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Paper Title:
Synthesis , Characterization and Antimicrobial, Antibacterial Activity
Evaluation of Some New Schiff Bases Derivative Thiocarbohydrazide
Ahmood KH. Jebur, Hiba Hamza Rasheed, Dardaa Aziz Ibrahim
Tikrit University - College of Sciences
A R T I C L E I N F O
Article history:
Received in 2019
Received in revised form 28/12/2019
Accepted 28/12/2019
Keywords:
Thiocarbohydrazide,
Anti-fungal ,
Anti-bacterial,
Schiff base ,
Triazole,
A B S T R A C T
Thiocarbohydrazide (H1) was synthesized by reaction of hydrazine with carbon disulfide CS2 , in the
presence of H2O with subsequent heating to remove H2S, N, N-dithiocarbohydrazone(H2) have been
synthesized from thiocarbohydrazide by reaction with Acetophenone and the later one was underwent the compound (H2) cyclization reaction by ferric chloride as a selective catalyst .to give 5-hydrazineyl-2-
methyl-2-phenyl-2, 3-dihydro-1, 3, 4-thiadiazole[H3]. The compound (H4) 2-mercapto-5- (4-amino
phenyl)-4, 3, 1-triazole was prepared by reaction between the p-amino carboxylic acid and the
thiocarbohydrazide. A series of 4-[4-(benzylidene amino-5-mercapto-4H-[1, 2, 4]triazol-3-yl]-aniline were
synthesized from 4-(4-amino-5-mercapto-4H-[1, 2, 4]triazol-3-yl)-aniline by reaction with different
aromatic aldehydes. The title compounds were evaluated for antibacterial activity against Gram-positive
bacteria (Staphylococcus aureus ) and Gram-negative bacteria (Escherichia coli) and anti-fungal activity against (Candida albicans ) , (Candida tropicalis). The synthesized thiocarbohydrazide derivatives and
Schiff base derivatives were characterized by both physical and spectral data like 1H-NMR, FT-IR. All
the synthesized were characterizing new derivatives by using analytical techniques (FT-IR and 1H NMR ,
as well as by using (C.H.N.S) measurements for these compounds.
© 2020. All rights reserved for Government University of UK.
Introduction
Thiocarbohydrazide(1-5)
is the closest structural analogue of thiosemicarbazide,
derivatives of which are recommended as effective anti-tubercular and antiviral preparations.
Thiocarbohydrazides of the aromatic series exhibit high antiviral and antimicrobial activity (6-
7).Thiocarbohydrazide are hydrazine derivatives of carbonic and thiocarbonic acids.
Thiocarbohydrazides are an important class of compounds which possess applications in both synthetic
organic chemistry and biological fields and has considerable value in many useful applications such as
synthesis of transition metal complexes(8, 9)
and pharmacological studies. Moreover, carbohydrazide
derivatives were widely used as an oxygen scavenger (metal passivation) for water treatment systems,
particularly for boiler-feed systems. To synthesis these active types of heterocyclic compounds , it
must be starting from active materials with wide biological applications, here in this presentation the
active starting material is thiocarbohydrazide [H1] which have best role in heterocyclic synthesis(10)
.
The chemistry of carbohydrazides has grown fast, and has not been reviewed in more than three
-
decades. Accordingly, it is important to shed more light on the recent literature dealing with that
chemistry, especially in the field of heterocycles. On the other hand, Thiocarbohydrazides are used in
performing a highly selective heavy metal ion adsorbent and as complexing agents for the solvent
extraction separation methods. Thiocarbohydrazide showed structural reinforcement effect in the
preparation of rabbit knee articular cartilage for the scanning electron microscope by enhancing the
binding of osmium tetroxide to it, possibly along with that of other soluble tissue constituents(11)
. Also
effective anti-tubercular.(12)
and antiviral preparations.(13)
exhibit high antiviral(14)
and antimicrobial
activity.(15)
effective fungi static agents, (16)
cytotoxicity of the well-known product melphalan.(17)
Scheme(1): synthesis of Thiocarbohydrazide, hydrazones , triazoles
Experimental Section
MATERIALS AND METHODS
All the chemicals used were supplied by Merck, BDH and Fluka chemicals. FTIR spectra were
recorded on SHIMADZU – FTIR 8400 Fourier transform infrared spectrophotometer using KBr discs.
