Synthesis and antimicrobial activity of novel pyrazolo[3,4-d]pyrimidin derivatives

Article abstract of DOI:10.1016/j.ejmech.2009.12.040

Pyrazolo[3,4-d]thiazolo[3,2-a]pyrimidin-4-one derivatives have been prepared by cyclocondensation of ethyl 2-cyano-3,3-bis(methylthio)prop-2-enoate with 2-amino-4-(substitutedphenyl)thiazole to give 3-cyano-2-methylthio-4-oxo-4H-6-(substitutedphenyl)thiazolo[3,2-a]pyrimidin (2a-j) and further reacting with hydrazine hydrate to yield the target compounds (3a-j). The chemical structure of the compounds was confirmed by IR and ¹H NMR spectral data. All the compounds of the series have been screened for their antibacterial and antifungal activity studies. The result revealed that all compounds showed significant antimicrobial activity.

Full text of DOI:10.1016/j.ejmech.2009.12.040

European Journal of Medicinal Chemistry 45 (2010) 1635–1638
Contents lists available at ScienceDirect
European Journal of Medicinal Chemistry
journal homepage: http://www.elsevier.com/locate/ejmech
Short communication
Synthesis and antimicrobial activity of novel pyrazolo[3,4-d]pyrimidin derivatives
,
a
b
b
Chandrahas N. Khobragade a , Ragini G. Bodade , Shankaraiah G. Konda , Bhaskar S. Dawane ,
*
Anand V. Manwar c
a Swami Ramanand Teerth Marathawada University, School of Life Sciences, Nanded 431606, India
b Yeshwant Mahavidyalaya, Department of Chemistry, Nanded 431602, India
c Dnyanopasak College, Department of Microbiology, Parbhani 431 401, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Pyrazolo[3,4-d]thiazolo[3,2-a]pyrimidin-4-one derivatives have been prepared by cyclocondensation of
ethyl 2-cyano-3,3-bis(methylthio)prop-2-enoate with 2-amino-4-(substitutedphenyl)thiazole to give 3-
cyano-2-methylthio-4-oxo-4H-6-(substitutedphenyl)thiazolo[3,2-a]pyrimidin (2a–j) and further react-
ing with hydrazine hydrate to yield the target compounds (3a–j). The chemical structure of the
compounds was confirmed by IR and 1H NMR spectral data. All the compounds of the series have been
screened for their antibacterial and antifungal activity studies. The result revealed that all compounds
showed significant antimicrobial activity.
Received 9 January 2009
Received in revised form
5 December 2009
Accepted 18 December 2009
Available online 28 December 2009
Keywords:
Ó 2010 Elsevier Masson SAS. All rights reserved.
Pyrazolopyrimidine
Antimicrobial activity
Agar diffusion method
1. Introduction
antimicrobial screening of a novel series of pyrazolo[3,4-d]pyrim-
idine derivatives.
Emerging infectious diseases and the increasing number of
multi-drug resistant microbial pathogens still make the treatment
of infectious diseases an important and pressing global problem.
Therefore, a substantial research for the discovery and synthesis of
new classes of antimicrobial agents is needed [1,2].
2. Experimental
2.1. Materials and methods
Pyrazolopyrimidine and related heterocycles are found to
possess a wide application in the field of medicine and agriculture.
They exhibit diversified pharmacological activities like CNS
depressant [3], neuroleptic [4], tuberculostatic [5], antihyperten-
sive [6], antileishmanial [7], analgesic [8] and antimicrobial activi-
ties [9]. Some of the pyrazolopyrimidine derivatives are known to
inhibit enzymes such as xanthine oxidase [10]. The current research
is being directed towards the synthesis and improvement of bio-
logical activity of the pyrazolopyrimidine derivatives [11]. The
literature survey reveals that replacement of 1H-pyrazole of pyr-
azolo[3,4-d]pyrimidine ring system by other bioactive moieties
drastically alters its pharmacological properties [12]. Prompted by
the varied biological activities of pyrazolopyrimidine derivatives,
we envisioned our approach towards the synthesis and
All the chemicals used in the present study are of analytical
grade purchased from Himedia chemical Co. TLC was run on the
silica gel–G coated glass plates and visualized by iodine vapors. The
IR spectra were recorded on a Thermo Nicolet Nexus 670 spec-
trometer using KBr pellets. 1H NMR spectra were obtained by using
AVANCE 300 MHz spectrophotometer in DMSO-d6 using TMS as an
internal standard respectively. Melting points of synthesized
compounds were determined by a Kofler micro melting point
apparatus and were uncorrected.
