Synthesis of some more fluorine heterocyclic nitrogen systems derived from sulfa drugs as photochemical probe agents for inhibition of vitiligo disease-part i

Article abstract of DOI:10.1155/2011/586063

Some more new bioactive fluorine heterocyclic systems containing sulfur and nitrogen as five-membered rings: pyrazoline, imidazole, imidazolopyrimidine, thiazolidinone and 1,2,4-triazole derivatives (3-13) have been synthetically derived from the interaction of sulfa drugs with fluorine aromatic aldehyde and/or hexa fluoroacetic anhydride followed by heterocyclization reactions. Former structures of the targets have been deduced upon the help of elemental and spectral data.. Compounds 7a-f, 10c and 13 could be used as photochemical probe agents for inhibition of Vitiligo diseases, in compare with Nystatin and Nalidixic acid.

Full text of DOI:10.1155/2011/586063

ISSN: 0973-4945; CODEN ECJHAO
E-Journal of Chemistry
2011, 8(1), 405-414
http://www.e-journals.net
Synthesis of Some More Fluorine
Heterocyclic Nitrogen Systems Derived From
Sulfa Drugs as Photochemical Probe Agents for
Inhibition of Vitiligo Disease-Part I
REDA M. ABDEL-RAHMAN,
MOHAMMAD SALEH I.T. MAKKI and WAFA A.BAWAZIR
Department of Chemistry, Faculty of Science
King Abdul-Aziz University, P.O. Box 80203, Jeddah 21315, Saudi Arabia
wa_baker@hotmail.com
Received 11 February 2010; Accepted 7 April 2010
Abstract: Some more new bioactive fluorine heterocyclic systems containing sulfur
and nitrogen as five-membered rings: pyrazoline, imidazole, imidazolopyrimidine,
thiazolidinone and 1,2,4-triazole derivatives (3-13) have been synthetically derived
from the interaction of sulfa drugs with fluorine aromatic aldehyde and/or hexa
fluoroacetic anhydride followed by heterocyclization reactions. Former structures of
the targets have been deduced upon the help of elemental and spectral data..
Compounds 7a-f, 10c and 13 could be used as photochemical probe agents for
inhibition of Vitiligo diseases, in compare with Nystatin and Nalidixic acid.
Keywords: Synthetic, Fluoroheterocyclic, Inhibition of Vitiligo.
Introduction
In recent years, human pathogenic microorganisms have developed resistance in response to
indiscriminate use of commercial antimicrobial drugs commonly employed in the treatment
of infectious diseases1. On the other hand, fluorine organic and sulfa-compounds exhibited a
wide-range of pharmaceutical properties, in addition, a large number of heterocyclic nitrogen
systems showed biological activities as anti HIV and anticancer agents2-6. Thus, the present
work mainly aims synthesis of various fluorinated heterocyclic systems via combination of
both fluorine compounds and sulfa drugs in view of their use as photochemical probe agents
for inhibition of Vitiligo disease in compare with nystatin and nalydixic acid.
Experimental
Melting points were determined with an electrochemical Bibby Stuart Scientific melting
point SMP (US) apparatus. IR spectra recorded for KBr disc on a Perkin Lemer Spectrum RXI
FT-IR system No. 55529. H1 NMR were determined for solution in deuterated DMSO with a

406
WAFA A.BAWAZIR et al.
Bruker NMR advance DPX400 MH using TMS as an internal standard. 13C spectra were
recorded on a VXR-300 (75MHz) Varian spectrometer operating at room temperature. Mass
spectra were measured on GCMS-Q 1000-Ex Spectrometer. Electronic absorption spectra
were recorded on Shimadzu UV and Visible 3101 pc spectrophotometer. Microanalysis
(Sulfury) were performed by the Micro-analysis center of Cairo university, Egypt.
Methodology
Preparation of acetyl/benzoyl acetanilide (1a,b )
To preheated ethyl acetoacetate and /or benzoyl ethylacetoacetate (0.01 mol), sulfanilamide
(0.01 mol) was added then warmed at 100-110 °C for 15-20 min. The solid thus obtained was
washed with diethylether and dried to give 1a and 1b respectively. 1b C15H14N2SO4 (318
MW), S%: 9.30 (Calcd. 10.6), yield 75%: m.p 229-230 °C. IR-DRIFT: (cm-1), 3200, 3100,
3040, 2850, 1675, 1650, 1640, 1440, 1350; H1 NMR: δ 4.2(d, 2H), 5.20(s,1H), 6,8-6.5 (m,
5H), 7.7-7.5 (m,4H), 7.9 (s,1H), 1a, C10H12N2SO4 (256 MW); yield 70%: m.p. 177-178 °C;
S%: 11.87(Calcd. 12.5).
