Synthesis, characterization and biological activity of Schiff base analogues of indole-3-carboxaldehyde

Article abstract of DOI:10.1016/j.ejmech.2007.03.022

Eight novel heterocyclic Schiff bases derived from the condensation reactions of indole 3-carboxaldehyde with different l-amino acids (histidine, glutamic acid, aspartic acid, leucine, valine) as well as with some aminophenols, have been synthesized and characterized by various spectroscopic methods (IR, MS, ¹H NMR). Schiff base derivatives of indole 3-carboxaldehyde were labeled with ^99mTc and radiochemical purity was above 97% which is ascertained by instant thin layer chromatography using different solvent conditions. Stability studies of all the derivatives of indole 3-carboxaldehyde was determined under physiological conditions and were stable for more than 24 h. Blood clearance showed a quick wash out from the circulation and biological half life was found to be t_1/2(F) = 1 h 15 min; t_1/2(S) = 10 h 05 min. Excellent quality radioimages of tumor bearing mice were recorded showing rapid clearance of background activity, visualization of tumor at 3 h and clearance from kidneys of histidine analogue which was further evidenced in biodistribution studies. Antimicrobial activity of these Schiff base compounds was evaluated against Bacillus subtilis, Pseudomonas fluorescence, Staphylococcus aureus, Aspergillus niger, Candida albicans and Trichophyton rubrum.

Full text of DOI:10.1016/j.ejmech.2007.03.022

Available online at www.sciencedirect.com
European Journal of Medicinal Chemistry 43 (2008) 160e165
http://www.elsevier.com/locate/ejmech
Short communication
Synthesis, characterization and biological activity of
Schiff base analogues of indole-3-carboxaldehyde
Deepa Sinha a,b, Anjani K. Tiwari a, Sweta Singh a, Gauri Shukla a,b,
Pushpa Mishra a, Harish Chandra b, Anil K. Mishra a,
*
a Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences,
Brig. S. K. Mazumdar Road, Delhi 110054, India
b Department of Chemistry, University of Delhi, Delhi 110007, India
Received 2 February 2007; received in revised form 14 March 2007; accepted 15 March 2007
Available online 7 April 2007
Abstract
Eight novel heterocyclic Schiff bases derived from the condensation reactions of indole 3-carboxaldehyde with different L-amino acids (his-
tidine, glutamic acid, aspartic acid, leucine, valine) as well as with some aminophenols, have been synthesized and characterized by various spec-
troscopic methods (IR, MS, 1H NMR). Schiff base derivatives of indole 3-carboxaldehyde were labeled with 99mTc and radiochemical purity was
above 97% which is ascertained by instant thin layer chromatography using different solvent conditions. Stability studies of all the derivatives of
indole 3-carboxaldehyde was determined under physiological conditions and were stable for more than 24 h. Blood clearance showed a quick
wash out from the circulation and biological half life was found to be t (F) ¼ 1 h 15 min; t (S) ¼ 10 h 05 min. Excellent quality radioimages
½
½
of tumor bearing mice were recorded showing rapid clearance of background activity, visualization of tumor at 3 h and clearance from kidneys
of histidine analogue which was further evidenced in biodistribution studies. Antimicrobial activity of these Schiff base compounds was evaluated
against Bacillus subtilis, Pseudomonas fluorescence, Staphylococcus aureus, Aspergillus niger, Candida albicans and Trichophyton rubrum.
Ó 2007 Elsevier Masson SAS. All rights reserved.
Keywords: Heterocyclic; Schiff base; Spectroscopic; Biodistribution; Antimicrobial
1. Introduction
Radiolabeled bio-molecules are potentially useful tools for
cancer diagnosis and therapy. Radiometals such as 99mTc(VII),
have physical properties, that are well suited for tumor imaging
with monoclonal antibodies, while 186Re(VII), 188Re(VII),
have cytotoxic properties which can be exploited for therapy
by antibody-directed tumor targeting. Many efforts have been
made to develop diagnostic pharmaceuticals of 99mTc-labelled
small molecular complexes because of the superior medico-
imaging characteristics (biological t1/2, low energy content)
and the availability of radionuclide [9]. Since the small size
of the complex is very important for the retention of the bioac-
tivity [10], one of the strategies in the investigation is to explore
novel complexes with small size, multifunctional ligands that
possess specific bioactivities. Amino acids, mono/disaccha-
rides and vitamins are some good examples for these applica-
tions. Some applications of these Schiff bases with favorable
Compounds with the structure of eC]Ne (azomethine
group) are known as Schiff bases, which are usually synthe-
sized from the condensation of primary amines and active car-
bonyl groups. Schiff bases are important class of compounds
in medicinal and pharmaceutical field. They show biological
applications including antibacterial [1e6], antifungal [3e6]
and antitumor activity [7,8]. Similarly indole derivatives are
prepared for a long time for a variety of biological activities
such as CNS depressant, anticancerous, antibiotic, antihista-
minic, anticonvulsants and many others.
* Corresponding author. Tel.: þ91 1123905117; fax: þ91 1123919509.
E-mail addresses: mis_ak@rediffmail.com, akmishra@gmail.com (A.K.
Mishra).
0223-5234/$ - see front matter Ó 2007 Elsevier Masson SAS. All rights reserved.
doi:10.1016/j.ejmech.2007.03.022

