Synthesis, DNA binding, and antimicrobial activity of base-catalyzed 2-phenyl-3-pyrido[3,2][1,3,4]thiadiazolo [3,2]quinoline derivatives

Article abstract of DOI:10.1080/10426500802705354

A series of novel 3-{[(5-phenyl-1,3,4-thiadiazol-2-yl)imino] methyl}quinoline-2-thione (2a-c) and 2-phenyl-3-pyrido[3,2][1,3,4]thiadiazolo[3, 2]quinoline derivatives (3a-c) were prepared by a facile synthetic method using an anhydrous potassium carbonate

Full text of DOI:10.1080/10426500802705354

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Phosphorus, Sulfur, and Silicon and the
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Synthesis, DNA Binding, and
Antimicrobial Activity of Base-Catalyzed
2-Phenyl-3-pyrido[3,2][1,3,4]thiadiazolo
[3,2]quinoline Derivatives
Devappa S. Lamani a , K. R. Venugopala Reddy a , H. S. Bhojya Naik a
, Anil B. Naik b & Prakash Naik a
a Department of Studies in Industrial Chemistry , Jnana Sahyadri
Kuvempu University , Shankaraghatta, Karnataka, India
b Department of Physics , Karnataka University , Dharwad, India
Published online: 28 Dec 2009.
To cite this article: Devappa S. Lamani , K. R. Venugopala Reddy , H. S. Bhojya Naik , Anil B. Naik &
Prakash Naik (2009) Synthesis, DNA Binding, and Antimicrobial Activity of Base-Catalyzed 2-Phenyl-3-
pyrido[3,2][1,3,4]thiadiazolo [3,2]quinoline Derivatives, Phosphorus, Sulfur, and Silicon and the
Related Elements, 185:1, 1-11
To link to this article: http://dx.doi.org/10.1080/10426500802705354
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Phosphorus, Sulfur, and Silicon, 185:1–11, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802705354
SYNTHESIS, DNA BINDING, AND ANTIMICROBIAL
ACTIVITY OF BASE-CATALYZED
2-PHENYL-3-PYRIDO[3,2][1,3,4]THIADIAZOLO
[3,2]QUINOLINE DERIVATIVES
Devappa S. Lamani,1 K. R. Venugopala Reddy,1
H. S. Bhojya Naik,1 Anil B. Naik,2 and Prakash Naik1
1Department of Studies in Industrial Chemistry, Jnana Sahyadri Kuvempu
University, Shankaraghatta, Karnataka, India
2Department of Physics, Karnataka University, Dharwad, India
A series of novel 3-{[(5-phenyl-1,3,4-thiadiazol-2-yl)imino] methyl}quinoline-2-thione
(2a–c) and 2-phenyl-3-pyrido[3,2][1,3,4]thiadiazolo[3,2]quinoline derivatives (3a–c) were
prepared by a facile synthetic method using an anhydrous potassium carbonate catalyst.
The newly synthesized heterocyles were characterized by elemental analysis, FT-IR,
1H-NMR, and mass spectral data. The selected compounds were studied for interaction
with calf thymus-DNA(CT-DNA) by electronic spectra and viscosity measurements, as well
as thermal denaturation studies. Upon binding to DNA, the absorption spectrum underwent
bathochromic and hypochromic shifts. The binding constant (Kb) observed value of 8.4 ×
105 M−1 for (2a) and 8.2 × 105 M−1 for (3a) suggested that compound (2a) binds more
avidly to CT-DNA than compound (3a). The increasing viscosity of sonicated rod-like DNA
fragments and the melting temperature of DNA, in the presence of compound solutions,
support the binding mode. The synthesized derivatives have been screened for antibacterial
and antifungal activities.
Keywords Anhydrous K2CO3; anticancer agent; antimicrobial activity; DNA binding; 5-
phenyl-1,3,4-thiadiazol-2-amine; quinoline; viscosity measurements
INTRODUCTION
The pharmacological properties of quinolines and their derivatives has attracted
worldwide attention in the last few decades because of their wide occurrence in natural
products and drugs.1,2 A literature survey revealed that five- to six-membered heterocyclic
compounds containing one or two heteroatoms fused to a quinoline ring in a linear fashion
were found to possess antitumor and anticancer properties,3–5 and their cyclized prod-
ucts, e.g., triazoles,6 oxadiazoles,7 thiazolidinones,8 thiazoles,9 and thiadiazoles10 are also
associated with a broad spectrum of biological properties.
Received 16 August 2008; accepted 7 December 2008.
One of the authors (D. S. L.) thanks the Indian Institute of Science, Bangalore, and Karnataka University,
Dharwad, for providing spectral data and Kuvempu University for a awarding Research Fellowship.
Address correspondence to K. R. Venugopala Reddy, Department of Studies in Industrial Chemistry,
Jnana Sahyadri Kuvempu University, Shankaraghatta 577 451, Shimoga District, Karnataka, India. E-mail:
venurashmi30@rediffmail.com
1

