%, 31%), 225, 227 (24%, 9%), 190 (36%) (Chart 2). Anal.
method14—16) using nutrient agar as medium. Then holes of 6 mm diameter
were punched carefully using a sterile cork borer and these were filled with
Calcd for C28H17N4O4Cl: C, 66.08; H, 3.34; N, 11.01; Found: C, 65.91; H, test solutions (1000 mg/ml in DMF) and DMF used as control. The plates

560
Vol. 57, No. 6
Table 1. Antimicrobial Activity of Synthesized Compounds
Zone of inhibition in mma) (activity index)
Antituberculosis
activity in MIC
(mg/ml)
Compound
Antibacterial activity (1000 mg/ml)
Antifungal activity (1000 mg/ml)
S. aureus
E. coli
B. subtilus
A. niger
C. albicans
6a
6b
6c
6d
6e
6f
6g
6h
6i
21 (0.95)
18 (0.90)
15 (0.68)
14 (0.63)
15 (0.68)
19 (0.86)
18 (0.85)
12 (0.54)
14 (0.63)
16 (0.72)
22
19 (0.95)
19 (0.90)
15 (0.75)
17 (0.85)
15 (0.75)
17 (0.85)
18 (0.90)
14 (0.70)
16 (0.80)
15 (0.75)
20
19 (0.90)
20 (0.95)
13 (0.61)
15 (0.71)
14 (0.66)
17 (0.80)
17 (0.80)
12 (0.57)
15 (0.71)
15 (0.71)
21
18 (0.85)
20 (0.90)
14 (0.63)
15 (0.68)
14 (0.63)
20 (0.90)
19 (0.86)
15 (0.68)
17 (0.77)
16 (0.72)
—
19 (0.90)
20 (0.95)
15 (0.71)
14 (0.67)
15 (0.71)
18 (0.85)
18 (0.85)
16 (0.76)
15 (0.71)
14 (0.67)
—
12.5
12.5
100
25
100
25
12.5
100
50
50
—
—
6.25
—
6j
Gentamycin
Nystatin
Streptomycin
Control (DMF)
—
—
—
—
—
—
—
—
—
22
—
—
21
—
—
a) Diameter of well (bore size), 6 mm; activity indexꢁinhibition zone of the sample/inhibition zone of the standard.
were incubated at 37 °C for 24 h in case of antibacterial activity and 72 h in
case of antifungal activity. The diameter of the zone of inhibition for all the
test compounds was measured and the results were compared with the stan-
dard drug Gentamycin for antibacterial activity and Nystatin for antifungal
activity at the same concentration (1000 mg/ml in DMF) as that of test drugs
and tabulated in Table 1.
2) Sivakumar P. M., Geeeta Babu S. K., Mukesh D., Chem. Pharma.
Bull., 55, 44—49 (2007).
3) Onyeibor O., Croft S. L., Dodson H. I., Wright C. W., J. Med. Chem.,
48, 2701—2709 (2005).
4) Guuzel O., Terzioglu N., Capan G., Salman A., Arkivoc., 12, 98—110
(2006).
Antituberculosis Testing Method In vitro antituberculosis testing was
carried out against the human virulent strain M. tuberculosis (H37Rv) by the
method of disperse culture technique using Kirchner’s medium method con-
taining Tween-80 as described by reported method.19) To sterile Kichner dis-
perse medium (4.5 ml) dispersed in borosilicate test tube (150ꢃ20 mm), was
added 0.5 ml of sterile normal bovine serum, inactivated by heating at 56 °C
for 30 min.
5) Kalgutkar A. S., Crews B. C., Saleh S., Prudhommae D., Marnett L. J.,
Bioorg. Med. Chem., 13, 6810—6822 (2005).
6) Mital A., Singh Negi V., Ramachandran U., Arkivoc., 10, 220—227
(2006).
7) Rajkumar U., Pokalwar, Rajkumar V., Hangarge, Prakash, Maske V.,
Shingare M. S., Arkivoc., 11, 196—204 (2006).
8) Klingenstein R., Melnyk P., Rutger Lelived S., Ryckebusch A., Korth
C., J. Med. Chem., 49, 5300—5308 (2006).
The compounds 6a—j under test were dissolved in DMF and added in the
form of solution in such a way as to give final concentrations of 200, 100,
50, 25, 12.5, 6.25, 3.12 and 1.56 mg per ml to the inoculums consisting of
0.1 ml of standard suspension of M. tuberculosis (H37Rv) containing
9) Srivastav A., Singh R. M., Indian J. Chem., 44B, 1868—1875 (2005).
10) Srivastava A., Chandra A., Singh R. M., Indian J. Chem., 44B, 2077—
2081 (2005).
106 bacilli/ml. The tubes were incubated at 37 °C for 8 d and then examined 11) Hiremath S. P., Saundane A. R., Swamy H. K. S., Mruthunjayaswamy
for the presence or absence of the growth of the test organism. The lowest
B. H. M., Indian J. Chem., 3B, 37—42 (1993).
concentration that showed no visible growth was taken as an end point. The 12) Hiremath S. P., Saundane A. R., Mruthunjayaswamy B. H. M., Indian
minimum inhibition concentration for all the test compounds was measured
and the results were compared with the standard drug tube with strepto-
mycin and tube with DMF used as control. The minimum inhibition concen-
tration of all the newly synthesized compounds was tabulated in the Table 1.
J. Heterocyclic Chem., 30, 603—609 (1993).
13) Hiremath S. P., Saundane A. R, Mruthunjayaswamy B. H. M., J. Indian
Chem. Soc., 72, 735—741 (1992).
14) Mruthunjayaswamy B. H. M., Shanthaveerappa B. K., Indian J. Chem.,
39B, 433—438 (2000).
Acknowledgement The authors are thankful to Directors, CDRI, Luc-
know and IISc, Bangalore for spectral data. The authors are grateful to Dr.
15) Mruthunjayaswamy B. H. M., Shanthaveerappa B. K., Indian J. Hete-
rocyclic Chem., 6, 263—270 (1997).
Kishor Bhat, Professor and Head, Department of Microbiology, MMNGH 16) Mruthunjayaswamy B. H. M., Shanthaveerappa B. K., Rajshekhar G.,
Institute of Dental Sciences & Research Centre, Belgaum-590010 for carry-
ing out the antituberculosis activity testing. Authors are also thankful to
Chairman, Department of Chemistry, Gulbarga University, Gulbarga-585106
for providing laboratory facilities.
Indian J. Chem., 37B, 453—460 (1998).
17) Mruthunjayaswamy B. H. M., Shanthaveerappa B. K., Indian J. Hete-
rocyclic Chem., 8, 31—38 (1998).
18) Basavarajaiah S. M., Mruthyunjayaswamy B. H. M., Heterocyclic
Commun., 15, (2009) (in press).
References
19) Rake G, Jamvoor W. P., Mcku G. M., Amer. Rev. Tuber., 60, 121—124
(1949).
1) Thomas D., “The White Death: A History of Tuberculosis,” ISBN
0814719279 HB-ISBN 1852853328 PB, (1999).