D. Sinha et al. / European Journal of Medicinal Chemistry 43 (2008) 160e165
161
cell membrane permeability have been exploited in cancer
multidrug resistance [9].
confirms the formation of the proposed Schiff base framework.
The infrared spectra of the complexes (Table 1) show a weak
intensity absorption band in the frequency range 1530e
1520 cmꢀ1 for the coordinated imine function n(CN).
Based on the mentioned properties of Schiff bases and in-
dole analogues we report herein their synthesis, spectroscopic
characterization as well as their efficacy for tumor imaging
after labeling with 99mTc. Antimicrobial activity of these
biologically important unsymmetrical Schiff bases of indole
3-carboxaldehyde with different amino acids (histidine,
glutamic acid, aspartic acid, valine, leucine) as well as some
aminophenol analogues (2-aminophenol, 2-aminophenol-
4-sulphonic acid, 1-amino-2-naphthol-4-sulfonic acid) are
also mentioned.
In this work, we have used optically active amino acids and
substituted aromatic amines to prepare Schiff base compounds
as reported in literature [11e14]. Presence of eC]Ne and
other functional groups forms more stable complexes com-
pared to Schiff bases having only eC]Ne coordinating moi-
ety. For nuclear medicine applications, novel derivatives, of
indole 3-carboxaldehyde with amino acids or substituted aro-
matic amines have been synthesized. Their synthesis, radiolab-
eling, radioimaging and antimicrobial activity are described
herein.
2.3. Antibacterial studies
The newly prepared compounds were screened for their an-
tibacterial activity against Bacillus subtilis, Staphylococcus au-
reus and Pseudomonas fluorescence by disc diffusion method
[15,16]. A standard inoculum (1e2 ꢁ 107 c.f.u./ml 0.5 McFar-
land standards) was introduced onto the surface of sterile agar
plates, and a sterile glass spreader was used for even distribu-
tion of the inoculum. The discs measuring 6.25 mm in diame-
ter were prepared from Whatman no. 1 filter paper and
sterilized by dry heat at 140 ꢂC for 1 h. The sterile discs pre-
viously soaked in a known concentration of the test com-
pounds were placed in nutrient agar medium. Solvent and
growth controls were maintained. The plates were inverted
and incubated for 24 h at 37 ꢂC. Ciprofloxacin was used as
a standard drug. The inhibition zone were measured and com-
pared with the controls. The bacterial zone of inhibition values
are given in Table 2. Minimum inhibitory concentration (MIC)
was determined by broth dilution technique. The nutrient
broth, which contained logarithmic serially two-fold diluted
amount of test compound and controls, was inoculated with
approximately 5 ꢁ 105 c.f.u. of actively dividing bacterial
cells. The cultures were incubated for 24 h at 37 ꢂC and the
growth was monitored visually and spectrophotometrically.
The investigation of antibacterial screening data revealed
that all the tested compounds showed moderate to good bacte-
rial inhibition.
2. Experimental
2.1. Materials and methods
All chemicals used in the present study are of analytical
grade purchased from Sigma, Aldrich and Merck chemical
co. All the solvents were used after distillation. TLC was run
on the silica coated aluminium sheets (silica gel 60 F254, E
Merck, Germany) and visualized in UV light. IR spectra
were recorded on the FT-IR Perkin Elmer spectrum BX spec-
trophotometer. NMR spectra were obtained by using Brucker
NMR instrument 300 MHz. The MS spectra were recorded
from JEOL SX 102/DA-6000 spectrometer using m-nitroben-
zyl alcohol as matrix. Elemental analysis was done on elemen-
tal analyzer system Gmbh variable system. Radiocomplexation
and radiochemical purity were checked by instant strip chro-
matography (silica gel impregnated paper chromatography)
with IILC-SG (Gelman Sciences, Ann arbor, MI, USA).
2.4. Antifungal studies
The newly prepared compounds were screened for their an-
tifungal activity against Aspergillus niger, Candida albicans
and Trichophyton rubrum in DMSO by serial plate dilution
method [17,18]. Sabourand agar media were prepared by dis-
solving peptone (1 g), D-glucose (4 g) and agar (2 g) in dis-
tilled water (100 ml) and adjusting pH to 5.7. Normal saline
was used to make a suspension of corresponding species.
Twenty milliliters of agar media was poured in each petri
dish. Excess suspension was decanted and the plates were
dried by placing in an incubator at 37 ꢂC for 1 h. Using an
agar punch wells were made into each well labelled. A control
was also prepared in triplicate and maintained at 37 ꢂC for
3e4 days. The fungal activity of each compound was com-
pared with that of flucanozole as standard drug. The inhibition
zones were measured and compared with controls. The fungal
zone of inhibition values are given in Table 2. The nutrient
broth, which contained logarithmic serially two-fold diluted
amount of test compound and controls, was inoculated with
approximately 1.6 ꢁ 104e6 ꢁ 104 c.f.u./ml. The cultures
were incubated for 48 h at 35 ꢂC and the growth was
monitored.
2.2. Preparation of Schiff base
The Schiff base used was prepared by mixing an ethanolic
solution (25 ml) of 1.45 g (0.01 mol) of indole 3-carboxalde-
hyde with 0.01 mol of other moiety in the same volume of eth-
anol. The mixture was then refluxed with stirring for 2e6 h.
The precipitate was collected by filtration through Buchner
funnel, recrystallized from ethanol, and dried at room temper-
ature with 60e85% yield.
The IR spectrum of the Schiff bases (Table 1) shows very
strong intensity absorption band at 1450e1590 cmꢀ1 assigned
to CN stretching mode. The presence of aromatic rings has
been identified by their characteristic ring vibrations at
1450e1400, 1100e1090 and 760e720 cmꢀ1 regions. The ab-
sence of bands characteristic of n(CO), primary amine n(NH)