Synthesis of 3-arylamino-5-methyl/ phenyl-pyrazoline (2a, b)
Equimolar mixture of compound 1a,b and hydrazine hydrate in THF (50 mL) was refluxed
for 2 h then cooled. The resulted solid was crystallized from THF to give 2a and 2b
respectively. 2a: 10H12N4SO2 (252 MW), S%:11.92(Calcd. 12.69); yield 75%; m.p. 145-155 °C;
2b: C15H14N4SO2 (314 MW), S%: 9.17(Calcd. 10.1); yield 75%; m.p. 245-247 °C; IR-
DRIFT: (cm-1) 3200, 3129,1624, 1591, 1429, 1140, 768; H1 NMR: δ 7.9(s, 1H), 7.0-6.6
(m, 9H), 7.4 (s,1H), 5.4(s,1H), 3.4(s,1H), UV Vis (EtOH): λmax 276 nm.
Synthesis of 1-trifluoroacetyl-3-( sulfonamoyl phenyl-4-yl- trifluoro acetyl amino)-
5-phenyl pyrazoline (3)
To a mixture of compound 2b (0.01 mol) in THF (20 mL) and hexafluoro acetic anhydride
(0.02 mol) was added and refluxed for 2 h, cooled. The obtained solid was crystallized from
THF to give 3. C19H12N4F6SO4 (506 MW), S%: 6.0 (Calcd. 6.32); yield 80%, m.p.136-137 °C;
IR-DRIFT: (cm-1) 3020, 1760, 1683, 1503,1350, 850, 663; EI-MS: m/z (Int. %) 506 (3),
353(18), 255(19), 194(8), 185(10), 159(100), 143(18); UV Vis (EtOH): λmax 288 nm.
Preparation of oxazole-5-one derivative 4
A mixture of p-fluorobenzaldehyde (0.01 mol), hippuric acid (0.01 mol) in acetic anhydride
(50 mL), anhydrous sodium acetate (10 g) was refluxed for 4 h, cooled then poured onto ice.
The produced solid was washed with cold water and crystallized from glacial acetic acid to
give 4. C16H10NF6O2 (267, MW), yield 60%; m.p. 185-187 °C; IR-DRIFT: (cm-1) 3050,
2920, 1680, 1620, 1050,920,870, 650.
Synthesis of 1-(sulfonamoylphenyl)-4-(4`-fluorobenzylidene)imidazol-5-one (5)
Equimolar amounts of compound 4 and sulfapyridine in dry pyridine (100 mL) was heated
under reflux for 12 h, cooled then poured onto ice-HCl. The solid that obtained was filtered
off and washed with cold water and crystallized from dry pyridine to give 5. C27H19N4FSO3
(498 MW), S%: 5.97(Calcd. 6.42); yield 75%; m.p.169-170 °C; IR-DRIFT: (cm-1) 3240,
3059, 1790, 1596, 1390,1159, 1323, 870, 693; EI-MS: m/z (Int. %) 498(1), 341(5), 275(3),
266(18), 184(94), 107(8), 106(9), 104(100), 103(8); UV Vis (EtOH): λmax 385, 365, 348, 268 nm.
Synthesis of imidazolopyrimidinone (6)
A mixture of compound 5 (0.01 mol) and thiourea (0.01 mol) in ethanolic NaOH
(5%, 100 mL) was refluxed for 2 h, cooled then poured onto ice-HCl. The produced solid

Synthesis of Some More Fluorine Heterocyclic Nitrogen Systems
407
was filtered off and crystallized from EtOH to give 6. C28H21N6FSO3 (540 MW), S%: 5.56
(Calcd. 5.92); yield 75%; m.p.120 °C; IR-DRIFT: (cm-1) 3318, 3132, 1733, 1577,
1538,1444, 1374, 1351, 1218, 796, 692; H1 NMR: δ 10(s, 1H), 9.2 (s, 1H), 8.3-6.8 (m,13H),
4.3-4 (m,2H); UV Vis (EtOH): λmax 305, 275 nm.
