Synthesis of some novel compounds of saccharinyl acetic acid containing nucleus and evaluation of their biological activities as antimicrobial

Article abstract of DOI:10.13005/ojc/320164

A new series of Compounds of Saccharinyl Acetic acid Containing nucleus have been prepared via an improved synthetic procedure. Where saccharinyl moiety have been introduced to 4-benzylidine-2-methyl-1,3-oxazole-5-one in position 2, compound (3) which has been reacted with nitrogen neucleophiles as hydrazine hydrate, phenyl haydrazine, aniline, p-toludine, m,p-aminobezoic acid to get compounds from (4-6). Also the reaction of compound (3) witharomatic substrate in presence of anhydrous AlCl₃ (Friedel - Crafts reaction) afforded acetamide derivative (7) via the elimination of arylidine group. Moreover saccharinyl acetic acid hydrazide (8) was refluxed in acetic anhydride to give benzisothiazole derivative (9), which reacted with carbon nuleophiles (Grignard reagent) to afford compound (10). But when compound (9) reacted with PCl₅/POCl₃ it gave compound (11) which reacted with urea and thiourea to give compound (12(a, and b)). Also the condensation of compound (9) with aromatic aldehyde gave compound (13). Structures of all synthesized compounds were elucidated from I.R., 1HNMR, mass-spectroscopy, and elemental analysis.

Full text of DOI:10.13005/ojc/320164

ISSN: 0970-020 X
CODEN: OJCHEG
2016, Vol. 32, No. (1):
Pg. 567-574
ORIENTAL JOURNAL OF CHEMISTRY
An International Open Free Access, Peer Reviewed Research Journal
www.orientjchem.org
Synthesis of Some Novel Compounds of Saccharinyl
Acetic Acid Containing Nucleus and Evaluation of
Their Biological Activities as Antimicrobial
MAgdA H. ABdELLATTIF*
Pharmaceutical Chemistry Department, Pharmacy College, Deanship of
Scientific Research, Taif University, Taif, KSA.
*Corresponding author E-mail: magdah11uk@hotmail.com
http://dx.doi.org/10.13005/ojc/320164
(Received: January 22, 2016; Accepted: March 06, 2016)
ABSTRACT
A new series of Compounds of Saccharinyl Acetic acid Containing nucleus have been
prepared via an improved synthetic procedure. Where saccharinyl moiety have been introduced to
4-benzylidine-2-methyl-1,3-oxazole-5-one in position 2 , compound (3) which has been reacted with
nitrogen neucleophiles as hydrazine hydrate , phenyl haydrazine, aniline, p-toludine, m,p-aminobezoic
acid to get compounds from (4-6). Also the reaction of compound (3) witharomatic substrate in
presence of anhydrous AlCl3 (Friedel – Crafts reaction) afforded acetamide derivative (7) via the
elimination of arylidine group. Moreover saccharinyl acetic acid hydrazide (8) was refluxed in acetic
anhydride to give benzisothiazole derivative (9), which reacted with carbon nuleophiles (Grignard
reagent) to afford compound (10).But when compound (9) reacted with PCl5/POCl3 it gave compound
(11) which reacted with urea and thiourea to give compound (12(a, and b)).Also the condensation of
compound (9) with aromatic aldehyde gave compound (13). Structures of all synthesized compounds
were elucidated from I.R., 1HNMR, mass-spectroscopy, and elemental analysis.
Key words: Saccharin, hydrazinehydrate, oxazole, imidazole, benzisothiazole.
INTROdUCTION
such as anticancer, anti tubercular, antibacterial,
and antifungal activities13-22 In view of the above
facts we report in the present work the synthesis and
antimicrobial activities of Saccharinylderivatives.