162
D. Sinha et al. / European Journal of Medicinal Chemistry 43 (2008) 160e165
Table 1
Spectral analysis of Schiff bases
Name of the compound
Spectral data
3-(3H-Imidazol-4-yl)-2-[(1H-indol-3-ylmethylene)-amino]-propionic acid (1)
MP 112 ꢂC; UVevis: 280 nm; IR (KBr): 1423, 1576, 3258 cmꢀ1
;
1H NMR (300 MHz, CDCl3): d (ppm) 2.5 (t, 1H, CH), 2.6 (d, 2H, CH2),
6.8e7.6 (m, 7H, ArH), 7.3 (d, J ¼ 8.1 Hz, 1H), 7.5 (s, 2H, CH2);
13C NMR (DMSO-d6, ppm): 166 (C]N), 179.5, 69.2, 33.2; MS (EI):
m/z (282), M þ 2Naþ (328); elemental analysis: C15H14N4O2 C (62.62%),
H (5.1%), N (18.81%)
2-[(1H-Indol-3-ylmethylene)-amino]-pentanedioic acid (2)
MP 128 ꢂC; UVevis: 235 nm; IR (KBr): 1123, 1390, 2695 cmꢀ1
;
1H NMR (300 MHz, CDCl3): d (ppm) 1.8, 2.3 (t, 2H, CH2), 2.4 (t, 1H, CH),
7.2e7.7 (m, 5H, ArH), 7.2 (d, J ¼ 7.7 Hz, 1H), 7.6 (s, 1H, CH);
13C NMR (DMSO-d6, ppm): 162.3 (C]N), 68.4, 180.1, 28.2; MS (EI):
m/z (274), M þ 3Naþ (343); elemental analysis: C14H14N2O4 C (60.24%),
H (4.94%), N (9.71%)
2-[(1H-Indol-3-ylmethylene)-amino]-succinic acid (3)
MP 207 ꢂC; UVevis: 235 nm; IR (KBr): 1145, 1468, 3392 cmꢀ1
;
1H NMR (300 MHz, CDCl3): d (ppm) 2.5 (d, 2H, CH2), 2.7 (t, 1H, CH),
7.0e7.3 (d, J ¼ 8.1 Hz, 1H), 7.4 (s, 1H, CH); 13C NMR (DMSO-d6, ppm):
169.2 (C]N), 180.0, 65.1, 38.5; MS (EI): m/z (260), M þ Kþ (337);
elemental analysis: C13H12N2O4 C (60.12%), H (4.12%), N (10.54%)
2-[(1H-Indol-3-ylmethylene)-amino]-4-methyl-pentanoic acid (4)
2-[(1H-Indol-3-ylmethylene)-amino]-3-methyl-butyric acid (5)
MP 119 ꢂC; UVevis: 224 nm; IR (KBr): 915, 1156, 1480 cmꢀ1
;
1H NMR (300 MHz, CDCl3): d (ppm) 1.2 (d, 6H, CH3), 1.8 (m, 1H, CH),
7.1e7.7 (m, 5H, ArH), 7.3 (d, J ¼ 8.5 Hz, 1H), 7.6 (s, 1H, CH);
13C NMR (DMSO-d6, ppm): 161.7 (C]N), 67.8, 42.6; MS (EI): m/z (258);
elemental analysis: C15H18N2O2 C (68.71%), H (6.92%), N (9.82%)
MP 161 ꢂC; UVevis: 248 nm; IR (KBr): 1396, 1592, 3286 cmꢀ1
;
