Amino acids in the syntheses of heterocyclic systems: Syntheses and radiostability of novel biologically active triazoles containing the sulfonamide moiety

Article abstract of DOI:10.1002/hc.10037

A number of novel triazoles 2a-f, 4, 9, 10, 12, 15; triazolothiadiazoles 6, 8, 11, 16; triazolothiadizine 5; and triazolotriazine 14 were synthesized and characterized by elemental analyses and spectral data. Six of the compounds showed antifungal activity compared with the fungicide Mycostatine. Radiosterilization of the biologically active compounds 4, 8, 9b, and 10 in the dry state may prove to be applicable at the sterile dose 25 kGy.

Full text of DOI:10.1002/hc.10037

Heteroatom Chemistry
Volume 13, Number 4, 2002
Amino Acids in the Syntheses of Heterocyclic
Systems: Syntheses and Radiostability
of Novel Biologically Active Triazoles
Containing the Sulfonamide Moiety
A. M. Sh. El-Sharief,1 M. M. Ghorab,2 M. S. A. El-Gaby,3
Sh. I. Mohamed,1 and Y. A. Ammar1
1Department of Chemistry, Faculty of Science, Al-Azhar University, Nasr City, P.O. Box 11884,
Cairo, Egypt
2Department of Drug Radiation Research, National Center for Radiation Research and Technology,
P.O. Box 29, Nasr City, Cairo, Egypt
3Department of Chemistry, Faculty of Science, Al-Azhar University, Assiut 71524, Egypt
Received 7 August 2001; revised 11 September 2001
rating the above mentioned biologically active moi-
ABSTRACT: A number of novel triazoles 2a–f, 4, 9,
eties in one molecule and evaluated their antifungal
10, 12, 15; triazolothiadiazoles 6, 8, 11, 16; triazoloth-
activity. The application of radiation in pharmaceu-
iadiazine 5; and triazolotriazine 14 were synthesized
ticals technology has steadily increased during the
and characterized by elemental analyses and spectral
past few years [10,11]. In the 1997 edition of the
data. Six of the compounds showed antifungal activ-
European pharmacopoeia, under the methods of
ity compared with the fungicide Mycostatine. Radios-
preparation of sterile products, irradiation is one
terilization of the biologically active compounds 4, 8,
of only three processes that can be used as a ter-
9b, and 10 in the dry state may prove to be applica-
minal sterilization method. Also, considerable inter-
C
ble at the sterile dose 25 kGy. 2002 Wiley Periodicals,
est has developed regarding the radiation sensitivity
Inc. Heteroatom Chem 13:316–323, 2002; Published on-
of various antibiotics [12,13] and recently synthe-
line in Wiley Interscience (www.interscience.wiley.com).
sized biologically active compounds [14,15]. Gener-
DOI 10.1002/hc.10037
ally, data of these compounds indicate that even at a
dose of 25 kGy the radiosterilization may be feasible
[16,17].
INTRODUCTION
The triazole ring system has important and versa-
CHEMISTRY
tile biological activities [1–5]. On the other hand,
Several compounds were designed with the aim of
triazolothiadiazole, thiadiazine, triazine, and sul-
exploring their antifungal activity (Schemes 1–4).
The starting materials 1a–f were prepared by re-
action of the appropriate sulfonyl chloride deriva-
tives with amino acids in the presence of sodium
fonamide derivatives are well known as antifungal
agents [6–9]. In view of these findings, we undertook
the synthesis of a new series of compounds incorpo-
hydroxide solution (10%), with subsequent acidi-
fication [18]. The s-triazolosulfonamide derivatives
2a–f were obtained in good yields by fusion of the
Correspondence to: A. M. Sh. El-Sharief; e-mail: ahmed shab@
hotmail.com
2002 Wiley Periodicals, Inc.
c
316

Amino Acids in the Syntheses of Heterocyclic Systems 317
SCHEME 1
respective compounds 1a–f with thiocarbohydrazide
in an oil bath at 180 C (Scheme 1).
derivative 4 was obtained (Scheme 2). The structure
of compound 4 was proved by elemental analyses,
IR, and 1H NMR spectroscopy. The IR spectrum
showed the absence of NH, NH2 of the triazole ring
The structures of compounds 2a–f were con-
firmed on the basis of elemental analyses and spec-
1
1
tral data. H NMR spectrum of 2a in DMSO-d6 ex-
and the presence of the SO2NH moiety at 3150 cm
1
hibited = 2.4 (s, 3H, CH3), 4.0 (d, 2H, CH2), 5.4 (s,
2H, NH2), 7.2–7.8 (m, 4H, Ar-H), 8.3 (br, 1H, SO2NH),
13.4 (s, 1H, NH). MS of 2a (m/z): 284 (M-15, 16.80%),
91 (100%), 149 (15.20%), 105 (13.50%), 59 (20.0%).