Melting point were determined in open capillaries on Thomas Hoover apparatus and were uncorrected
.Finally, used C.H.N.S measurements .
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217
Synthesis Methods:
General Procedure for Synthesis of Thiocarbohydrazide.H1 (18-21)
In a 250 ml round bottomed flask equipped with a magnetic bar stirrer and dropping funnel, a solution
of carbon disulphide (CS2), (13ml, 0.22mol) under stirring to a mixture reaction of hydrazine
hydrate(24ml)and water (15ml), then stirring was continued for 30min at room temperature. The
reaction mixture temperature was then rapidly raised to 100-110oC. and after completion the addition,
the mixture was heated under reflux for 3hrs.on hot plate. The completion of the reaction was
confirmed by TLC, the reaction mixture was cooled and poured in the ice cold water ; the precipitate
was filtered and washed with water, followed by ether and then air dried. the product thus obtained
was recrystallized from water .Yield 80%, m.p.172 -173°C. 1H NMR (CDCl3, δ ppm):
1H-NMR
spectrum of this compound showed signals at δ= 4.49 (NH2) proton and a clear signal at δ= 8.60 ppm
due to (N-H). FT- IR(cm-1
): NH2 (3305), NH (3276, 3205) and C=S (1286).
Synthesis of 5-Aminophenyl-4H-1, 2, 4-triazol-3-yl)thiol H2 (22, 23)
In a 250 ml round bottomed flask equipped with a magnetic bar stirrer dissolve (0.02 mol, 2.4g)
acetophenone, then add (0.02 mol, 2.21g) of thiocarbohydrazide in 20 ml of hydrochloric acid (1N)
and stirring at room temperature for 1hr.The reaction mixture was then poured in ice cold water and
the resulting yellow precipitant solid was washed with water, dried and recrystallized from aq. ethanol,
m.p = 198-200 oC ; yield 85% .
1H NMR (CDCl3, δ ppm): δ (3.8 - 4.2) (s, 2H, NH2), δ 8.9 (s, 1H, NH),
δ (6.9-8.1) (m, 5H, aromatic C-H), δ 8.45 (s, 1H, N=CH). δ 2.15 (s, 3H, CH3). FT- IR (cm-1
): 3323,
3240 (NH2) 3335 (NH), 3012 (ArCH), 1229 (C=S), 1615 (C=N) .
Synthesis of 5-hydrazineyl-2-methyl-2-phenyl-2, 3-dihydro-1, 3, 4-thiadiazole [H3] ( 24)
:
The hydrazone [H2] (0.017 mole, 3.54 g) and FeCl3 (0.005 mole, 1.135 g) were dissolved in absolute
ethanol (25 ml), then the mixture was heated under reflux for (3hrs) in water bath. After completion of
reaction, the reaction mixture was cooled and poured in the ice cold water. The resulting solid was
dried and recrystallized from ethanol. m.p .(113-115 °C) ; Yield 60%; 1H NMR (CDCl3, δ ppm): δ 4.1
(s, 2H, NH2) , δ8.65(s, 1H, NH), δ7.2-7.65(m, 5H, aromaticC-H); FT- IR(cm-1
): 3320, 3240 (NH2)
3330 (NH), 3050 (Ar-CH), 756 (C-S-C), 1610 (C=N).
Synthesis of 4-(4-Amino-5-mercapto-4H-[1, 2, 4] triazol-3-yl)-benzoic acid (H4)(25)
A mixture of thiocarbohydrazide (H1) (0.015 mol) and p-amino benzoic acid (0.01 mol) were taken in a
round bottomed flask. The completion of the reaction was confirmed by TLC. The reaction mixture was
cooled; the precipitate was filtered and washed with water. The product was recrystallized from aq.
ethanol .Yield 80%, m.p. 150 - 153°C.
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Synthesis of 4-[4-(arylidene amino-5-mercapto-4H-[1, 2, 4] triazol-3-yl]-sub. benzoic acid H5(a-h)
Suspension of 4-(4-amino-5-mercapto-4H-[1, 2, 4] triazol-3-yl)-benzoic acid (H4) (0.2 mol) with
substituted benzaldehyde were placed in a 500 ml RBF, with 3 to 4 drops of Sulphuric acid was added.