2.2. Synthesis of 3-cyano-2–methylthio-4-oxo-4H–6-
(substitutedphenyl)thiazolo[3,2-a] pyrimidin (2a–j)
A reaction mixture of equimolar quantities of 2-amino-4-(sub-
stitutedphenyl)thiazolo (1 mmol) (1a–j) and ethyl 2-cyano-3,3-
bis(methylthio)prop-2-enoate (1 mmol) in 20 mL of dry DMF and 5
mL of triethylamine was refluxed for 3 h to obtain compounds 2a–j.
Progress of the reaction was monitored by TLC. The solvent was
removed in vacuo and the residue was washed with diethylether
* Corresponding author. Tel.: þ91 2462 229242.
E-mail address: cnkhobragade@rediffmail.com (C.N. Khobragade).
0223-5234/$ – see front matter Ó 2010 Elsevier Masson SAS. All rights reserved.
doi:10.1016/j.ejmech.2009.12.040

1636
C.N. Khobragade et al. / European Journal of Medicinal Chemistry 45 (2010) 1635–1638
Table 1
Spectral analysis of pyrazolo[3,4-d]thiazolo[3,2-a]pyrimidin-4-one derivatives.
Name of compound
Spectral data
3–amino-6-(4-chlorophenyl)-1H-pyrazolo[3,4-d]
thiazolo[3, 2-a]pyrimidin-4-one (3a)
Yield-65%; M.P. 204 ꢁC; IR (KBr
y
max/cmꢂ1): 3455(–NH), 3340(NH2), 3320 (–NH), 1660 (C]O), 1605
d 4.60 (bs, 2H, NH2), 7.1 (s, 1H, 5H-thiazole), 7.31–7.64(m, 4H, Ar-H), 8.6 (s,
(C]N); 1H NMR (DMSO-d6):
1H, NH).
3–amino-6-(2-hydroxyphenyl)-1H-pyrazolo[3,4-d]thiazolo
[3,2–a]pyrimidin-4-one (3b)
Yield-66%; M.P. 215 ꢁC; IR (KBr
y
max/cmꢂ1): 3460(–NH), 3330 (–NH2), 3316 (–NH), 3210(–OH), 1648
4.85 (bs, 2H, NH2), 7.08 (s, 1H, 5H-thiazole), 7.36–7.72 (m,
(C]O), 1608 (C]N); 1H NMR (DMSO-d6):
4H, Ar-H), 8.4 (s, 1H, NH), 11.56 (s,1H, OH)
Yield-64%; M.P. 220 ꢁC; IR (KBr max/cmꢂ1): 3460(–NH),3442 (–NH2), 3192 (–OH), 1649 (C]O), 1613
(C]N); 1H NMR (DMSO-d6):
4.91 (bs, 2H, NH2), 7.15 (s, 1H, 5H-thiazole), 7.31 (d, 1H, Ar-H), 7.54 (d, 1H,
Ar-H),7.82 (s, 1H, Ar-H), 8.36(s, 1H, NH), 11.46 (s, 1H, OH).
Yield-65%; M.P. 195 ꢁC; IR (KBr max/cmꢂ1): 3450(–NH), 3440(–NH2), 3327.03(–NH), 3185 (–OH), 1655
(C]O), 1608 (C]N); 1H NMR (DMSO-d6):
4.83 (bs, 2H, NH2), 7.06 (s, 1H, 5H-thiazole), 7.50 (s, 1H, Ar-
H), 7.81 (s, 1H, Ar-H), 8.51 (s, 1H, NH), 11.54 (s, 1H, OH).