IR spectrum of 2b showed bands at 3390, 3330, 3200
(NH, NH2), 3100 (CH aromatic), 2970 (CH aliphatic),
and 3C O groups at 1716, 1690, 1670 cm . The
1H NMR spectrum of 4 in DMSO-d6 revealed
=
2.1 (s, 6H, N(COCH3)2), 2.2 (s, 3H, NCOCH3), 4.8
(s, 2H, CH2), 7.1–8.0 (m, 3H, Ar-H), 8.9 (s, 1H,
SO2NH). Reaction of 2d with ethyl chloroacetate fur-
nished the triazolothiadiazine derivative 5. MS (m/z):
395 (M+, 35.71%), 180 (100%), 355 (35.71%), 285
(64.29%), 220 (64.29%), 176 (39.29%), 118 (32.14%),
94 (39.29%), 78 (3.57%). Also, reaction of 2d with
benzoyl chloride in pyridine effected cyclization to
furnish triazolothiadiazole 6, rather than the ben-
zoylaminotriazole derivative 7, based on the elemen-
tal analyses and IR spectrum, which showed the ab-
sence of a C O band and the presence of an NH
band at 3460, a CH aliphatic group at 2910, and a
1
1650 (C N), 1320 (C S). H NMR spectrum of 2b
in DMSO-d6 exhibited = 1.3 (d, 3H, CH3), 2.3 (s,
3H, CH3 tolyl), 4.5 (q, 1H, CH), 5.4 (s, 2H, NH2),
7.2–7.8 (m, 4H, Ar-H), 8.6 (br, 1H, SO2NH), 13.4 (s,
1H, NH). IR spectrum of 2d showed bands at 3400,
3300, 3150 (NH, NH2), 3100 (CH aromatic.), 2900
1
(CH aliphatic), 1590 (C N). H NMR spectrum of
2d in DMSO-d6 exhibited = 4.2 (d, 2H, CH2), 5.5 (s,
2H, NH2), 7.6–8.0 (m, 3H, Ar-H), 8.8 (s, 1H, SO2NH),
13.6 (s, 1H, NH). MS of 2d (m/z): 353 (M+, 38.2%),
145 (100%), 209 (34.0%), 163 (17.0%), 144 (72.20),
73 (32.70%), 60 (52.80%). IR spectrum of 2e showed
bands at 3350, 3300, 3200 (NH, NH2), 3100 (CH aro-
matic.), 2950 (CH aliphatic), 1620 (C N). MS of 2f
(m/z): 363 (M+, 27.20%), 144 (100%), 219 (10.30%),
158 (3.90%), 74 (9.60%).
1
C N group at 1610 cm . MS of 6 (m/z): 439 (M+,
1.52%), 73 (100%), 355 (4.66 %), 275 (10.18%), 207
(46.43%), 150 (30.35%), 107 (24.64%), 60 (68.13%).
The triazolothiadiazole derivative 8 was ob-
tained in good yield by the reaction of 2d with
phenyl isothiocyanate in pyridine. The structure of
8 was established by elemental analyses and its IR
spectrum, which showed the absence of NH2 bands
The reaction of compound 2d with acetic anhy-
dride was carried out in a trial for obtaining tria-
zolothiadiazole derivative 3, but instead the triacetyl
1
and presence of NH at 3150 cm , and of C N at
1
1595 cm .

318 El-Sharief et al.
SCHEME 2
Condensation of 2d with aromatic aldehydes in
glacial acetic acid afforded Schiff bases 9a–c, while,
under condition of fusion, the reaction of 2d with
benzaldehyde caused cyclization to afford the corre-
sponding triazolothiadiazole derivative 6. The struc-
ture of 6 was also confirmed through its synthesis
by reaction of 9a with thionyl chloride (Scheme 3).