Preparation of Schiff’s base 7(a-f)
Equimolar mixture of p-fluorobenzaldehyde and sulfa drugs; sulfanilamide, sulfabenz-
amide, sulfaisoxazole, sulfadiazine, sulfamerazine and sulfaguanidine respectively, in glacial
acetic acid (20 mL) was heated under refluxing for 1 h, cooled then poured onto ice. The
yielded solid was filtered off and crystallized from acetic acid to give 7a-f, in good yield 70%.
7a:C13H11N2FSO2 (278 MW), S%: 10.70 (Calcd. 11.51); m.p.129-130 °C.
7b:C20H15N2FSO3 (382 MW), S%: 7.95 (Calcd. 8.37); m.p.229-230 °C.
7c:C16H12N3FSO3 (345 MW), S%: 8.71 (Calcd. 9.27); m.p.211-212 °C.
7d: C17H13N4FSO2 (356 MW), S%: 8.08 (Calcd. 8.98); m.p.149-150 °C.
7e: C18H15N4FSO2 (370 MW), S%: 7.94 (Calcd. 8.64); m.p.359-360 °C.
7f: C21H16N4F2SO2 (426 MW), S%: 6.76 (Calcd. 7.51); m.p.186-187 °C.
7e; IR-DRI-FT: (cm-1) 3375, 1622, 1612, 1582, 1442, 1402, 1315, 1230, 789, 6714; UV Vis
(EtOH): λmax 375, 305, 275 nm.
Synthesis of 4-thiazolinones 8(a,b)
A mixture of 7e and/or 7f (0.01 mol) and thioacetic acid (0.02 mol) in dry dioxan (50 mL)
was refluxed for 12 h, cooled, then poured onto H2O-K2CO3. The obtained solid was
crystallized from dry dioxan to give 8a and/or 8b in 60% yield. 8a: C20H17N4FS2O3
(444 MW), S%: 13.54 (Calcd. 14.41); m.p.151-152 °C. EI-MS: m/z (Int. %) 444(4), 398(18),
370(12), 149(70), 123(82), 110(75), 109(100), 102(18). 8b: C23H18N4F2S2O3 (500 MW),
S%: 12.03 (Calcd. 12.80); m.p.156-157 °C; IR-DRI-FT: (cm-1) 3250, 1682, 1592, 1575,
1549, 1506, 1405, 1155, 792, 644 ; H1 NMR: δ 8.2(s, 1H),7.9-7.3, 7.2-6.7 (each m,4H, 4H),
4.3-4.0 (m,2H), 3.2(s,1H) 2.5(m, 2H); UV Vis (EtOH): λmax 400,328, 277 nm.
Synthesis of 5-trifluoroacetyl-2H-5H-2,3-diarylthiazolidin-4-one (9)
A mixture of compound 8b (0.01 mol) and hexafluoroacetic anhydride (1 mol) in THF
(20 mL) was refluxed for 2 h, cooled then poured onto ice. The produced solid was
crystallized from THF to give 9 in good yield 80%.C25H17N4F5S2O4 (596 MW), S%: 10.09
(Calcd. 10.73); m.p.130-132 °C; IR-DRI-FT: (cm-1) 3500, 3200, 3150, 3020, 2980, 1690,
1667, 1580, 1330, 820,664; UV Vis (EtOH): λmax 390, 279 nm.
Preparation of 1,2-diiminoaryl-3,4-dihydroxybutene (10a-c)
Equimolar amounts of squaric acid (0.01 mol) and the selective sulfa drugs as: sulfanilamide,
sulfabenzamide and or sulfamerazine (0.01 mol) in DMF (20 mL) was refluxed for 1 h,
cooled then poured onto ice and extracted with diethyl ether. The solid thus obtained was
crystallized to give 10a-c in good yield 80%.
10a:C16H14N4S2O6 (422 MW), S%: 14.09 (Calcd. 15.16); m.p.>360 °C.
10b:C30H22N4S2O8 (630 MW), S%: 9.54 (Calcd. 10.15); m.p.>360 °C.