2
D. S. LAMANI ET AL.
In addition, thiadiazoles in general, and 1,3,4-thiadiazoles in particular, have a
variety of applications in medicine. Heterocycles having various pharmacological and
biological activities such as antimicrobial,11–14 antitubercular,15 anti-inflammatory,16
anticonvulsant,17 antihypertensive,19 anesthetic,20 and anticancer,21 etc., have attracted
the attention of synthetic chemists. They are also well known for their applications in
agricultural and material chemistry,22 There is evidence that the anticancer activity is due
to the intercalation between the drug and the base pairs of DNA, and interference with the
normal functioning of the enzyme topoisomerase II that is involved in the breaking and
releasing of DNA strands.23 In recent years, various fused systems such as thiophene,24
furan, and pyridine analogues of ellipticine and benzothiazoloquinoline25 have been
studied for their intercalative properties. Recently, Cao and He studied DNA affinity
properties of safranine T, which features a planar phenazine ring, and they showed that
electrostatic binding plays an important role in the intercalation of safranine T.23
The recent interest in green chemistry has posed a new challenge for organic synthesis,
in that new reaction conditions need to be found that reduce the emission of volatile organic
solvents and the use of hazardous toxic chemicals. Therefore, variations have been made in
the removal of water during the cyclization. There are scattered reports of using bases such
as anhydrous AcONa, piperidene, and Et3N26,27 as desiccants for removal of water. In all
the above mentioned methods, the reaction requires prolonged heating at high temperatures
(80–90◦C) for nearly 15–18 h. In order to circumvent these difficulties, we have chosen
a radically different approach to generate new 2-phenyl-3-[1,3,4]thiadiazolo[3,2]quinoline
scaffolds by simpler methods in quantitative yields.
In continuation of our research program3,4,28,29,34 toward the synthesis of potentially
bioactive anticancer agents via a simple and practical approach, herein we report a rapid
and efficient method for the synthesis of sulfur-containing quinoline derivatives. The newly
synthesized compounds (2a) and (3a) were studied for their interactions with CT-DNA.
RESULTS AND DISCUSSION
Novel condensed heterocyclics such as 2-phenyl-3-[1,3,4]thiadiazolo[3,2]quinoline
derivatives (3a–c) can be conceivably synthesized by two pathways as shown in Scheme 1.
In the first step, various aldehydes react with 5-phenyl-1,3,4-thiadiazol-2-amine (4) using
acetic acid, which affords Schiff bases. In the second, the cyclization is achieved when the
Schiff base is refluxed with a base catalyst to yield the title compound in quantitative yield.
The desired compounds (3a–c) are obtained with high yield and short time when they have
been cyclized from compound (6) rather than from compound (5).
Our mechanistic investigations using spectral studies gave proof of cyclized and
uncyclized products. IR spectra of compounds (2a) and (3a) show the absence of an
aldehyde carbonyl stretching frequency instead it gave a band at 1657–1720 cm−1, and
sharp bands in the region of 755–760 cm−1, 1562–1567 cm−1, and 3256–3252 cm−1
1
corresponding to (C=S), ( C=N ), and ( NH ) groups, respectively.28 The H NMR
spectra (2a) show signals corresponding to (-SH- mercapto), and appeared at δ 14.05,
revealing the formation of an uncyclized product. Further, the assigned structure was
confirmed by its mass spectra with a molecular ion peak at m/z = 350 [M+]. On the other
hand the IR spectra of compound (3a) shows an absence of -OH in the region of 3462–3458
cm−1, and the reappearance of a sharp band at 1056–1054 cm−1 ( N−N ) confirmed
that cyclization had occurred. The 1H NMR spectra prompted us to confirm the subsequent