The1H NMR spectrum of 9b in DMSO-d6 revealed
= 3.8 (s, 3H, OCH3), 4.3 (s, 2H, CH2), 7.0–7.9 (m,
7H, Ar-H), 8.3 (s, 1H, SO2NH), 9.7 (s, 1H, N CH),
13.9 (s, 1H, NH).
The dicyano derivatives 10 and 11 were
obtained in good yields by reaction of com-
pound 2d with ethoxymethylenemalononitrile and
[bis(methylsulfanyl)methylidene]malononitrile, re-
spectively in dimethylformamide. The IR spectrum
of 10 showed bands at 3430 (NH), 2925 (CH
aliphatic), 2211 (C N), 1615 (C N). MS of 10
(m/z): 429 (M+, 0.67%), 55 (100%), 368 (4.88%), 327
(3.33%), 257 (8.86%), 152 (17.44%), 111 (41.07%),
73 (53.57%). The IR spectrum of 11 showed bands
at 3200 (NH), 3100 (CH aromatic.), 2927 (CH
SCHEME 3

Amino Acids in the Syntheses of Heterocyclic Systems 319
1
give the corresponding triazolothiadiazole 16. IR
spectrum of compound 15 exhibited bands at 3276
(NH), 3094 (CH aromatic.), 2942 (CH aliphatic),
aliphatic), 2210 (C N), 1620 cm (C N). MS of 11
(m/z): 427 (M+, 5.22%), 177 (100%), 386 (18.26%),
354 (36.09%), 284 (48.26%), 193 (37.39%), 148
(15.22%), 106 (80.43%), 62 (45.65%).
1
1640 (C O), 1590 (C N). The H NMR of 15 in
DMSO-d6 revealed = 4.6 (d, 2H, CH2), 7.2–8.0 (m,
8H, Ar-H), 9.0 (t, 1H, CONH), 10.1 (s, 1H, N CH),
14.0 (s, 1H, NH triazole). The 1H NMR of compound
16 in DMSO-d6 showed = 4.5 (d, 2H, CH2), 7.3–8.1
(m, 8H, Ar-H), 9.0 (t, 1H, CONH).
Fusion of each thiocarbohydrazide with 2-
chlorohippuric acid afforded the corresponding tria-
zole derivative 12, while, with 4-chlorohippuric acid,
double cyclization occurred to give the triazolotri-
azine 14 through the formation of the expected tri-
azole derivative 13 (Scheme 4). The structures of 12
and 14 were established by elemental analyses and
EXPERIMENTAL
1
by IR, H NMR, and MS spectroscopy. The IR spec-
All melting points are uncorrected and were deter-
mined on an electrothermal STUART melting point
apparatus (SCIENTIFIC Co. Ltd, UK). IR spectra
trum of 12 showed bands at 3328, 3250, 3182 (NH,
NH2), 3087 (CH aromatic.), 2947 (CH aliphatic),
1
1640 (C O), 1592 (C N). The H NMR spectrum
1
(cm ) were recorded on a Pye-Unicam spectropho-
of 12 in DMSO-d6 exhibited = 4.5 (d, 2H, CH2),
5.6 (s, 2H, NH2), 7.4–7.6 (m, 4H, Ar-H), 8.9 (t, 1H,
CONH), 9.0 (s, 1H, NH triazole). The IR spectrum of
14 showed the absence of (C O) and the presence of
NH at 3250, the CH aromatic at 3100, the C N group
tometer, type 1200, using the KBr technique. 1H
NMR spectra were recorded on a Varian EM-390
(90 MHz) spectrometer using TMS as an internal
standard, DMSO-d6 as a solvent and chemical shifts
were expressed in values. Mass spectra were run
using an HP Model: MS-5988 instrument. Elemental
analyses were determined using a Perkin-Elmer 240
(Microanalyses) instrument. The samples were irra-
diated with gamma radiation (60Co) at the National
Center for Radiation Research and Technology. Pow-
der samples contained in polycarbonate vials were
1
at 1620, 1595 cm . MS of 14 (m/z): 265 (M+, 0.1%),
131 (100%), 236 (0.7%), 192 (0.1%), 158 (0.31%), 116
(0.74%), 85 (7.76%), 60 (11.25%).