The reported pharmaceutical properties of
saccharin and its derivatives1-4 and in connection5-9
with our ongoing interest to developing new synthetic
strategies for construction of heterocyclic systems
involving saccharin due to its significant biological10-
METHOdS ANd ExpERIMENTS
12
and pharmacological activities. Also imidazole
Chemistry
derivatives are of interest to medical chemists for
many years because of their biological activities
Melting points were determined in open
capillaries using Gallen Kamp melting point

568
ABDEllATTIF, Orient. J. Chem., Vol. 32(1), 567-574 (2016)
apparatus and are uncorrected F.T.-IR spectra (KBr. that obtained was recrystallized from proper solvent
disc) were recorded on a Perkin Elmer 1720 F.T.– IR to afford (5a-d) and / or (6a-d).30
spectrometer. 1H – NMR spectra were recorded on
varin Gemini NMR spectrometer 300 MHz usingTMS (a-Saccharinyl- N- acetamido) cinnamamide
as internal standard. All reactions were monitored (5a)
by TlC using aluminum silica gel plates 60 F 245.
Yellowish (70%) ,mp 210 -212 ; IR( KBr,
Elemental analysis and antimicrobial activity were cm-1) : 1670 and 1660 (CO), 3300-3200 (NH), 1330
carried out at micro-analytical center, faculty of and 1170 (SO2) . MF C24 H19 O5 N3S’ El- MS : m/z
science, cairo university, Egypt. Elemental analysis 461 (M+) , crystallized from benzene (5b) dark brown
of all synthesized compounds is in agreement with (75%) , mp 219-221;IR( KBr cm-1).1670 (CO), 3320,
the structure elucidated.
3250 (NH) 1616 (C=N), 1320 and 1170 (SO2).
4-Benzylidene-2-Saccharinyl methyl-1,3-Oxazole-
5-one.(3)
MF C25H21O5N9S, El- MS: m/z 476 (M+1)
recrystallized from toluene.
A mixture of Saccharinyl acetic acid
chloride (10mmol) and glycine (10mmol) were
(5c) yellow (65%) ,mp 90-92 , IR(5Br, cm-
refluxed in boiling ethanol for 1hr.The spectral solid 1):1720 , ( CO) , 1680 , (CO amide), 3350-3400 (broud
was then refluxed for 4 hr. in freshly distilled acetic NH, OH) , 1310 and 1120 (SO2).MF C25H19O7N3S, EI
anhydride (30ml) and anhydrous sodium acetate in –MS: m/z 505 (M+), crystallized from benzene.
the presence of benzaldehyde.The reaction mixture
was poured onto water and solid that separated
(5d) brown ( 70%) , mp 110-112 , IR (
was re-crystallized from ethanol to give (3). Orange KBr, cm-1):1710 (CO), 1670 ( CO amide) , 3300-
0
(68%) mp 140-142 C, IR (KBr, Cm-1) : n 1700 (10 3450(broud NH, OH), 1300 and 1110 (SO2).
azlactone), 1610 (CN) , 1337 and 1120 (SO2).
EI – MS: m/z 368 [M+]. Analytical calculation for
MF C25H19O7N3S. EI – MS : m/z 505 (M+).
C18H12O5N2S; C58.7;H3.3; N7.6 found C58.65; H3.3; recrystallized from benzene.
N, 7.55.28,30
(6a) brown (75%) ,mp 180-182, IR( KBr,
5-Benzylidene–3–saccharinyl methyl-1, 2, cm-1):1660 (CO) , 1600 ( CO amidazolone) 1580
4–triazin–6–one (4a,4b)
(C=N).1330 and 1160 (SO2). MF C24 H17 O4 N3 S
A mixture of 3 ( 10mmol) and hydrazine EI- MS : m/z 443 (M+) recrystallized from toluene.
hydrate or phenyl hydrazine ( 10 mm ol) in absolute
ethanol (30 ml) was refluxed for 3hr. the solid that (6b). brown (65%) ,mp 202-204 , IR(KBr, cm-1):
obtained was recrystallized from ethanol to afford 4a: 1670 (CO), 1630 ( CO imidazole), 1580( C=N),
orange ( 75%), mp 163 -165oC ; IR (KBr, cm-1): 1700 1320 and 1170 (SO2). M.F. C25H19O4N3S. EI- MS:
(CO) , 1615 ( C=N) , 3350-3450 (br NH – NH) and m/z 457 (M+).