d
d
3–amino-6-(5-chloro-2-hydroxyphenyl)-1H-pyrazolo[3,4-
d]thiazolo[3,2–a]pyrimidin-4-one (3c)
y
d
3–amino-6-(3-bromo-5-chloro-2-hydroxyphenyl)-1H-
pyrazolo[3,4-d]thiazolo[3,2–a]pyrimidin-4-one (3d)
y
d
3–amino-6-(4-nitrophenyl)-1H-pyrazolo[3,4-d]thiazolo
[3,2–a]pyrimidin-4-one (3e)
Yield-66%; M.P. 202 ꢁC; IR (KBr
y
max/cmꢂ1): 3442(–NH), 3398(–NH2), 2098 (N]O), 1658 (C]O), 1610
4.85 (bs, 2H, NH2), 7.12 (s, 1H, 5H-thiazole), 7.38–7.86 (m, 4H, Ar-H), 8.36
(C]N); 1H NMR (DMSO-d6):
(s, 1H, NH).
d
3–amino-6-(4-bromophenyl)-1H-pyrazolo[3,4-d]thiazolo
[3,2–a]pyrimidin-4-one (3f)
Yield-6; M.P. 202 ꢁC; IR (KBr
(C]N); 1H NMR (DMSO-d6):
(s, 1H, NH).
y
max/cmꢂ1): 3432 (NH), 3340.15 (NH2), 3210 (OH), 1660 (C]O), 1609
d
5.10 (bs, 2H, NH2), 7.16 (s, 1H, 5H-thiazole), 7.35–7.82 (m, 4H, Ar-H), 8.31
3–amino-6-(4-chloro-2-hydroxy-5-methylphenyl)-1H-
pyrazolo[3,4-d]thiazolo[3,2–a]pyrimidin-4-one (3g)
Yield-68%; M.P. 220 ꢁC; IR (KBr
(C]N); 1H NMR (DMSO-d6):
2.15 (s, 3H, CH3), 4.86 (bs, 2H, NH2), 7.05 (s, 1H, 5H-thiazole), 7.81 (s, 1H,
Ar-H), 7.42 (s, 1H, Ar-H), 8.51 (s, 1H, NH), 11.54 (s, 1H, OH).
3–amino-6-(4,5-dichloro-2-hydroxyphenyl)-1H-pyrazolo[3,4- Yield-68%; M.P. 192 ꢁC; IR (KBr max/cmꢂ1): 3410 (–NH), 3376 (–NH2), 3195 (–OH), 1655 (C]O),
1604.51 (C]N);1H NMR (DMSO-d6):
4.91 (bs, 2H, NH2), 7.16 (s, 1H, 5H-thiazole), 7.43 (s, 1H, Ar-H), 7.82
(s, 1H, Ar-H), 8.32 (s, 1H, NH), 11.82 (s, 1H, OH).
y
max/cmꢂ1): 3334(NH), 3300 (NH2), 3186 (–OH), 1665 (C]O), 1607.51
d
y
d]thiazolo[3,2-a]pyrimidin-4-one (3h)
d
3–amino-6-(4-hydroxyphenyl)-1H-pyrazolo[3,4-d]thiazolo
[3,2–a]pyrimidin-4-one (3i)
Yield-67%; M.P. 241 ꢁC; IR (KBr
y
max/cmꢂ1): 3402 (–NH), 3360 (–NH2), 3243 (OH), 1642 (C]O), 1660
d 5.05 (bs, 2H, NH2), 6.22 (s. 1H, OH), 7.05 (s, 1H, 5H-thiazole), 7.41–86 (m,
(C]N);1H NMR (DMSO-d6):
4H, Ar-H), 8.41 (s, 1H, NH).
3-amino-6-(5-chloro-2-hydroxy-3-iodophenyl)-1H-
pyrazolo[3,4-d]thiazolo[3,2–a]pyrimidin-4-one (3j)
Yield-68%; M.P. 210 ꢁC; IR (KBr
y
max/cmꢂ1): 3385(–NH), 3286 (–NH2), 3192 (–OH), 1665 (C]O),
4.87 (bs, 2H, NH2), 7.12 (s, 1H, 5H-thiazole), 7.85 (s, 1H, Ar-H),
7.51 (s, 1H, Ar-H), 8.52 (s, 1H, NH), 11.64 (s, 1H, OH).
1606.51 (C]N); 1H NMR (DMSO-d6):
d
(2 ꢀ 5 mL), recrystallized from ethanol and dried at room
dried over anhydrous sodium sulphate (Na2SO4) and the solvent
was evaporated under reduced pressure. The residue was recrys-
tallized from ethanol to afford the target compounds in 60–70%
yields. This typical experimental procedure was used to prepare the
other analogues of this series (Table 1). The spectral data confirm
the structure of the compounds.
temperature with 70–80% yield.