SYNTHESIS, DNA BINDING, AND ANTIMICROBIAL ACTIVITY
3
Scheme 1 Synthesis of 2-phenyl-3-[1,3,4]thiadiazolo[3,2]quinazoline derivatives.
cyclization due to the absence of aromatic OH and a halogen group present at the two
position of the quinoline nucleus.29,30 The structure assigned was confirmed by its mass
spectrum. It gave a molecular ion peak at m/z = 317 [M+H]. The spectral details of all
other compounds are given in the Experimental section.
DNA Binding Studies
The application of electronic absorption spectroscopy in CT-DNA binding studies is
a very important technique.31 The addition of increasingly higher concentrations of DNA
led to hypochromic and bathochromic (red shift) changes in its visible absorption spectra
as a result of the formation of more stable complexes (Figures 1 and 2). The interaction
of compounds (2a) and (3a) with CT-DNA resulted in a strong decrease of absorption
intensity accompanied by a shift towards higher wavelengths (∼3 and 5 nm). Around 15%
to 20%, reduction of absorption was observed at 330 nm (2a) and 300 nm for (3a) peak
maximum in the presence of an excess of calf thymus DNA. The binding of the molecules
to DNA has been well characterized by the large hypochromism. After intercalation, the
π∗ orbital of compounds could couple with π orbital of base pairs, thus decreasing the

4
D. S. LAMANI ET AL.
Figure 1 UV absorption spectra in Tris-HCl buffer upon addition of CT-DNA (2a). [DNA] = 0.5 µm, 10 µm,
drug, 20 µm; 30 µm; 40 µm; 50 µm. The arrow shows the absorbance changing upon the increase of DNA
concentration.
π∗–π transition energy and further resulting bathochromism. The change in the absorbance
values (including red shift, hypochromicity, and isosbestic point) was used to evaluate the
intrinsic binding constants (Kb). The values 8.4 × 105 M−1 for (2a) and 8.2 × 105 M−1 for
(3a) were observed. The spectral results indicate that compound (2a) binds more strongly
than (3a) (Table I).
Viscosity Measurements
To further clarify the interaction modes of (2a) and (3a) with DNA, viscosity mea-
surements were investigated. As optical phatophysical probes provide necessary but not
sufficient clues to support a binding mode, viscosity experiments are considered as one
of the least ambiguous and the most critical tests of a binding mode in solution in the
absence of crystallographic structure data. An increase in the viscosity of native DNA is
regarded as a diagnostic feature of an intercalation process.35,36 We have measured the
viscosity changes in short, rod-like DNA fragments. The relative length increase (L/L0)
of the complex formed between the compounds and DNA is shown in Figure 3. It is ev-
ident that the binding of (2a) and (3a) increased the viscosity of DNA corresponding to
an increase in the contour length of the DNA fragments. In order to elucidate the binding
mode of the present compound, the viscosity measurements were carried out on CT-DNA

SYNTHESIS, DNA BINDING, AND ANTIMICROBIAL ACTIVITY
5
Figure 2 UV absorption spectra in Tris-HCl buffer upon addition CT-DNA (3a). [DNA] = 0.5 µm, = 10µm,
drug, 20 µm; 30 µm; 40 µm; 50 µm. The arrow shows the absorbance changing upon the increase of DNA
concentration.
by varying the concentration of added compound. The effects of the compounds on the
viscosity of rod-like DNA were shown (Figure 3). The presence of the compounds had an
obvious effect on relative viscosity of CT-DNA with an increase in concentration of the
added compounds.37
Thermal Denaturation Studies
Thermal denaturation studies of CT-DNA are useful in determining the ability of
the present compounds to stabilize the double-stranded DNA. The intercalation of small
molecules into the double helix was known to increase the DNA melting temperature (Tm).
The melting temperature Tm of DNA characterizes the transition from double-stranded to
Table I Absorption spectral properties of compounds (2a) and (3a) bound to CT-DNA
Compound
λmax (nm)
Kb (M−1
)
Tm (◦C)
2a
3a
330
300
8.4 × 105
8.2 × 105
62
68

6
D. S. LAMANI ET AL.
Figure 3 Effect of increasing amount of the compounds (2a) and (3a) on the relative viscosities of CT-DNA, at
25◦C.
single-stranded nucleic acid.38,39 The DNA melting studies were carried out with CT-DNA
in the absence and presence of the compounds. The melting profiles (Tm) for CT-DNA
in the absence of the compounds had the value 60 5◦C. Under the same experimental
conditions, the presence of the compounds increased the melting temperature (Tm) about
62◦C for (2a) and 68◦C for (3a) (Figure 4). Likewise the various DNA melting experiments
strongly supported the stabilized double-stranded calf thymus DNA.34
Figure 4 Melting cures of CT-DNA in the presence and absence of (2a) and (3a).