1337 and 1138 ( SO2) MF C18 H14 O4 N4.S EI –MS :
m/z 382 (M+). And 4b : brown ( 80%), mp 95 -97 ; IR
(6c) brown (70%), mp 150-152 , IR (KBr ,
(KBr, cm-1) : 1680 ( CO) , 1610 ( C=2), 3250 (NH), cm-1) , 1680 (coimidazolone) , 1610 (C=N), 1320 and
1330 and 1168 (SO2) MF C24H18O4N4S. EI- MS: m/z 1110 ( SO2) , 3450 (OH). MF C25 H17O6N3S EI-MS:
460 (M+)
m/z 487 (M+), recrystallized from benzene.
general procedure for the preparation of
(6d) yellowish (77%) ,mp 155-157, IR (KBr,
cinnamamide derivatives ( 5a-d) and imidazole cm-1) :1690 (Coimidazolone) , 1620 (C=N), 1280 and
one derivatives (6a-d).
A mixture of 3(10 mml ol) and aromatic
amine oraminobenzoicacid ) was reflexed for 3h. in
1120 (SO2) 3440 (OH).
M.F C25H17O6N3S. EI- MS : m/z 487 (M+)
absolute ethanol (30 ml).For compounds (5a-d) and recrystallized from toluene.
in n-nutanol (30ml) for compounds (6a-d). The solid

ABDEllATTIF, Orient. J. Chem., Vol. 32(1), 567-574 (2016)
569
general procedure for the preparation of
imidazolone derivatives(6a-d)From(saccharinyl-
N- acetamido ) cinnamide derivatives( 5a-d) by
cyclization .
The excess solvent was evaporated then
the separated compound was recrystallized from
benzene to give (7) : buff (60%) , mp 115-117 , IR
(KBr, cm-1), 1700 (CO ketone), 1680 (CO imide) ,
3340 (NH), 1330 and 1140 (SO2) MF C17H14O5N2S.
EI-MS: m/z 358 (M+)
A solution of compounds 5a-d (10 m mole)
in acetic anhydride (15ml) was boiled under reflux
for 2h. The resulting solution was poured onto
crushed ice , and the product that separated out was
filtered off, washed with solution of sodium hydrogen
carbonate followed by water and then dried. The
products were recrystallized from a proper solvent.
6- Oxo -1, 2 ,4 – triazino (4,3-b) (1,2)
benzoisothiazole(9)
A mixture of compound 8 ( 10 m mole) in
redistilled acetic anhydride 20ml was refluxed for 1h.
the reaction mixture was cooled and poured onto ice
– cold water.The solid product separated was filtered
and recrystallized from ethanol to afford compound
(9), yellowish brown (65%) , mp 145-147, IR (KBr,
cm-1) : 1710 (CO) , 3432 (OH) , 3100 (NH) 1634
(C=N) 1363 and 1133 (SO2) , HNMR (DMSo-d6) S:
2.5 (s, 2H, cH2), 4.4 (s,1H, NH) , 5.7 (s. 1H, OH of
lactam- lactim dynamic equilibrium) and 7.8-8.1 (m,
4H , ArH), MF C9H7N3O3S, EI-ms, m/z 251 (M+).
Saccharinyl (N’- benzoyl methyl) acetamide(7)
A solution of oxazolonederivative 3 (10 m
mole) in dry benzene was treated with anhydrous
Alll3(30m mole) with continuously stirring on water
bath for 3h.
The reaction mixture was decomposed with
ice- cold hydrochloric acid. Then the ethereal layer
was separated and dried over anhydrous Na2SO4.
Table 1: Antimicrobial activity (in vitro) of some synthesized
compounds
Compd no.