10c:C26H22N8S2O6 (606 MW), S%: 10.03 (Calcd. 10.56); m.p.>360 °C.
Synthesis of 1,2-diiminoaryl-3,4-di(trifluoroacetoxy)-cyclo butene (11)
A mixture of compound 10b (0.01 mol) and hexafluoroacetic anhydride (1 mL) in THF
(20 mL) was warmed and refluxed for 1 h then cooled. The obtained solid was crystallized
from THF to give 11, in 75% yield. C34H20N4F6S2O10 (822 MW), S%: 7.31 (Calcd. 7.78);

408
WAFA A.BAWAZIR et al.
m.p. >360 °C; EI-MS: m/z (Int. %) 822 (8), 260(24), 239(28), 210(2), 194(34), 184(32),
156(28), 111(86), 109(100), 105(65); IR-DRI-FT: (cm-1) 3365, 1738, 1687, 1625,
1591,1537, 1305, 1091, 754, 681; H1 NMR: δ 8.0-7.9(s,1H,1H),7.8-7.6(m,18H), 4.3,4.1
(s,1H,1H); UV Vis (EtOH): λmax 410,350, 277 nm.
Preparation of N-di(trifluoroactyl)sulfanilamide (12)
A mixture of sulfanilamide (0.01 mol) in THF (50 mL) and hexafluoroacetic anhydride
(2 mL) was added drop wise then refluxed for 2 h, cooled. The obtained solid was
crystallized from THF to give 12, in good yield 70%; C10H6N2F6SO4 (364 MW), S%:
8.17(Calcd. 8.79); m.p. 212-213 °C; IR-DRI-FT: (cm-1) 3366, 1706, 1597, 1330, 1285, 1245,
769, 683; UV Vis (EtOH): λmax 350, 275 nm.
Synthesis of 3,5-di(trifluoromethyl)-4-(4`-sulfonamoylphenyl)-1,2,4-triazole (13)
To compound 12 (0.01 mol) in THF (20 mL), hydrazine hydrate (0.01 mol) was added drop
wise then refluxed for 2 h, cooled. The obtained solid was crystallized from THF to give 13 in
a good yield 70%; C10H6N4F6SO2 (360 MW), S%: 7.99(Calcd. 8.88); m.p. 195-2196 °C; IR-
DRI-FT: (cm-1) 3365, 1597, 1335, 1280, 1245,780, 680; H1 NMR: δ 8.1(s,2H),7.1-6.8(m,4H);
UV Vis (EtOH): λmax 276 nm. 13C NMR: δ 16.11(C3 of triazole), 116.7 (C of CF3), 132.2(N-
C1 of aryl), 129.9, 127.3 (C2 and C3 of aryl), and 143.7 ppm (O2S-C4 of aryl).
Results and Discussion
It has been observed that introduction of fluorine atoms or CF3 group to heterocyclic
systems acts as pharmacophore enhancing pharmacological properties of the compounds7.
For example incorporation of fluorine atoms into indole ring tends to increase drug
persistence by increasing its solubility in lipoid material and fat deposits in the body.
Thus, heterocyclization of acyl/benzoyl acetanilide 1a,b via refluxing with hydrazine
hydrate8,9 in THF led to the direct formation of 3-sulfanilamido-5-methyl/phenyl-1H-pyrazolines
(2a,b). Fluorination of 2 by warming the mixture with hexafluoro acetic anhydride in THF
produced 1-trifluoroacetyl-3-(trifluoroacetylaminoaryl-4-yl)-5-phenylpyrazoline 3 (Scheme 1).
A series of novel chiral imidazolines were prepared10 and used to develop the reactions
of various aromatic aldehyde with un activated acrylates and or alkyl vinyl ketones were
enantiomeric excesses obtained as metal-catalyzed reactions. Thus, 4-fluorobenzylidine-
oxazolin-5-one (4) used for the synthesis of polyfunctional imidazolone derivative 5 via a
simple nucleophilic attack by sulfapyridine in boiling dry pyridine. Cyclo addition of
compound 5 via refluxing with thiourea in ethanolic NaOH produced 6,7-dihydro-7-
(p-fluorophenyl)-2-phenyl-3-aryl-imidazolo[5,4-d]pyrimidine-5-one(6) (Scheme 2).