SYNTHESIS, DNA BINDING, AND ANTIMICROBIAL ACTIVITY
7
EXPERIMENTAL
All organic solvents used for the synthesis were of analytical grade. The TLC was per-
formed on Baker-Flex silica gel 1B-F (1.55) plates using ethyl acetate and petroleum ether
(1:8). Melting points were determined on a Mel-Temp apparatus and were uncorrected. IR
1
spectra were recorded in the matrix of KBr with a Perkin-Elmer 1430 spectrometer. H
NMR spectra were recorded on a JEOL spectrometer (400 MHz), and chemical shifts (δ)
given in ppm relative to the TMS in CDCl3 solvent. Mass spectra were calculated on a
JEOL JMS-D 300 mass spectrometer operating at 70 eV. C, H, and N analyses were per-
formed at Cochin University, Sophisticated Test & Instrumentation Center, Kochi, Kerala,
India. Ammonium hexaflurophosphate (NH4PF6) was purchased from Qualigens (India).
Tris-HCl buffer (5 mM Tris-HCl, 50 mM NaCl, pH 7.2, Tris = Tris(hydroxymethyl)
amino methane) solution was prepared using deionized double distilled water. Calf thymus
DNA (CT-DNA) was purchased from Bangalore Gene, Bangalore, India. Ultraviolet-visible
absorption spectra were determined in a Perkin-Elmer model 554 UV-Vis recording spec-
trophotometer using quartz cuvettes of 10 mm path-light. 3-Formyl-2-cholroquinolines, 2-
hydroxyquinoline-3-carbaldehyde, and 3-formyl-2-mercaptoquinolines were synthesized
using reported methods.28,35
UV-Visible Absorption Studies
The concentration of CT-DNA per nucleotide [C(p)] was measured using its known
extinction coefficient at 260 nm (6600 M −1 cm−1).40 The absorbance at 260 nm (A260) and
at 280 nm (A280) for CT-DNA was measured to check purity. The ratio A260/A280 was found
to be 1.8:1.9, indicating that CT-DNA was satisfactorily free from protein. Buffer [5 mM
tris (hydroxymethyl) aminomethane, pH 7.2, 50 mM NaCl] was used for the absorption
viscosity and thermal denaturation experiments.
Absorption titration experiments were carried out by varying DNA concentration
(0–100 µM) and maintaining the compound concentration constant (30 µM). Absorption
spectra were recorded after each successive addition of DNA and equilibration (approxi-
mately 10 min). For both the compounds (2a) and (3a), observed data were then fit into
Equation (1) in order to obtain the intrinsic binding constant, Kb
[DNA]/(εa − εf ) = [DNA]/(εb − εf ) + 1/Kb (εb − εf )
(1)
where εa, ε, and εb are the apparent, free, and bound compound extinction coefficients at
330 nm (2a) and 300 nm (3a), respectively. A plot of [DNA]/(εa−εb) versus [DNA] gave
a slope of 1/(εb−εf ) and an intercept y equal to 1/Kb(εb−εf ), where Kb is the ratio of the
slope to the intercept y.41
Viscosity Measurements
Viscosity measurements were carried out using a semimicro dilution capillary vis-
cometer at room temperature. Each experiment was performed three times, and an average
flow time was calculated. Data were presented as (η/ηo) versus binding ratio, where η is
the viscosity of DNA in the presence of complex and ηo is the viscosity of DNA alone.42
Thermal Denaturation
Melting studies were carried out by monitoring the absorption of CT-DNA (50 µM)
at 260 nm at various temperatures in the presence (5–10 µM) and the absence of each