Zone of inhibition mm/ mg of sample
Escherickca Staphylococcus
Candida
albicans
Aspergillus
flavus
coli
aureus
3
4a
4b
5a
5b
5g
5d
6c
7
9
10a
11
0
0
18
0
0
0
12
16
15
0
19
0
0
0
12
0
0
0
14
12
10
0
0
0
17
15
15
15
16
16
0
15
15
10
10
15
0
15
0
18
0
0
0
0
0
0
0
0
0
0
12b
0
0
13a
Tetracycline
Amphotericin
18
30
0
0
28
0
0
0
16
0
0
20

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ABDEllATTIF, Orient. J. Chem., Vol. 32(1), 567-574 (2016)
general procedure for the preparation of 6 - 6- chloro -1,2,4- triazino – (4,3-b) (1,2)
alkyl–6-hydroxyl– 1,2,4- triazino (4,3-b) (1,2) benzisolhiazole(11)
benzisothiazole (10a-c).
A mixture of compound 3(10m mole) ,
To Mg metal (10m mole) in dry ether (40ml) phosphorous oxychloride ( 20m mole) and PCl5
an alkyl halide namely, ethyl iodide , methyl iodide or (1qm) was refluxed on a steam bath for 3h.
benzyl chloride (30m mole) in dry ether (20ml) was
added dropwisely.The reaction mixture was refluxed
Then poured slowly into ice – cold water.
and compound a (10m mole) in dry ether (40ml) The solid that separated was washed several times
added portion wise within 1h.
with water, dried and recrystallized from benzene
to give compound (11); brown (70%) ,mp 105-107.
The reaction mixture was further refluxed for IR(KBr, cm-1), g1630 (C=N), 1330 and 1120 (SO2)
3h, left over night and then decomposed with dil cold and no absorption for gCO and gNH.
HCl. The ethereal layer was / washed with NaHCO3
solution then water and dried over analydrous Na2
MF C9H6N3O2S C1. EI – MS’ : m/z 255 (M+)
SO4 and evaporated to give compound 10a-c which and 257 (M++2).
was recrystallized form benzene (10a) : ball yellow
(6690) , mp (195-197, IR( KB6, cm-1)) 3420 -3390 Formation of compounds ( 12 a and b)
(OH and NH) , 1610 ( C=N) , 1310 and 1130 (SO2)
, MF C10H11N3O3S, EI –MS: m/z 3(M+).
A mixture of compound 11 ( 10m mole) was
refluxed with urea and / or thio- urea ( 10 m mole )
in ( 40ml) sodium ethoxide for 3h, then cooled and
(10b) : yellowish (70%) , mp 172-174 ; IR ( KBr, poured into water.The solid that separated was dried
cm-1)
and recrystallized from benzene – ethanol (1 :1) to
: 3410 – 3380 ( OH and NH), 1600 (C=N), give 12a and for 12b.
1310 and 1110 (SO2) , ‘HNMR(DMSO-d6) S: 1.7
(t,3H,CH3) , 2.5 (q,2H,CH2) , 4(S,IH,OH), 4.5 (S,2H,
Compound (12a) : yellow (72%) , mp 72
CH2, N-CH4) , 7.8 (m, 4H , A,H) , 9.1 (S, 1H, NH). -74 . IR (KBr, cm-1) 3350 -3320 (NH), 1610 (C=N) ,
MFC11H13N3O3S. EI – HS: m/z 267 (M+).
1310 and 1120 (SO2). MF C10H9N5O3S2 EI- MS: m/2
279 (M+ ).
(10c) yellow (60%) ,mp 205-207 , IR (KBr,
cm-1) 3400-3370 (OH, and NH) , 1630 (C=N) 1320 Compound (12b) : yellowish (65%) , mp 235- 237.
and 1120 (SO2) . MF (C16H13N3O3S).