Condensation of 12 with 4-chlorobenzaldehyde
in acetic acid furnished the Schiff base 15, while,
under the conditions of fusion, the reaction of 12
with 4-chlorobenzaldehyde effected cyclization to
SCHEME 4

320 El-Sharief et al.
irradiated at room temperature. UV spectra were
recorded using a ATI Unicam UV–VIS Aurora Scan
instrument.
etate (1.22 g, 0.01 mol) was added. The reaction mix-
ture was refluxed for 2 h. The formed product was
filtered off, washed with water, dried and recrystal-
lized from ethanol to give 5.
General Procedure for Syntheses of Tosyl Amino
Acids (1a–f)
(6-Phenyl-s-triazolo[3,4-b][1,3,4]thiadiazol-3-yl)-
methyl-2,5-dichlorobenzenesulfonamide (6)
The tosyl amino acid derivatives were prepared
according to the procedure of McChesney et al.
[18], where each amino acid (0.026 mol) was dis-
solved in 1 N NaOH (25 ml) and in a period of 13
min a solution of p-toluenesulphonyl chloride or
2,5-dichlorophenylsulphonyl chloride or p-bromo-
phenylsulphonyl chloride (0.027 mol) in ether (30
ml) was added in portions. The mixture was stirred
at room temperature for 3 h. The excess sulphonyl
chloride was filtered off and the solution treated with
2 N HCl until acidic to congo red indicator (pH 5).
After cooling, acidification caused the product to pre-
cipitate. The crude product was filtered off, washed
with water, and dried. The crude materials were re-
crystallized to give 1a–f.
Method A: A solution of compound 2d (3.5 g, 0.01
mol) in dry pyridine (20 ml) and benzoyl chloride
(1.40 g, 0.01 mol) was added. The reaction mixture
was refluxed for 8 h. After cooling and acidification
with dil. HCl, the precipitate was formed and then
collected by filtration, washed with water, and re-
crystallized from dioxane to give 6.
Method B: A mixture of 2d (3.5 g, 0.01 mol) and
benzaldehyde (1.06 g, 0.01 mol) was fused for 15 min
at 220 C in an oil bath. After cooling, the reaction
mixture was triturated with ethanol to give 6.
Method C: A solution of 9a (4.41 g, 0.01 mol)
in thionyl chloride (10 ml) was refluxed for 1 h and
the obtained solid was recrystallized from dioxane
to give 6.
General Procedure for Syntheses
of s-Triazolosulfonamide Derivatives (2a–f)
(Anilino-s-triazolo[3,4-b][1,3,4]thiadiazol-3-yl)-
A mixture of thiocarbohydrazide (1.06 g, 0.01 mol)
and different sulfonyl amino acids 1a–f (0.01 mol)
were fused at 180 C in an oil bath for 15 min.
After cooling, each reaction mixture was triturated
with ethanol to give (4-amino-5-mercapto-s-triazol-
3-yl)-methyl-4-tolylsulfonamide (2a), (4-amino-5-
mercapto-s-triazol-3-yl)-methyl-ethyl-4-tolylsulfona-
mide (2b), (4-amino-5-mercapto-s-triazol-3-yl)-
methyl-isobutyl-4-tolylsulfonamide (2c),(4-amino-
5-mercapto-s-triazol-3-yl)-methyl-methyl-2,5-dichlo-
robenzenesulfonamide (2d), (4-amino-5-mercapto-
s-triazol-3-yl)-methyl-ethyl-2,5-dichlorobenzenesul-
fonamide (2e), and (4-amino-5-mercapto-s-triazol-
3-yl)-dimethyl-4-bromobenzenesulfonamide (2f).
methyl-2,5-dichlorobenzenesulfonamide (8)
A solution of 2d (3.5 g, 0.01 mol) and phenyl isothio-
cyanate (1.35 g, 0.01 mol) in dry pyridine (20 ml) was
refluxed until the evolution of H2S had ceased (12 h).
The reaction mixture was poured into ice-cold water
(100 ml). The precipitate was filtered off, dried and
recrystallized from ethanol to give 8.
(4-Arylideneamino-1H-5-thioxo-s-triazol-3-yl)-
methyl-2,5-dichlorobenzenesulfonamides (9a–c)
A mixture of 2d (3.5 g, 0.01 mol) and benzaldehyde or
4-methoxybenzaldehyde or 4-chlorobenzaldehyde in
acetic acid (10 ml) was refluxed for 5 h. The solvent
was evaporated under reduced pressure. The solid
product was collected and recrystallized from acetic
acid to give 9a–c.