8
D. S. LAMANI ET AL.
complex. The melting temperature (Tm), at which 50% of double-stranded DNA becomes
single-stranded and the curve width (σT), in the temperature range between 10% and 90%,
absorption increases occurred and were calculated as reported.43
General Syntheses
Part A: Syntheses of 3-{[(5-phenyl-1,3,4-thiadiazol-2-yl)imino]methyl}
quinoline-2-thione (2a–c). 3-Formy-2-mercaptoquinoline (9.55 g, 0.049 mol) was re-
acted with 5-phenyl-1,3,4-thiadiazol-2-amine (8.89g 0.05mol) in 80 mL acetic acid, and was
stirred for 3–4 h at room temperature. The reaction mixture was poured onto ice-cold water.
A yellowish solid was collected by filtration and dried under vacuum and recrystallized
from ethanol. The same procedure was followed for the synthesis of reported compounds.
Yield 83%, mp 123–125◦C, IR (KBr): 3256, ( NH ), 2988, (Ar CH stretching), 1568
(C=N), 755 (C=S tautomaresed). 1H NMR (400 MHz, CDCl3) 14.05 (br.s, 1H, SH), 12.22
(br.s, 1H, NH), 10.93 (s, 1H, CH =N−), 10.23 (s, 1H, N CH-S), 7.18–8.60 (m, 10H,
Ar H). Mass spectra m/z = 350[M ], Anal. (%) for C18H14N4S2 (350), Calcd. C, 61.69;
H, 4.03; N, 15.99; S, 18.30, Found: C, 61.74; H, 4.00; N, 15.88. S,18.26.
Syntheses of 6-methyl-3-{[(5-phenyl-1,3,4-thiadiazol-2-yl)imino]methyl}
quinoline-2-thione (2b). Yellow solid with yield 77%, mp 140–142◦C, IR (KBr): 3254,
1
( NH ), 2989, (Ar CH stretching), 1566 (C=N), 756 (C=S); H NMR (400 MHz,
CDCl3) 14.06 (br, s, 1H, SH), 12.22 (br.s, 1H, NH), 10.93(s, 1H, CH =N−), 10.23
(s, 1H, N−CH−S), 2.63 (s, 3H, CH3), 7.18–8.60 (m, 9H, Ar H). Mass spectra m/z =
365[M+H], Anal. (%) for C19H16N4S2 (364.4), Calcd. C, 62.61; H, 4.42 N, 15.37; S,
17.59, Found: C, 62.74; H, 4.36; N, 15.39. S, 17.56.
Syntheses of 6-methoxy-3-{[(5-phenyl-1,3,4-thiadiazol-2-yl)imino]methyl}
quinoline-2-thione(2c). Greenish yellow solid with yield 73%, mp 155–156◦C, IR
1
(KBr): 3254, ( NH ), 2988, (Ar CH stretching), 1567 (C=N), H NMR (400 MHz,
CDCl3) 14.06 (br, s, 1H, SH), 12.22 (br.s, 1H, NH), 10.93 (s, 1H, CH =N−), 10.23 (s,
1H, N−CH−S), 2.19 (s, 3H, OCH3) 7.18–8.60 (m, 9H, Ar H). Mass spectra m/z = 380
[M+], Anal. (%) for C19H16N4OS2 (380.48), Calcd. C, 59.98; H, 4.24; N, 14.73; S, 16.85,
Found: C, 59.93; H, 4.18; N, 14.88. S, 16.91.
Part B: Syntheses of 2-phenyl-3-[1,3,4] thiadiazolo [3,2] quinoline (3a).
A 50 mL ethanolic mixture of (5) (6.15 g, 0.029 mol) was refluxed in anhydrous potas-
sium carbonate (1.25 g, 0.02 mol) for 5–7 h. The yellowish brown solid that formed was
then collected by filtration, recrystallized using ethanol, and purified by column chro-
matography using pet ether:ethyl acetate (8:3). The same procedure was followed for the
synthesis of (3b–c). Yield 73%, mp: 225–227◦C, IR (KBr): 2988, (Ar-CH stretching), 1056
1
(N−N), 1562 (C=N), H NMR (400 MHz, CDCl3) 11.05 (s, 1H, CH=N−), 10.33 (s,
1H, N−CH−S), 7.20–8.71 (m, 10H, Ar H). Mass spectra m/z = 317 [M+H], Anal. (%)
for C18H12N4S (316.3), Calcd. C, 68.33; H, 3.82; N, 17.71; S, 10.13, Found: C, 68.39; H,
3.78; N, 17.66. S, 10.16.
Syntheses of 7-Methyl-2-phenyl-3-pyrido[3,2][1,3,4]thiadiazolo[3,2]qui-
noline(3b). Brown solid with yield 68%, mp 233–235◦C, IR (KBr): 2989, (Ar CH
1
stretching),1054 (N−N), 1569 (C=N), H NMR (400 MHz, CDCl3) 11.05 (s, 1H, CH
=N−), 10.34 (s, 1H, N−CH−S), 2.68 (s, 3H, CH3) 7.20–8.70 (m, 9H, Ar H). Mass
spectra m/z = 330 [M+], Anal. (%) for C19H14N4S (330.4), Calcd. C, 69.07; H, 4.27; N,
16.96; S, 9.70, Found: C, 69.10; H, 4.31; N, 16.88. S, 9.67.