EI – MS : m/z 329 (M+)
IR ( KBr, cm-1) 3370 -3330 (NH), 1630 (C=N), 1240
(C=S) 1310 and 1120 (SO2). ‘HNMR(DMSO-d6):
O
O
O
O
R
Ac2O/Na acetate
O
3
N
OH
OH
CH2
N
Cl + H2NCH2COOH
C
S
N
ben
zal
deh
yde
1
C
ph-HC
R
3
NH
R- C
O
O
2
O
HO
R =
N
CH2
S
O2
Scheme 1:

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ABDEllATTIF, Orient. J. Chem., Vol. 32(1), 567-574 (2016)
Acetic anhydride – acetic acid (1: 1) was refluxed for
4.2 (S2H, CH2, N-CH2) , 5.9 (2S, 2H, NH2)
.3h.after concentrated, the solid that separated was
cooled and recrystallized from benzene – ethanol
(1: 1) to give (13a –c) .
7.5 (m, 4H , ArH), 8.2 (S, IH, NH). MF C10H9N5O2
S2. EI – MS : m/z 295(M+).
6- OxO -5- arylidene – 1,2,4-triazino – (4,3-b) (1,2)-
benzisothiazole (13a-c).
A mixture of compound 9 (10m mole)
and aromatic aldehyde (10m mole) namely
Benz aldehyde , p- chloro- Benz aldehyde and
anisaldehyde in (40 ml).
Compound 13a yellow (75%) ,mp 105-107.
IR (KBr, cm-1) 3400 -3360 (br. NH, OH),
1720 (CO), 1560 , 1480 (C=N, C=C), 1350 and 1150
(SO2). MF C16H11N3O3S. EI –MS : m/z 325 (M+).
CHph
O
O
CHph
NH2NHAr
Ethanol
NH
N
O
3
N
NAr
R
4
R
A
A
r
r
1
1
N
N
H
2
H
2
/
/
E
n
-
t
O
b
u
t
H
a
C
n
o
l
6
H
5
/
A
l
C
l
3
h
p
H
C
O
O
ph - CH = C - C - NHAr1
N
NAr1
Ac2O
NHCOR
5
R
6
O
Ar
R
Scheme 2
O
7
Ar = H
Ar = C6H5
R=
Ar1 =
a: CH3
b: C6H5
a : C6H5
b: C6H4CH3(p)
c:C6H5CH2 c: C6H4COOH(m)
d: C6H4COOH(p)
Scheme 2 :

ABDEllATTIF, Orient. J. Chem., Vol. 32(1), 567-574 (2016)
572
Compound 13b: yellow (75%) ,mp 200
-202. IR (KBr, cm-1) 3420-3380(br. OH and NH),
1700 (CO), 1580, 1460 ( C=N, C=C) , 1330 and
1120 (SO2), MF C16H10N3O3SC1. EI- MS: m/x 359
(M+) AND 361 (2).
theInstitute of fermentation of Osaka (IFO) namely;
theGram-positive bacteria (Staphylococcus aureus
IFO3060 and Bacillus subtilis IFO 3007), the
Gramnegativebacteria (Escherichia coli IFO 3301
andProteus vulgaris IFO 3851.
Compound 13c : ball yellow (65%) , mp
188-190. IR (KBR, cm-1) 3450- 3400 (br: OH and
NH), 1720 (CO) , 1610, 1450 (C=N, C=C), 1300 and
1110 (SO2). MF C17H10N3O4S. EI- MS: m/z 355(M+).