(1-Acetyl-4-diacetylamino-5-thioxo-s-triazol-3-yl)-
methyl-2,5-dichlorobenzenesulfonamide (4)
A solution of 2d (3.5 g, 0.01 mol) in acetic anhydride
(20 ml) was heated under reflux for 10 h. After cool-
ing the excess of acetic anhydride was removed un-
der reduced pressure. The obtained solid was recrys-
tallized from acetic acid to give 4.
(4-Aminomethylenemalononitrile-1H-5-thioxo-
s-triazol-3-yl)methyl-2,5-dichlorobenzenesulfo-
namide (10) and (6-dicyanoethylidene-5H-s-
triazolo[3,4-b]thiadiazol-3-yl]methyl-2,5-
dichlorobenzenesulfonamide (11)
(6-Oxo-5H-s-triazolo[3,4-b][1,3,4]thiadiazin-3-yl)-
methyl-2,5-dichlorobenzenesulfonamide (5)
A mixture of 2d (3.5 g, 0.01 mol), ethoxymethylene-
malononitrile or [bis(methylsulphonyl)methylidine]
malononitrile (0.01 mol), and triethylamine (1.01 g,
0.01 mol) in dimethylformamide (20 ml) was
To a solution of 2d (3.5 g, 0.01 mol) in dioxane (50 ml)
and triethylamine (1.01 g, 0.01 mol), ethyl chloroac-

Amino Acids in the Syntheses of Heterocyclic Systems 321
TABLE 1 Characterization Data for Newly Synthesized Compounds
Elemental Analysis [Calculated/Found (%)]
Compound
M.P. ( C)
200–202
195–197
218–220
205–207
210–212
214–216
70–72
Yield (%)
80
Mol. Formula (Mol. Wt)
C10H13N5O2S2 (299)
C11H15N5O2S2 (313)
C13H19N5O2S2 (341)
C9H9N5O2S2Cl2 (353)
C9H10N5O2S2Br (363)
C10H11N5O2S2Cl2 (367)
C15H15N5O5S2Cl2 (479)
C11H9N5O3S2Cl2 (393)
C16H11N5O2S2Cl2 (439)
C16H12N6O2S2Cl2 (454)
C16H13N5O2S2Cl2 (441)
C17H15N5O3S2Cl2 (471)
C16H12N5O2S2Cl3 (475)
C13H9N7O2S2Cl2 (429)
C13H7N7O2S2Cl2 (427)
C10H10N5OSCl (283)
C10H8N5SCl (265)
C
H
N
2a
2b
2c
2d
2f
40.13
40.00
42.17
42.40
45.75
45.55
30.59
30.80
29.75
29.60
32.69
32.80
37.57
37.80
33.58
33.30
43.74
43.40
42.29
42.50
43.53
43.70
43.31
43.60
40.42
40.60
36.36
36.00
36.53
36.20
42.40
42.20
45.28
45.00
50.37
50.10
50.37
50.50
4.35
4.50
4.79
4.60
5.57
5.50
2.55
2.50
2.75
2.55
2.99
2.80
3.13
3.40
2.29
2.60
2.51
2.70
2.64
2.50
2.95
2.80
3.18
3.40
2.53
2.60
2.09
2.30
1.63
1.40
3.53
3.10
3.02
3.20
3.20
3.50
3.20
3.40
23.41
23.20
22.36
22.20
20.53
20.70
19.83
19.60
19.28
19.40
19.07
19.00
14.61
14.30
17.81
17.50
15.95
16.20
18.50
18.80
15.87
15.90
14.86
15.10
14.74
14.60
22.84
22.60
22.95
22.70
24.73
24.90
26.42
26.20
17.28
17.40
17.28
17.60
85
79
74
70
2e
4
76
75
5
150–152
>300
72
6
72
8
90–92
79
9a
9b
9c
10
11
12
13
15
16
260–262
180–182
290–292
155–157
120–122
210–212
205–207
253–255
280–282
79
82
88
83
81
70
78
76
C17H13N5OSCl2 (405)
C17H13N5OSCl2 (405)
56
[4-(40-Chlorobenzylideneamino)-1H-5-thioxo-s-
triazol-3-yl]methyl-2-chlorobenzenecarboxamide
(15)
refluxed for 10 h. The obtained solid was re-
crystallized from dioxane to give 10 and 11,
respectively.