The reaction mixture was refluxed for 2-3h. The reaction mixture was cooled; precipitate was filtered
and washed with water. The product was recrystallized with ethanol. Various substituted aldehyde used
in the reaction are mentioned in table (1)
Synthesis of 4-[4-(arylidene amino-5-mercapto-4H-[1, 2, 4] triazol-3-yl]benzoic acid 5(a)
81% yields as reddish solid; m.p.: 181-183oC;IR (KBr, cm
-1) νmax :3245(O-H str), 1025 (C-S),
1715(C=O str in COOH), 1595 (CH=N), 2921(C-H str); 1H-NMR (400 MHz, DMSO-d6, ppm), δ
(ppm): 13.84(s, 1H, OH), 9.75 (s, 1H, CH=N), 9.65 (s, 1H, C-SH), 7.85-6.85 (m, 9H, Ar-H);
Synthesis of 4-{5-Mercapto-4-[(4-methoxybezylidene)-amino]-4H-[1, 2, 4]-triazol-3-yl-}-benzoic
acid 5(b)
Yield (85%); m. p. 235-237ᵒC; FT-IR (KBr, λmaxcm-1
): 3025(C-H), 2848(OCH3), 1580(CH=N),
960 (C-S), 745 (C-H bend); 1H-NMR (400 MHz, DMSO-d6), δ (ppm), : 9.65 (s, 1H, C-SH), 9.40
(s, 1H, CH=N), 7.80-6.95 (m, 8H, Ar-H), 3.80 (s, 3H, OCH3) .
Synthesis of 4-{5-Mercapto-4-[(3-methyl-bezylidene)-amino]-4H-[1, 2, 4]triazol-3-yl}-benzoic acid
5(c)
Yield(76 %); m. p.245- 248ᵒC; FT-IR (KBr, λmaxcm-1
): 3035 (C-H str), 1583 (CH=N) , 942 (C-S);1H-
NMR (400 MHz, DMSO-d6), δ (ppm), 10.20 (s, 1H, CH=N), 7.85-7.35 (m, 8H, Ar-H), 2.42 (s, 1H,
CH3).
Synthesis of 4-{4-[(4-Bromo-benzylidene)-amino]-5-mercapto-4H-[1, 2, 4] triazol-3-yl}-benzoic
acid 5(d)
Yield (86%); m. p. 254- 256ᵒC; FT-IR (KBr, λmaxcm-1
): 3430(O-H str), 3030(C-H Ar str),
1630(C=C), 1596(CH=N), 965(C-S), 845(C-Br); 1H-NMR (400 MHz, DMSO-d6), δ (ppm),
9.90(s, 1H, C-SH), 7.70-7.30(m, 8H, Ar-H);
Synthesis of 4-{5-Mercapto-4-[(4-N, Ndimethyl-benzylidene)-amino]-4H-[1, 2, 4]triazol-3-yl}-
benzoic acid 5(e)
Yield (75%); m. p. 214-216ᵒC; FT-IR (KBr, , λmaxcm-1
): 3035(C-H Ar str), 2772(C-H str.),
1716(C=O str), 1572(CH=N), 1533(C=C) ; 1H-NMR (400 MHz, DMSO-d6), δ (ppm) 10.15 (s, 1H,
C-SH), 11.2 (1H, -NH), 8.2 CH=N), 8.42-7.50 (m, 8H, Ar-H); 2.38 (s, 6H, CH3).
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Table 1:Physical Properties of the compounds (H5a-e)
Comp.
No. R
Molecular
formula Colour Recrys .sol. M.P(0C)
Percentage
Yield (%)
H5a H C15H13N5S White EtOH 183 - 181 81
H5b OMe C16H15N5OS brown Acetonitrile 235-237 75
H5c CH3 C16H15N5S milky Chloroform 245- 248 86
H5d Br C15H12BrN5S White ACOH 254- 256 76
H5e NMe2 C17H18N6S Dark orange EtOH 214-216 85
RESULTS AND DISCUSSION
The structure of the compounds were confirmed from its melting point in Table (1) and (C.H.N.S)
analysis for some of them in Table (2). Besides FT-IR. Initially(26)
.Thiocarbohydrazide [H1]was
synthesis by reaction of hydrazine with CS2 in aqueous media through direct nucleophilic addition
reaction. Compound [H1] characterized by spectral methods represented by melting point , FT-IR and
1H-NMR, as shown in experimental section. The hydrazone compound [H2]Prepared by condensation
reaction with Acetophenone. This reaction was activated by few drops of (1N) hydrochloric acid, as
shown in (Scheme 2).