The primary screening was carried out
using the agar disc-diffusion method using Müller-
Hinton agar medium.24-28
RESULTS ANd dISCUSSION
Antimicrobial
The newly synthesized compounds
(3,4a-b, 5a-b, 5d, 5g, 6c, 7, 9, 10a, 11, 12b, and
13a) were tested for their in vitro growth inhibitory
activity against a panel of standard strains of
Chemistry
In the present investigation, saccharinyl
acetic acid chloride reacted with glycine to give
N- carboxymethylsaccharinylacetamide(2), which
9
NHNH2
O
CO
Ac2O
1 + NH2NH2
N
CH2
S
O2
SO2
N
8
N
HN
RMgX
O
9
P
C
SO2
l
5
/
N
P
N
O
C
l
3
HN
R
OH
10
SO2
O
N
N
NH2CHNH2
N
SO2
N
N
11
Cl
HN
NCNH2
12
R=
X=
a: O
b: S
X
a: CH3
b: C6H5
c:C6H5CH2
ArCHO
9
SO2
Ar =
a: C6H5
b: C6H4Cl
c: C6H4OCH3(p)
N
N
13
HN
CHAr
O
Scheme 3
Scheme 3 :

ABDEllATTIF, Orient. J. Chem., Vol. 32(1), 567-574 (2016)
573
reacted with benzaldehyde in the presence of
acetic anhydride and sodium acetate to give 4-
benzylidene-2-saccharinyl-methyl-1,3-oxzazole-
5-one (3). Treatment of (3) with hydrazine and/
or phenylhydrazine in refluxing ethanol afforded
5-benzylidene-3-sacchrinyl-methyl-1, 2, 4 triazine-6-
one (4a) and/or 5-benzylidene-3-sacchrinyl-methyl-
2-N-phenyl-1, 2, 4- triazine-6-one (4b).Furthermore
when compound(3) reacted with aromatic amines
(aniline, p-toludine) and aminobenzoic acids (m,
and p-aminobezoic acid) in refluxing ethanol it
gave cinnamimide derivatives (5 a-d). But when the
same reaction was carried out in n-butanol it gave
imidazolone derivatives (6a-d) which were also
obtained by refluxing compounds (5a-d) in acetic
anhydride. Moreover compound (3) undergoes acid
catalyses ring opening reaction with dry benzene
in presence of anhydrous AlCl3 (Fridel – Crafts
reaction) to give saccharinyl – (N-benzoyl-methyl)
acetamide (7), wherethe reaction product obtained
via elimination of arylidene group23, 24 On the other
to react with ethyl magnesium iodide, methyl
magnesium chloride then refluxed in dry benzene,
it afforded 6-alkyl-6-hydroxy-1,2,4-triazino-[4,3-b]
[1,2]benzisothiazole (10).Treatment of compound(9)
with mixture of POCl3/PCl5 afforded 6-Chloro-
1,2,4-triazino[4,3-b][1,2]benzisothiazole (11) which
reacted with urea and/or thiourea to give compound
(12 a and b) respectively.
Also when compound (9) was allowed
to condense with aromatic aldehyde namely
bezaldehyde, anisaldehyde, and p-chlorobezaldehde
in the presence of pyridine in a mixture of acetic
anhydride and acetic acid (1:1) it afforded 5-arylidene-
6-oxo-1,2,4-triazino-[4,3-b] benzisothiazole
(13a-c).
Antimicrobial Activity
The antimicrobial activity (in vitro) of some
synthesized compounds was determined against
some bacteria and fungi using tetracycline and
amphotericin B as standard antimicrobial agents by
using the agar diffusion method28, 29.
9
hand, when saccharinyl acetic acid hydrazide (8)
was refluxed in acetic anhydride it cyclized to 6-oxo-
1,2,4-triazino-4,3-b1,2 benzisothiazole (9).
The obtained zones of inhibition were
presented in table 1, which indicated that most of
the synthesized derivatives have moderate to good
antimicrobial activities.
Also the behavior of compound (9) towards
carbon nucleophiles (Grignard reagent) was
investigated. Thus when compound (9) submitted
REFERENCES
1.
2.
MagidAbou-Gharbia, John A.Moyer,
UshaPatel, Micheal Webb, Guy Schiehser,
Terrance Andree and J. Thomas Haskins, J.
Med Chem.,1989,32, 1024
Richard Poul Dunlap, Neil Warren, Albert
Mura and Dennis John Hlasta, (Sterling
Drug, Inc.), PCT Int. Appl.,1990,549,15.US
Appl.1989,347, 125,111pp.
Soon Kyoung Kwon and Myoung Suk, Arch.