The use of heterocycles as chemical fertilizers to increase the yield of crops and as
pesticides to eliminate all kinds of parasites able to attack the cultivations is more becoming
important among these heterocycles thiazolidin-4-ones11-13. Thus, cycloaddition reactions of
thioglycollic acid with a type of Schiff’s bases 7 in boiling dry dioxan afforded 2,3-diaryl-
thiazolidin-4-ones (8a,8b). Full fluorinated compound 9 was obtained from boiling 8a with
hexafluoroacetic anhydride in dry THF (Scheme 3).
Sulfonamide azomethine derivatives containing H-C≡N group have wide medical
applications14. Recently, sulfanilamidohydrazone bearing azomethine moiety showed important
biological properties15. Thus, condensation of sulfa drugs such as sulfanilamide, sulfa benzamide
and sulfa merazine with squaric acid (2:1 by moles) in boiling acetic acid furnished the bis-imino
derivatives 10a-c, which upon boling with hexafluoroacetic anhydride in THF yielded 1,2-
(trifluoro -acetoxy)-3,4-di(p-sulfonamoyl phenyl)iminocyclo but-2-ene (11) (Scheme 4).

Synthesis of Some More Fluorine Heterocyclic Nitrogen Systems
409
O
C
O
C
O
C
H
2C
O H
+
H2N
SO2NH2
R
C
H2
OEt
+
F
C H O
H N
O
C
perheated
∆ 110ο
15 min
C
p h
4h
R: a: Me
b: ph
A c O /A cO H /
2
S od.su lphate anhyd rous
O
O
H
O
C
C
F
C
R
C
H2
N
H
SO2NH2
C
O
N
1(a,b)
4
THF
∆ 2h
N2H4
O
S N
D ry P yridin ne
∆
HN
C
N
C
H
2N
N
12 h
H
O
R
C
H
N
SO2NH2
F
H
2(a,b)
O
C H
N
O
O
THF
∆ 2h
N
S
N
H
F3C
F3C
C
C
N
O
O
5
O
F3COC
ph
S
C
N aO H (1 0% ) /E tO H
N
C
N
C
H 2
N
N H 2
∆ 4 h
C
H
N
COCF3
SO2NH2
O
F
H N
3b
N
Scheme 1
O
H
N
N
S
N
H
N
O
S
O
6
+
F
CHO
H N
2
N R
H
R= a: H
b:COph
O
∆ 1h
Gl.AcOH
N
c:
O
Scheme 2
O
S
N
N
d:
F
C
H
N
N
H
R
N
O
7(a-f)
e:
N
Me
7(e,f)
SHCH COOH
f:
Dry Dioxane
NH
N C
2
F
C
∆ 8h
H
O
N
N
F
NH
N
S
S
O
CH3
O
8(e, f)
O
8f
F C
3
C
C
THF
O
∆ 1h
F C
3
O
O
NH
F
N
NH C
C
F
N
S
H
S
O
O
9
F C
3
O
Scheme 3

410
WAFA A.BAWAZIR et al.
O
HO
HO
O
H
O
+
H
O
H2N
2 mole
S N R
H
O
O
O
N
S
O
C
C
C F 3
C F 3
+
Squaric acid
1mole
:
R= a: H
b: COph
c:
O
Gl.AcOH
∆
1 h
N H 2
N
∆ 30 min.
T H F
N
Me
O2
S
O
O
C
C
N
N R
H
F 3
C
C F 3
HO
N
N
HO
H
R
N
10(a-c)
S
O2
1 2
S O 2 N H 2
O
10b
F3C C
∆
2 h
ΤΗF/∆ 30 min.
H 2
N
N H 2 .H 2 O
O
T H F
F3C C
-H 2
O
O
O2
S
O
N
N
O
C
N
H
F 3
C
N
C F 3
F3C C O
F3C C O
N
N
H
N
O
S
O2
C
O
11 b
1 3
S O 2 N H 2
Scheme 4
Scheme 5
Bi-nucleophilic attack on the 1,3-bicarbonyl compounds under mild conditions is an
important process in synthetic organic chemistry, especially primary bi-nitrogen agents led
to the formation of functionalized 1,2,4-triazoles as good ligand and antifungal agents16,17
.