2.3. Synthesis of 3-amino-6-(substitutedphenyl)-1H-pyrazolo[3,4-
d]thiazolo[3,2-a]pyrimidin-4-one (3a–j)
A mixture of 3-cyano-2–methylthio-4-oxo-4H–6-(substituted-
phenyl)thiazolo[3,2-a] pyrimidine (2a–j) (1 mmol) and hydrazine
hydrate (99%) (5 mmol) in dry DMF (20 mL) was refluxed for 4 h to
obtain compounds 3a–j. The progress of the reaction was moni-
tored by TLC. After completion, the reaction mixture was extracted
with diethylether (2 ꢀ 20 mL). The combined organic layers were
2.4. Antimicrobial activity
Antimicrobial activities of synthesized compounds were tested
by agar diffusion method [13,14]. All Pathogenic strains of bacteria
and fungi were procured from Institute of Microbial Technology
Table 2
Antimicrobial activity of pyrazolo[3,4-d]thiazolo[3,2-a]pyrimidin-4-one derivatives (Zone of Inhibition in mm).
Compound
Bacteria (MIC 50
m
g/mL)
Fungi (MIC 250 mg/mL)
EC
PA
PV
SA
KN
BS
BM
SM
AN
TV
PC
AF
CA
3a
3b
3c
3d
3e
3f
3g
3h
–
–
–
11
10
14
12
12
–
–
–
–
–
–
ꢃ
ꢃ
9
–
–
–
15
–
13
9
13
–
10
–
10
–
–
–
–
–
12
14
20
–
–
–
12
–
–
–
–
–
–
21
16
18
15
16
–
–
–
17
–
15
–
12
10
16
–
–
10
9
11
16
–
–
14
–
20
20
27
26
29
27
27
22
26
21
–
26
–
23
–
13
18
12
16
21
10
17
10
–
–
–
17
–
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
25
ꢃ
32
–
12
31
16
31
18
–
25
28
32
15
32
23
29
14
–
11
11
16
10
12
18
21
–
–
–
ꢃ
ꢃ
14
ꢃ
20
–
–
ꢃ
3i
3j
30
16
25
–
11
ꢃ
–
27
–
Tetracycline
Nystatin
Control
17
–
–
18
ꢃ
17
ꢃ
14
ꢃ
–
ꢃ
–
ꢃ
ꢃ
–
ꢃ
Data represent is mean of three replicates.
EC–Escherichia coli (MTCC 1650); PV -Proteus vulgaris (MTCC 1771); PA -Pseudomonas aeruginosa (MTCC 2488);
KN–Klebsiella Pneumoniae (NCIM 2957), SA -Staphylococcus aureus (MTCC 96);
BS–Bacillus subtilis (MTCC 1789) ; SM-Serratia marcescens (MTCC 86); BM - Bacillus megaterium (MTCC 1684);
AN–Aspergillus niger (MTCC 1781); AF- Aspergillus flavus (MTCC 2501),
PC–Penicillium chrysogenum (MTCC 1996); TV - Trichoderma viridae (MTCC 167); CA - Candida albicans (MTCC 227)
Not detected -; Trace activity ꢃ.

C.N. Khobragade et al. / European Journal of Medicinal Chemistry 45 (2010) 1635–1638
1637
(IMTech) Chandigarh and National Collection of Industrial Micro-
organisms (NCIM) Pune, India. The compounds 3a–j were evalu-
ated for antimicrobial activity against some human pathogenic
bacteria viz. Bacillus megaterium (MTCC 1684), Bacillus subtilis
(MTCC 1789), Klebsiella pneumoniae (NCIM 2957), Staphylococcus
aureus (MTCC 96), Pseudomonas aeruginosa (MTCC 2488), Proteus
vulgaris (MTCC 1771), Escherichia coli (MTCC 1650) and Serratia
marcescens (MTCC 86) and fungi viz. Trichoderma viridae (MTCC
167), Penicillium chrysogenum (MTCC1996), Aspergillus flavus
(MTCC 2501), Aspergillus niger (MTCC 1781) and Candida albicans
(MTCC 227). Stock solutions of compounds were diluted in
dimethyl sulfoxide (DMSO) to give final concentrations ranging
from 50 to 1000 mg/mL. For antifungal activity, different fungal
spore suspensions in sterile distilled water were adjusted to give
a final concentration of 106 cfu/mL. An inoculum of 0.1 mL spore
suspension of each fungus was spreaded on Sabourauds Dextrose
agar plates. For antibacterial activity, Muller Hinton agar was used.