-
The compound (H3) was prepared by aqueous ferric chloride form 2-hydrazino-5-phenyl-5-acetyl.
(H2) . as in the following (scheme).
A novel series of 4-[4-(Arylidene amino-5-mercapto-4H-[1, 2, 4] triazol-3-yl]-benzoic acid complexes
from p-amino benzoic acid and thiocarbohydrazide was synthesized and characterized using analytical
methods like TLC, 1HNMR and FT-IR. The structures of newly synthesized compounds were
characterized on the basis of spectral data and elemental analysis. The physicochemical factors of the
above-synthesized compounds were mentioned in table (1).
The 1H-NMR spectrum of compounds [H5(a-d)] showed signals at δ= (3.50) ppm due to (NH2) group .
A multiple peak was observed on ν scale between 7.85-6.85ppm which showed the presence of the
aromatic ring in compound 5(a-h). Observation of singlet peak on ν scale between 9.75 -9.70 ppm
confirmed the presence of C-SH group in the compounds. The singlet also appeared at d 8.75- 9.75
ppm attributed to one proton of N=CH. Thus, it confirmed the formation of Schiff bases. in addition to
the above analysis of elements as in table 2.
The infrared FT-IR of the synthesized compounds[H5(a-d)] show The spectrum of compounds
appearance of reaction of compound (H4) with carbonyl compound product Schiff bases hydrazones
(H5a-d) showed strong band in the region (1615-1645) cm-1
as due to CH = N stretching vibration, and
disappeared bonds at (3290 and 3210) cm-1
of a symmetric and symmetric N-H stretching. and this is
an excellent proof for the success of hydrazone compounds formation and appearance of the absorption
band of –SH (2600- 2400 cm-1
) .
Analysis of Elements(C.H.N.S)
The physical properties appearance of the synthesized , melting point, Yield% , Molecular formula ,
Recrystallization solution are listed in table (1). The CHNS measurements of compounds that prepared
are refer to correct suggested structure of this research compounds. The elements values are listed in
table (2 ).
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Table 2: Elemental analysis ( C.H.N.S) of compounds (H5a-d)
Comp. No.
C % H % N % S %
Cal. Found Cal. Found Cal. Found Cal. Found
H5a 61.71 58.360 4.31 3.810 22.91 23.16 10.57 10.310
H5b 62.68 61.383 4.51 3.364 22.88 23.04 10.32 9.95
H5c 59.27 58.854 4.79 3.975 21.83 22.03 9.90 10.10
H5d 48.84 47.966 3.22 3.922 18.83 19.036 8. 81 7.67
H5e 60.32 60.531 5, 47 5.76 24.54 24.659 9.79 8.580
Anti-microbial activity.
All the newly synthesized titled compounds H5(a-e) were tested for anti-microbial activities by using the
disc diffusion method, (27-29)
.The compound 5(a-h) were assessed against Gram-positive
(Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli) and antifungal activity against
Candida albicans, Candida tropicalis, Streptomycin and Griseofulvin were used as a standard .
It was found that the compounds containing the bromo group, methyl , N, N-dimethyl and methoxy
substitution along with the Schiff bases systems. exhibited significant antimicrobial, antifungal
activity. Whereas, other derivatives containing other groups like methyl , methoxy and N, N-di methyl
group showed moderate to weak anti-microbial activity. It was found that of newly Schiff base
derivatives Compounds H5b, H5c , H 5(d) and H5(e), showed significant activity against Gram-
positive (Staphylococcus aureus whereas compounds H5b, H5d, and H5e showed significant
antifungal activity against Candida albicans and Candida tropicalis. While H5(d), H5(b) showed
moderate activity against bacterial strains. Anti-microbial data of all the synthesized compounds were
shown in table (3). The presence of bromine atom at para position in H5(d) has increased the
antimicrobial activity of the compound H5b. The similarly presence of methoxy group at para position
increased the antibacterial activity of H5(c), whereas, the remarkable antifungal activity of H5(e)
observed due to the presence of substituted amino group at para position. Similarly, the good anti-
bacterial activity of H5(d) was also reported due to the presence of Chloro group at para position
compound H5d. Antimicrobial activity depends on the nature of bacterial strain, the solvent and
chelating ability of the Schiff base. It is believed that Schiff bases act by forming a chelate with the
bacterial strain , Electron withdrawing ability of bromine yielded a compound with significant anti-
bacterial activity, as shown in the pictures in the below.