A mixture of 12 (2.83 g, 0.01 mol) and 4-
chlorobenzaldehyde (1.40 g, 0.01 mol) in acetic acid
(20 ml) was refluxed for 4 h. The solvent was evapo-
rated under reduced pressure. The solid product was
recrystallized from acetic acid to give 15.
(4-Amino-5-mercapto-s-triazol-3-yl)methyl-2-
chlorobenzenecarboxamide (12) and 6-
(40-chlorophenyl)-1,4,7-trihydro-9-thioxo-s-
triazolo-[3,4-b][1,2,4]triazine (14)
A mixture of thiocarbohydrazide (1.06 g, 0.01 mol)
and 2-chlorohippuric acid or 4-chlorohippuric acid
(2.13 g, 0.01 mol) was fused at 180 C in an oil
bath for 15 min. After cooling, the reaction mixture
was triturated with ethanol and the obtained solid
was recrystallized from ethanol to give 12 and 14,
respectively.
[6-(4-Chlorophenyl)-s-triazolo[3,4-b][1,3,4]thia-
diazol-3-yl)methyl-2-chlorobenzenecarboxamide
(16)
A mixture of 12 (2.83 g, 0.01 mol) and 4-
chlorobenzaldehyde (1.40 g, 0.01 mol) was fused at

322 El-Sharief et al.
TABLE 2 Antifungal Activity of Some Newly Synthesized Compounds (Inhibition Zones, mm)
Aspergillus ochraceus
Wilhelm (AUCC-230)
Aspergillus flavus
Link (AUCC-164)
Penicillium chrysogenum
Thom (AUCC-530)
Candida albicans (Robin)
Berkho (AUCC-1720)
2a
2b
2c
2d
2f
4
18
24
22
20
34
32
40
24
40
34
40
18
24
20
22
36
34
40
22
40
32
40
20
24
20
20
40
40
40
34
35
30
42
10
24
18
20
40
40
34
35
34
24
40
6
8
9b
10
Mycostatinea
aManufactured by Bristol-Myers Squibb, Giza, Egypt.
220 C in an oil bath for 15 min. After cooling, the re-
action mixture was triturated with ethanol to give 16.
active compounds 4, 8, 9b, and 10 before steriliza-
tion. These compounds were irradiated in the dry
state (doses of gamma irradiation ranging from 5–
40 kGy) at dose rate 1 kGy/7 min. Ultraviolet spectra
ANTIFUNGAL ACTIVITY
TABLE 3 UV Spectra of Biologically Active Compounds 4,
Most of the newly synthesized compounds were
screened for their antifungal activity against four
species of fungi, namely Aspergillus ochraceus Wil-
helm (AUCC-230), Aspergillus flavus Link (AUCC-
164); Penicillium chrysogenum Thom (AUCC-530),
and Candida albicans (Robin) Berkho (AUCC-1720),
using a cup plate agar diffusion method [19]. The
fungi cultures were maintained on Czapek’s Dox agar
medium. The tested compounds were dissolved in
N,N-dimethylformamide (DMF) to get a solution of
1 mg/ml concentration. The inhibition zones were
measured in millimeters at the end of an incubation
period of 48 h at 28 C. Dimethylformamide showed
no inhibition zones. Mycostatine was used as a stan-
dard reference fungicide to evaluate the potency of
the tested compounds. The minimal inhibitory con-
centration (MIC) of the active compounds was mea-
sured using the serial dilution method [20].
The results are illustrated in Table 2. The antifun-
gal activity of the synthesized compounds showed
that the halogenated triazoles having sulfonamide
moieties 2f, 4, 6, 8, 9b, and10 were found to be the
most active compounds IZ (24–40 mm) against all
the fungi under investigation, (MIC values were 100
␮g/ml). These results indicate that the biologically
active compounds 2f, 4, 6, 8, 9b, and 10 are nearly
as active as the standard Mycostatine (30 ␮g/ml).