It was seeded with 0.1 mL of respective bacterial culture strains
suspension prepared in sterile saline (0.85%) of 105 cfu/mL dilution.
The wells of 6 mm diameter were filled with 0.1 mL of each
compound dilution separately for each test of fungi and bacterial
strain. The DMSO alone was used as control. The antibiotic nystatin
(30
mg/mL) and tetracycline (10 mg/mL) are used as reference
antifungal and antibacterial substance respectively for comparison.
R2
O
R1
R3
CN
EtO
N
R4
+
MeS
SMe
S
NH2
1a-j
A
R2
R1
R3
O
N
CN
N
R4
S
SMe
2a-j
B
R2
R1
R3
O
NH2
N
R4
N
S
N
N
H
3a-j
Scheme 1. General synthetic pathway followed in the preparation of compounds 3a–j. (A): DMF, TEA; (B) NH2NH2.H2O (99%), DMF. a: R1 ¼ R2 ¼ R4 ¼ H, R3 ¼ Cl, b: R1 ¼ OH, R2 ¼ R3
¼ R4 ¼ H, c: R1 ¼ OH, R2 ¼ R3 ¼ H, R4 ¼ Cl, d: R1 ¼ OH, R2 ¼ Br, R3 ¼ H, R4 ¼ Cl, e: R1 ¼ R2 ¼ R4 ¼ H, R3 ¼ NO2, f: R1 ¼ R2 ¼ R4 ¼ H, R3 ¼ Br, g: R1 ¼ OH, R2 ¼ H, R3 ¼ Cl, R4 ¼ CH3, h: R1
OH, R2 ¼ H, R3 ¼ R4 ¼ Cl, i: R1 ¼ R2 ¼ R4 ¼ H, R3 ¼ OH, j: R1 ¼ OH, R2 ¼ I, R3 ¼ H, R4 ¼ Cl.
¼

1638
C.N. Khobragade et al. / European Journal of Medicinal Chemistry 45 (2010) 1635–1638
Inoculated plates were incubated for 24 h at 37 ꢃ 0.5 ꢁC for anti-
bacterial activity and 48 h at 28 ꢃ 0.2 ꢁC for antifungal activity. The
antimicrobial activity was measured in terms of the zone of inhi-
bition in mm. Minimum inhibitory concentration (MIC) was
determined as the lowest concentration of compound which
completely inhibit the fungal and bacterial growth after incubation
time. The investigation of antimicrobial screening data revealed
that all the tested compounds showed moderate to good antimi-
crobial inhibition (Table 2).
maximum zone of inhibition (25–32 mm) than 3f and 3j.
Compound 3b was totally inactive against P. chrysogenum.
A moderate activity was given by the compounds against
remaining fungi. A. flavus and A. niger were more sensitive towards
the compounds 3a, 3c, 3f, 3g, 3h and 3i as compare to 3b, 3d, 3e.
Both of the strains were totally resistant towards the compound 3j.
C. albicans was showed good activity against the entire synthesized
compound except 3i and 3j at MIC 250
mg/mL concentration as
shown in Table 2.
In general, 100% inhibition of the fungal strains was achieved by
the compounds 3a, 3c, 3f, 3g, and 3h while remaining compounds
(3b, 3d, 3e, 3i and 3j) gives only 60–80% inhibition. The structure
activity relationship suggested that fused pyrimidines containing
imidazo and pyrazolo rings showed higher antibacterial and anti-
fungal activities than the corresponding other moieties (like tri-
azolo, halo, sulfonyl groups) [16]. Here, thiazolo moiety is
introduced along with pyrazolo rings for activity reinforcement.
Different substitutions (halo, methyl, hydroxyl, nitro) on phenyl
ring affect the antimicrobial activity of the synthesized compounds
drastically and substitution of hydroxyl groups revealed to be
crucial for antimicrobial activity. The activity is further increased
with halo substitution, particularly –Cl found to be beneficial fol-
lowed by –Br and –I. Substitutions of –NO2 and –CH3 group gives
moderate activity.