-
CONCLUSION
In conclusion, the synthesis of the Schiff base compounds Substituted thiocarbohydrate derivatives
(H5a-d) by using thiocarbohydrazide, p-amino benzoic acid and substituted aromatic aldehydes in
presence of ethanol. All the derivatives prepared by this method are analyzed by 1HNMR and IR. The
title compounds were evaluated for antibacterial activity against Gram-positive bacteria
(Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli) While, anti-fungal activity
against (Candida albicans) and. (Candida tropicalis). As in table (3, 4). Results revealed that the
compound H5b showed very good antibacterial activity while, H5c and H5d, H5e, showed good
antibacterial activity. On the other hand antifungal activity against (Candida albicans) and. (Candida
tropicalis). Results revealed that the compounds H5c , H5d, H5e showed very good antifungal activity
.The study would be a fruitful matrix for the development of Substituted thiocarbohydrate derivatives
for further bio-evaluation. From the results of various biological activities it is clear that these
compounds would be of better use in drug development.
Table 3. Antifungal , Antibacterial activity of synthesis N, N-dithiocarbohydrazone derivatives
compounds Conc.
in µg/mL
Zone of inhibition in (mm) Zone of inhibition in (mm)
Staphylococcus
aureus
Escherichia
colis
Candida
tropicalis
Candida
tropicalis
H5a
A 0.010 22 16
A 0.050 22 14 16 71
A 0.0150 19 14 14 71
H5b
A6 0.010 34 13 18 71
A60.050 30 11 20 13
A60.0150 32 11 16 71
H5c
A9 0.010 21 14 21 71
A90.050 20 13 16 02
A9 0.0150 20 14 17 14
H5d
B7 0.010 25 16 19 18
B70.050 19 17 16 15
B70.0150 20 18 17 18
H5e
D30.010 20 16 19 19
H3 0.050 13 13 16 15
K5 0.0150 20 14 18 16
Streptomycin std. - 02 02 15 18
Griseofulvin std. - 01 01
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الفعالية التثبيطية للمركب (H4a) Staphylococcus aurea
الفعالية التثبيطية للمركب(H5b ) Staphylococcus aurea
الفعالية التثبيطية للمركب(H5c ) Staphylococcus aurea
الفعالية التثبيطية للمركب(H5d ) Staphylococcus aurea
لفعالية التثبيطية للمركب (H5a ) Esheriechia coli
لفعالية التثبيطية للمركب (H5b ) Esheriechia coli
لفعالية التثبيطية للمركب (H5c ) Esheriechia coli
لفعالية التثبيطية للمركب(H5d ) Esheriechia coli
-
لفعالية التثبيطية للمركب
(H5e ) Esheriechia coli
( H5a) الفعالية التثبيطية للمركباتCandida albicans
( H5b) الفعالية التثبيطية للمركباتCandida albicans
( H5c) الفعالية التثبيطية للمركباتCandida albicans
( H5d) الفعالية التثبيطية للمركباتCandida albicans s
( H5e) الفعالية التثبيطية للمركباتCandida albicans
References
1- Loudon GM. ‘Organi Chemistry’, Addition-Weseley, Califomia, 2002, Ed.4th, p. 874 .
2- Aly AB, Brown El-Emary, Ashraf M, Mohamed E and Mohamed Ramadan. ARKIVOC 9002 ( .150-197.
3- Sun X, H Liu YF. Huaxue Tongbao 1999, 62, 46-48.
4- Islam MR, Khayer K, Shaha G, Chowdhury MSK. India J Chem 1992; 31B, 547.
5- Sathisha MP, Ullas N, Shetti VK, Revankar KS. European J Med Chem 2008; 43: 2338 9432 –
6- Marina K, Anastssia M, Panagiotis M, Nicole P, Spyroula PG, Christophe P, Myriam W, Erik DC. Farmaco 2002;
57: 253-257.
7- Holla BS, Akberali PM, Shivananda MK. Farmaco 2001; 56: 919-927.
8- Mikhailov, O. V.; Kazymova, M. A.; Shumilova, T. A.; Chmutova, G. A.; Solovieva, S. E. Transition Met. Chem.
2005, 30, 299.