4
8, 9b, and 10 in 10 M DMF Solution Before and After
Irradiation
-
Compound
Dose (kGy)
(1)
Abs./O.D.a
max
4
0b
5
275
0.460
0.471
0.481
0.574
0.579
0.630
0.657
0.657
1.272
1.421
1.433
1.544
1.624
2.044
2.173
2.249
1.373
1.566
1.633
1.648
1.652
1.673
1.748
1.811
0.926
1.208
1.335
1.342
1.349
1.349
1.629
1.640
10
15
20
25
30
40
0b
5
10
15
20
25
30
40
0b
5
10
15
20
25
30
40
0b
5
10
15
20
25
30
40
8
9b
10
285
290
280
RADIOSTABILITY OF THE BIOLOGICALLY
ACTIVE COMPOUNDS
The aim of the present work is to investigate the sta-
bility of the chemical structure of the biologically
aAbs./O.D. = absorbance/optical density.
bNonirradiated compound (control).

Amino Acids in the Syntheses of Heterocyclic Systems 323
[3] Kidwai, M.; Kumar, P. J Chem Res Synop 1996, 254–
255.
[4] Shafiee, A.; Naimi, E.; Mansobi, P.; Foroumadi, A.;
Shekari, M. J Heterocycl Chem 1995, 32, 1235–1239.
[5] Joshi, K. C.; Dandia, A.; Baweia, S. J Indian Chem
Soc 1989, 66, 690–693.
[6] Giri, S.; Singh, H.; Yadav, L. D. S.; Khare, R. K. J
Indian Chem Soc 1978, 55, 168–171.
[7] Holla, B. S.; Kalluraya, B. Indian J Chem, Sect B 1988,
27, 683–685.
[8] Farag, A. M. J Chem Res Synop 1995, 96–97.
[9] Abdel-Ghaffar, S. A.; Abbas, Y. A. Acta Pharm 1993,
43, 27–34.
[10] Jacobs, G. P. J Biomed Appl 1995, 10, 59–96.
[11] Boess, C.; Bogl, K. W. Drug Dev Ind Pharm 1996, 22,
495–529.
[12] Miyazaki, T.; Kaneko, T.; Yosshimura, T.; Crugq, A. S.;
Tilquin, B. J Pharm Sci 1994, 83, 68–71.
[13] Ghorab, M. M.; Shihab, A.; Heiba, H. I. Egypt J Radiat
Sci Appl 1995, 8, 191–198.
[14] Ghorab, M. M.; Mohamed, Y. A.; Mohamed, S. A.;
Ammar, Y. A. Phosphorus Sulfur Silicon 1996, 108,
249–256.
of nonirradiated (control) and irradiated compounds
in DMF as solvent are listed in Table 3.
The results showed that all the biologically ac-
tive compounds 4, 8, 9b, and 10 were radioresis-
tant, retaining their structure unchanged up to 40
kGy (the absorbance value above control). Also, thin
layer chromatographic analyses for compounds 4, 8,
9b, and 10 was conducted before and after irradia-
tion using precoated silica gel G sheet 1B-F and a
mixture of 2:1 ethylacetate–petroleum ether as elu-
ent. Spots were detected by use of a UV lamp at 254
nm. Compounds 4, 8, 9b, and 10 showed a single
distinct spot, before and after irradiation, with the
same R values of 0.42, 0.81, 0.94, and 0.90, respec-
f
tively. This means that no change occurred in the
structures of these compounds, so the radiosteriliza-
tion of these compounds in the dry form may prove
to be applicable.
[15] Ghorab, M. M. Egypt J Radiat Sci Appl 1995, 8, 179–
190.
ACKNOWLEDGMENT
[16] Basly, J. P.; Basly, I.; Bernard, M. Int J Radiat Biol
1998, 74(4), 521–528.
[17] Basly, J. P.; Basly, I.; Bernard, M. Int J Radiat Biol
1999, 75, 259–263.
We thank Dr M. M. Afifi, Microbiology Department,
Faculty of Science, Al-Azhar University at Assuit,
Egypt for doing the antifungal activity.
[18] McChesney, E. W.; Kirkswann, W. M. J Am Chem Soc
1937, 59, 1116–1118.
[19] Reeves, D. S.; White, L. O. Principles of methods of
assaying antibiotic in pharmaceutical microbiology,
3rd ed., Blackwell Scientific Publications: Oxford,
1983, pp. 140–162.
[20] Courvalin, P. Am Soc Microbiol News 1992, 58, 368–
375.
REFERENCES
[1] Likhate, M. A.; Fernandes, P. S. J Indian Chem Soc
1990, 67, 862–863.
[2] Ghorab, M. M.; Abdel-Hamide, S. G.; Ali, G. M.;
Shaurub, E. H. Pestic Sci 1996, 48, 31–35.