3. Results and discussion
Synthesis of a series of pyrazolo[3,4-d]thiazolo[3,2-a]pyrimidin-
4-one derivatives was carried out according to the reported
procedure [15,16]. Scheme 1 illustrates the way used for the prep-
aration of target compounds. The reaction mixture containing an
equimolar quantities of 2-amino-4-(substituted phenyl)thiazoles
1a–j and cyanoketene dithioacetal was refluxed in dry dime-
thylformamide (DMF) in presence of triethylamine (TEA) for 3 h to
yield the corresponding 3-cyano-2–methylthio-4-oxo-4H–thia-
zolo[3,2-a]pyrimidin 2a–j derivatives. The solvent was removed
from the reaction mixture and solid was treated with chloroform,
washed with water and dried over sodium sulphate. After complete
evaporation of chloroform, target compounds 3a–j were obtained
as colorless crystalline solid. All the compounds were isolated in
60–70% yield after recrystallization. The structures of the
compounds were elucidated by IR and 1H NMR spectral data. The IR
spectra of all the compounds show absorption band at 1600–1700
cmꢂ1 for C]O, 1600–1610 cmꢂ1 for C]N stretching mode. A
distinct band at 2210–2220 cmꢂ1 for C^N stretching mode in 2a–j
and between 3400 and 3500 cmꢂ1 for NH and 3300–3500 cmꢂ1 for
NH2 in 3a–j stretching mode confirms the pyrazolo ring formation.
The 1H NMR spectra of the compounds are taken in DMSO-d6
solution. NH proton of pyrazolo ring was seen at singlet in between
8.4 and 8.6 ppm and 4–5 ppm for NH2. All the compounds showed
a common OH, 5H-thiazole proton at range 11–12 and 7–8 ppm
respectively as singlet (Table 1).
4. Conclusion
In summary, the synthesized pyrazolo[3,4-d]thiazolo[3,2-
a]pyrimidin-4-one derivatives exhibit promising antimicrobial
activity. Substitution of hydroxyl and halo groups emerged as active
in both antibacterial and antifungal screening. Hence it is
concluded that there is enough scope for further study in the
developing these as good lead compounds. Moreover, this prelim-
inary study is encouraging to further explore their broad spectrum
pharmacological activities particularly enzyme inhibition.
Acknowledgement
For biological activity screening, all the test compounds were
dissolved in 1% DMSO while DMSO without test compound was
used as control, giving more or less zone of inhibition against
different microbial strains as summarized in Table 2. The results
revealed that compounds 3c and 3i displayed a good zone of
inhibition (10–31 mm) against all the selected bacterial strains
thereby exhibits interesting antibacterial activity. The remaining
compounds 3a, 3b, 3d, 3e, 3f, 3j were found to have moderate
activity, while the compounds 3g and 3h were less active. Out of
eight selected bacterial strains S. aureus and S. marcescens were
more sensitive to the compounds 3b, 3c, 3d, 3e and 3i as gives
The authors are thankful to the, Director, IICT, Hyderabad for
providing necessary instrumental facilities, Director, School of Life
Sciences, Swami Ramanand Teerth Marathawada University, Nan-
ded and Principal, Yeshwant Mahavidyalaya, Nanded for providing
the necessary facilities.
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and 3j were found to be less active while, 3g and 3h were totally
inactive to both the strains. Compounds 3a, 3c, 3d, 3e, 3f, 3g, 3h, 3i
and 3j displayed a slight activity towards the E. coli, K. pneumonia
and B. subtilis, while they were totally resistant towards 3b. B.
megaterium, P. vulgaris and P. aeruginosa were resisting to most of
the compounds at this concentration. The results were found to be
comparable with the standard tetracycline.
Further, the antifungal activity of all the synthesized compounds
was determined against pathogenic fungi viz. A. niger, A. flavus, P.
chrysogenum, T. viridae and C. albicans. Most of the compounds
were showed a significant level of antifungal activity at MIC 250 mg/
mL concentrations as compared to nystatin. Compounds 3c, 3d, 3e,
3f, 3g, 3i showed good activity against T. viridae (26–29 mm).
Similar level of activity was displayed by the compounds 3a, 3b, 3h
and 3j (20–22 mm) as compared to standard. P. chrysogenum was
affected more by the compounds 3a, 3c, 3d, 3e, 3g and 3i with
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