SYNTHESIS, DNA BINDING, AND ANTIMICROBIAL ACTIVITY
9
Syntheses of 7-Methoxy-2-phenyl-3-pyrido[3,2][1,3,4]thiadiazolo[3,2]
quinoline (3c). Yellowish brown solid with yield 79%, mp 240–242◦C, IR (KBr): 2989,
1
(Ar CH stretching), 1054 (N−N), 1568 (C=N), H NMR (400 MHz, CDCl3) 11.05 (s,
1H, -CH =N−), 10.34 (s, 1H, N−CH−S), 1.99 (s, 3H, OCH3) 7.18–8.70 (m, 9H, Ar H).
Mass spectra m/z = 346 [M+], Anal. (%) for C19H14N4OS (346.4), Calcd. C, 65.88; H,
4.07; N, 16.17; S, 9.26, Found: C, 65.82; H, 4.12; N, 16.22. S, 9.32.
Evaluation of Antimicrobial Activity
The in vitro antimicrobial activity was carried out against 24-h old cultures of two
bacteria and two fungi by the cup-plate method.44 Compounds were tested for their antibac-
terial activity against Pseudomonas aerugenosa and Staphylococcus aureus and antifungal
activity against Aspergillus niger and Candida albicans. Nutrient agar and potatodextrose
agars were used to culture the bacteria and fungus respectively. The compounds were tested
at a concentration of 0.005 mol/mL in DMSO solution. The solutions of Chloramphenicol
(2 mg/mL) and Flucanazole (2 mg/mL) were prepared in sterilized water and used as
standards for comparison of antibacterial and antifungal activities, respectively. The
compounds were tested at varied concentrations. The minimum inhibition concentration
was found to be 0.001 mol/mL in DMSO against all organisms. Inhibition was recorded
by measuring the diameter of the inhibition zone at the end of 24 hr fo bacteria at 28◦C and
48 h for fungus at 35◦C. Each experiment was repeated thrice, and the average of the three
independent determinations was recorded. The synthesized derivatives exhibit significant
activity, and resulting protocols are summarized in Table II. The compounds 2a, 2b, and 2c
were found to be more active against P. aerugenosa, and the compounds 2b and 2c were
found to exhibit more activity against S. aureus. The compounds 2c, 3b, and 3c against A.
niger and compounds 3b, 3c, and 2a against C. albicans exhibited significant antifungal
activity. From the results, it is evident that the uncyclized sulfur compounds (3a–c) exhibit
maximum antifungal activity compared to that of compound (2a–c), whereas cyclized
compounds (2a–c) gave more antibacterial activity than that of (3a–c).45
Chloramphenicol and fluconazole were used as standards for antibacterial and anti-
fungal activity, respectively: Control (DMSO) (−)—no activity; highly active (inhibition
zone > 12 mm); moderately active (inhibition zone 9–12 mm); slightly active (inhibition
zone 6–9 mm); inactive—inhibition zone < 6 mm.
Table II Evaluation of antimicrobial activity of 2-phenyl-3-[1,3,4]thiadiazolo[3,2] quinoline derivatives
Antibacterial activity Zone of inhibition
in mm
Antifungal activity Zone of inhibition
in mm
Compd.
P. aerugenos
S. aureus
A. niger
C. albicans
2a
2b
2c
3a
3b
3c
21
20
21
16
16
18
22
—
18
19
20
17
15
14
24
—
17
15
18
16
22
20
—
25
18
17
15
18
21
19
—
26
Chloramphenicol
Flucanazole

10
D. S. LAMANI ET AL.
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