Thus, 3,5-di(trifluoromethyl)-4-aryl-1,2,4-triazole 13 was isolated from treatment of
sulfanilamide with excess hexafluoroacetic anhydride-THF to give N-di(trifluoroacetyl)-
sulfanilamide 12 followed by refluxing with hydrazine hydrate in boiling THF (Scheme 5).
Photochemical probe activity
Photodynamic therapy (PDT) is a cancer treatment leading to the selective destruction of
malignancies by visible light in the presence of a photosensetizer and oxygen3,4. Upon the
irradiation of visible light with appropriate wave length, the photosensetizer can drive
molecular oxygen into excited triplet state transferring energy into ground state molecular
oxygen to produce singlet molecular oxygen18. Activated singlet oxygen or reactive oxygen
species (ROS) in general, plays an important role in cytotoxic effects on tumor tissues. PDT
can be applied as an effective cancer treatment due to enhanced permeability and retention
(EPR) effect in tumors in comparison with normal tissues and is easily controlled by limiting
the area of light irradiation19. Thus, in present work we hope to synthesis of heterocyclic
systems bearing both fluorine and sulfa moieties for treatment of Vitiligo instade of 8MP-
PUVA drug20.
O
O
O
OCH3
8 MP-PUVA

Synthesis of Some More Fluorine Heterocyclic Nitrogen Systems
411
Biocidal effects
The synthesized compounds were tested in vitro against gram negative bacteria E. coli;
P. aeuroginosa and K. pneumonia and gram positive bacteria B. subtillics, S. auereus and
fungi A. fumigates; C. albicans using the agar diffusion disc method21 by placing pre-sterilized
filter paper disks (6 mm in diameter) impregnated with 50 µg/disk. DMF, which showed no
inhibition zones, was used as a solvent. Inhibition zones (IZ) of the tested compounds (mm)
were measured after 24-28 h incubation period 37 °C for bacteria and after 5 days incubation
period at 28 °C for fungi (Table 1). The minimal inhibitory concentration (MIC) (Tables 2& 3)
method of the biologically active compounds was applied using different concentrations per
disk against bacteria and fungi using nalidixic acid and nystatin as reference drugs.
Table 1. The preliminary screening of antimicrobial activity of the synthesized compounds
Microorganisms / Inhibition Zone mmc
Compd.
Gram +ve Bacteria
Gram +ve Bacteria
Fungi
No.
B.S.
1
S.A.
12
15
15
16
16
11
16
14
16
16
20
30
6
E.C.
P.A.
15
14
16
16
18
12
12
14
16
18
16
12
6
K.P.
C.A.
8
10
11
8
A.F.
8
6
10
12
14
14
14
10
10
12
14
10
14
30
6
16
16
16
16
16
16
16
16
16
16
16
22
10
5
7a
13
14
16
14
11
12
13
16
11
16
32
6
8
6
7b
7e
10
12
8
8
7f
8e
6
6
10a
10b
10c
11b
13
8
6
9
8
6
6
8
6
Na.*
Ny.*
6
10
6
32
*Na: Nalidixic acid, 30 µg/disk, Bioanalize, Egypt.*Ny: Nystatin, manufactured by Pasteur Lab., Egypt, NS
100 units.Microorganisms: Gram +ve. : B.S.: Bacillus subtilis S.A.: Staphylacoccus aureus Gram -ve. : E.C.
:Escherichia coli, P.A. : Pseudomonas aeuruginosa K.P. : Klebsiella Pneumonia Fungi : C.A. : Candida
albicans (Aucc-1720) A.F. :Aspergillus fumigates (AuMc-1924). (The sensitivity of microorganisms of the
compounds is defined in the following manners: Highly active: inhibition zone ≥ 12 mm, Moderately active:
inhibition zone 9-12 mm, Slightly active: inhibition zone 6-9 mm, Not sensitive: inhibition zone 6 mm.)
Table 2. MIC of the biological active compounds towards the Gram -positive bacteria*:
Inhibition zones, mm
Compd.
No.