Pharmacal Res.1992,15, 251-255
Donald Josef Dumas, EP 165003 A2US 85-72
6452, 1985, Appl, 111pp.
M.M.H.Arrief, M.S Amine and A.M.F Eissa,
Egypt. J.Chem.,1999,42(6), 563-571
“M.S. Amine and M.M.H.Arief, Indian
J.Chem.,1998,37,135-138
M.M.H Arief, S.G Donia, M.H.Azab and M.G
Zinhong, Egypt,J.Chem,1998,41(1-6), 257-
266
8.
M.M.H.Arief, Phosphorous, Sulfur, and
Silicon,1997,127, 159-165.
M.M.H.Arief, Phosphorous, Sulfur, and
Silicon,1996,114, 129-134.
A.A Failli, Us 4859671, 1989, Chem,
Abst,1990,112,7717.
D.J. Hlasta, R.C.Desai, C.Subramanyam,
E.P.lodge, R.P.Dunlap, N.W.Boaz, A.J.Mura,
and l.H.latimer, Eur.Pat.Appl.EP542372A1,
1993, Chem. Abst.1994,120(15), 191707,.
W.C.Groutas,N.Houser–Archield,l.S.Chong,
R.Venkataraman, J.B.Epp, H.Hunag and J.J.
McClenahan, J.Med.Chem.1993,36,3178-
81, Chem. Abst.1993,119,225875
N-Terzioglu, A.Gursoy, Eur.J.Med.
Chem,2003,38,781
9.
10.
11.
3.
4.
5.
6.
7.
12.
13.
14.
G.Kolavi, V.Hegde, I.Khan, P.Gaded, Bioorg.

ABDEllATTIF, Orient. J. Chem., Vol. 32(1), 567-574 (2016)
574
Med.Chem.2006,14, 3069.
A.K.Gaded, C.S.Mohajanshetti, S.NimalKar,
Eur.J.Med.Chem,2000,35, 853
M.Kidwai, P.Mothsra, Tetrahedron
Lett.2006,47, 5029
24.
25.
Atlas RM.Handbook of MicrobiologicalMedia.
london: CRC Press 2004,1226
Villanova PA. National Committee for Clinical
laboratory Standards (NCClS)Approved
standard document M-7A,1985
15.
16.
17.
18.
C.S. Andotra, T.C. langer, A. Kotha, J. Indian
Chem. Soc.
S.A. Siddiqui, Tetrahedron Lett,2005,61,
3539
H.C. Kan, Tetrahedron Lett.2007,63, 1644
D. luca, l.Curr, J. Med. Chem,2006, 13, 1
Adel A.H. Abdel-Rahman, shafey G. Donia,
A.A.F.Wasfy, A.A.Aly and AmaalY.El-Gazzar,
Der Pharma Chemica,2013, 5(1),196-204
R. Cruickshank, J.P. Dugui, B.P. Marion,
R.H.A Swain, Medicinal Microbiology 12thEdn.
Churchill london,(1975),196.
26.
Sandven P, lassen. Importance of Selective
Media for Recovery of Yeasts from
Clinical Specimens. J. Journal of clinical
microbiology,1999, 37(11),3731–3732
Magda H.Abdellattif, Mai.M.Helmy, Hany A.
Eldeab, IJAPBC – 2014,3(4),
Rishiramparajuli, janmajoybanerjee,
and hemantakhanal.oriental journal of
chemistry,2015,31,(4).2099-2106
Reza moradivalikboni, zabialahheidarnezha
d,fatemehheidarnezhad, yuldashboyhozhib
oevandrahmanrahmanov,oriental journal of
chemistry,2014, 30(1),391-394.
ChalakAzimi, Farhad Sepehraddin and
HelalTahazadeh, ORIENTAl journal of
chemistry,2013,29(4),1443-1448.
19.
20.
21.
27.
28.
22.
23.
29.
30.
Murray PR, Baron EJ, Pfaller MA,TenoverFC,
Yolken RH. Am. Soc. Micobiol.,Washington
D.C. 1995