9- Saha, G. C.; Khayer, K.; Islam, M. R.; Chowdhury, M. S. K. Indian J. Chem. 1992, 31B, 547.
10- Slovinsky, M. (Nalco Chemical Co.) U. S. Pat. 1980, 4, 269, 717; Chem.
11- Donovick, R.; Pansy, F.; Stryker, G.; Bernstein, J. J. 40 Bacteriol. 1950, 59, 667.
12- Popat, K. H.; Purohit, D. H.; Chovatia, P. T.; Joshi, H. S. J. Indian Chem. Soc. 2005, 82, 940.
-
Vol 12, No 27: Dec 2019 (Part I)
225
13- Genova, P.; Varadinova, T.; Matesanz, A. I.; Marinova, D.; Souza, P. Toxicol. Appl. Pharmacol. 2004, 197, 107.
14- Blumenkopf, T. A.; Harrington, J. A.; Koble, C. S.; Bankston, D. D.; Morrison, R. W., Jr.;Bigham, E. C.; Styles,
V. L.; Spector, T. J. Med. Chem. 1992, 35, 2306.
15- Abu-Hussen, A. A. A.; Emara, A. A. A. J. Coord. Chem. 2004, 57, 973.
16- Naik, A. D.; Annigeri, S. M.; Gangadharmath, U. B.; Revankar, V. K.; Mahale, V. B. J.Inclusion Phenom.
Macrocycl. Chem. 2002, 43, 291.
17- Dimmock, J. R..; Kumar, P.; Allen, T. M.; Kao, G. Y.; Halleran, S.; Balzarini, J.; De Clercq, E. Pharmazie 1997,
52, 182.
18- Gupta AK, Prachand S, Patel A, Jain S. Synthesis of some 4-amino-5-(substituted-phenyl)-4H-[1, 2, 4] triazole-3-
thiol derivatives and antifungal activity. Int J Pharm Life Sci 2012;3:1849-57
19- Holla BS, Akberali PM, Shivananda MK. Farmaco 2001; 56: 919-927.
[11] Hui XP, Zhang Y, Xu PF, Wang Q, Zhang Q, Zhang ZY. Chin J Org Chem 2005; 25: 700-704.
20- Nagaraja Reddy, Prakash G, Prema A, Badami S and Patih SA. J Saudi Chem Soc 2007;11 No.2: 253-268.
21- Zhou J, Wu D, Gou J (2010) Optimization of the production of thiocarbohydrazide using the Taguchi method. Chem
Technol Biotechnol 85:1402–1406.
22- Patil.C B., Mahajan.S.K., Katti.S.A. (2009). Chalcone: A Versatile Molecule, J.Pharm.Sci, 3, 11- 22.
23- Mohamed A, Badawy A, Sayed A, Hady A (1991) Reaction of isatin with thiocarbohydrazide: a correction. Arch
Pharm (Weinheim) 324:349–351.
24- Rajin M., Devinder K., Satbirm. (2014). Synthesis and Antimicrobial Activity of Some 1, 3‐Disubstituted Indeno[1, 2‐
c]pyrazoles, J.Heterocyclic Chem, 51, 203 .
25- SHARMA V., KUMAR M. D, DAS R. KAWAL K. P. (2016). synthesis of some novel triazole derivatives as Schiff
bases and their antimicrobial evaluation International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-
1491 Vol 8, Issue 9.
26- Shaymaa K.Y. Aemn Y.S. Synthesis a Series of 2-Pyrazolideno-1, 3, 4-Thiadiazoline Compounds Derived from
Thiocarbohydrazide.The Eurasia Proceedings of Science, Technology, Engineering & Mathematics (EPSTEM), 2019
.Volume 7, Pages 141-146.
27- Mehta D, Das R, Dua K. Synthesis, anti-inflammatory and antimicrobial activity of some new 1, 3, 4-oxadiazoles
and 1, 3, 4-oxadiazoles-2-thione derivatives as mannich bases containing furan moiety. Int J Chem Sci 2009;2:225-34.
28- Benson, H. J. Microbiological Applications, W M C Brown Publications, USA, 1990.
29- Colle, J. G.; Duguid, J. P.; Fraser, A. G.; Mammion, B. P. Mackie and McCartney Practical Medical Microbiology,
Churchil, Livingston Ltd, London, 13th ed.1989.
The acceptance letter # was: CAAU-12-27-Sci.