5
B. subtilis
S. aureus
50
12
13
14
16
14
11
12
13
16
11
16
40
10
10
12
16
8
30
6
8
20
6
6
6
6
6
6
6
6
8
6
9
10
6
6
6
6
6
6
6
6
6
6
6
50
12
15
15
16
16
11
16
14
16
16
20
40
10
12
13
14
14
11
13
10
12
11
15
30
6
20
6
8
8
8
8
6
6
6
6
6
6
10
6
6
6
6
6
6
6
6
6
6
6
10
10
12
12
6
7a
7b
7e
9
10
6
7f
8e
9
6
1
10
8
8
10a
10b
10c
11b
13
10
16
11
16
9
12
6
9
9
12
8
* Concentration in µg / disk

412
WAFA A.BAWAZIR et al.
Table 3. MIC of the biological active compounds towards Gram –negative bacteria
Inhibition zones, mm
Compd.
No.
E. coli
P. aeuruginosa
K.Pneumonia
50 40 30 20 10 50 40 30 20 10 50 40 30 20 10
10
12
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
6
6
6
6
6
6
6
6
6
6
6
15 11 10
14 10 10
16 13 11
16 11 11
8
8
8
8
8
8
8
8
8
8
8
6
6
6
6
6
6
6
6
6
6
6
16 12 10
16 16 12
16 16 11
8
8
8
8
8
8
8
8
8
8
8
6
6
6
6
6
6
6
6
6
6
6
5
7a
14 12 10
14 11
14 13 12
7b
9
16 12
16 14 12
16 11
9
7e
18 11
9
8
8
8
8
7f
10
10
12
14
10
8
8
8
8
8
8
8
8
8
8
12
12
9
9
9
8a
16 13 11
16 12 10
10a
10b
10c
11b
13
14 10
16 14
16 11
9
18 14 12
16 12 10
16 11 10
16 11 10
14 12 10
Antimicrobial assays using UV (366 nm) light
This test was performed as mentioned before but the Petri-disks containing microorganisms
and the testing compounds were subjected to UV light (366 nm) for 3 h before transferred to
the incubation periods (Table 4).
Table 4. Preliminary screening using UV (366 nm) light
Microorganisms (Inhibition zones in mm)
Compd.
No.
Gram +ve bacteria
Gram -ve bacteria
Fungi
A.F.
B.S.
13
13
15
17
16
13
13
13
18
18
20
*
S.A.
E.C.
P.A.
17
16
16
18
20
14
15
18
22
20
20
*
K.P.
C.A.
9
12
10
5
7a
13
14
8
No
change
No
change
7b
7e
No
change
No
change
13
16
10
10
10
10
12
*
7f
8e
10a
10b
10c
11b
13
No
change
No
change
No
change
No
change
-
-
-
-
-
*Increasing in activity by using UV light (366 nm.)

Synthesis of Some More Fluorine Heterocyclic Nitrogen Systems
413
Conclusion
The present work reports a new investigation of fluorine bearing heterocyclic nitrogen
systems derived from sulfa drugs analogs as potential inhibitor for Vitiligo disease. All the
derivatives showed highly to moderate activities against tested microorganisms in compare
with standard antibiotic for Vitiligo as nystatin and nalidixic acid.
The obtained data suggest that fluorine Schiff’s base 7, imino squaric acid 10 and hexa
fluoro-1,2,4-triazole (13) should be considered a good scaffold for inhibitors of the
microorganisms which cause a Vitiligo disease.
From obtained results of the Biocidal effects of the tested compounds (Tables 1-4) we
conclude that:
•
In general, all the tested compounds were more highly active towards all tested
microorganisms, in compare with nystatin antibiotic.
•
MIC of all the active tested compounds showed activities more than nystatin,
especially toward B. subtilis, S.aureus and E.coli, P.aeuroginosa and K.
pneumonia
•
•
After using UV Visible light, the tested compounds showed an additional activity
especially towards B. subtilis, P.aeuroginosa and C.albicans.
The fluorinated heterocyclic nitrogen systems 7, 10 & 13 exhibited a highly
biocidal effects, which is mainly due to connection of fluorine groups at the
terminal of nitrogen/oxygen systems causing a type of biodynamic electron-motion
which led to use these systems as photochemical probe agents.
Acknowledgment
We greatly acknowledge Prof. Dr. Z.El-Bazza and her co-workers, Phrmamicrobiological
Lab., National Centre for Radiation Research and Technology, Cairo, Egypt, for financial
support to carrying out the antimicrobial assays, especially photo-synthetization activity
of cancer. I also indebted to the King Fahd Center at KAU for all laboratory facilities.
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