1H NMR (300 MHz, CDCl3): d (ppm) 1.5 (d, 6H, CH3), 2.1 (d, 1H, CH),
2.2 (m, 1H, CH), 7.0e7.8 (m, 5H, ArH), 7.7 (s, 1H, CH),
7.2 (d, J ¼ 7.7 Hz, 1H); 13C NMR (DMSO-d6, ppm): 166.9 (C]N),
77.3, 26.9; MS (EI): m/z (244); elemental analysis: C14H16N2O2 C (67.54%),
H (5.94%), N (10.97%)
2-[(1H-Indol-3-ylmethylene)-amino]-phenol (6)
MP 97 ꢂC; UVevis: 272, 348 nm; IR (KBr): 1245, 1495, 3421 cmꢀ1
1H NMR (300 MHz, CDCl3): d (ppm) 6.2e7.7 (m, 9H, ArH),
;
7 (d, J ¼ 8.6 Hz, 1H), 7.8 (s, 1H, CH); 13C NMR (DMSO-d6, ppm): 159.9
(C]N), 137.6, 72.3; MS (EI): m/z (236); elemental analysis: C15H12N2O C
(74.21%), H (5.02%), N (10.92%)
3-Hydroxy-4-[(1H-indol-3-ylmethylene)-amino]-naphthalene-1-sulfonic acid (7) MP 214 ꢂC; UVevis: 258, 384 nm; IR (KBr): 1156, 1468, 3356 cmꢀ1
1H NMR (300 MHz, CDCl3): d (ppm) 6.8e7.7 (m, 10H, ArH), 7.5
;
(s, 1H, CH), 7.6 (d, J ¼ 8.8 Hz, 1H); 13C NMR (DMSO-d6, ppm): 168.1
(C]N), 132.7, 91.3; MS (EI): m/z (366); elemental analysis: C19H14N2O4S C
(61.20%), H (3.75%), N (7.56%)
2-[(1H-indol-3-ylmethylene)-amino]-phenol-1-sulfonic acid (8)
MP 115 ꢂC; UVevis: 326 nm; IR (KBr): 1156, 1495, 3420 cmꢀ1
;
1H NMR (300 MHz, CDCl3): d (ppm) 6.2e7.97 (m, 8H, ArH), 7.7
(d, J ¼ 8.6 Hz, 1H), 7.8 (s, 1H, CH); 13C NMR (DMSO-d6, ppm): 159.6
(C]N), 137.6, 70.3; MS (EI): m/z (316); elemental analysis: C15H12N2SO4
C (56.21%), H (3.82%), N (8.92%)
Table 2
Microbial activity of Schiff bases
Minimum inhibitory
concentrations (mg/ml)
Compound
Bacillus subtilis
Pseudomonas fluorescence
Staphylococcus aureus
Aspergillus niger
Candida albicans
Trichophyton rubrum
1
2
3
4
5
6
7
8
35.1
48.2
11.3
12.1
42.5
18.4
15.5
13.5
3.8
5.7
3.4
19.2
18.5
35.3
16.8
35.9
>50
>50
47.5
>50
17.8
>50
>50
>50
21.3
25.6
>50
12.5
11.9
19.9
26.8
28.4
15.2
>50
>50
>50
16.2
>50
>50
>50
21.9
19.4
19.3
>50
38.1
15.8
21.6
11.3

D. Sinha et al. / European Journal of Medicinal Chemistry 43 (2008) 160e165
blood kinetics
163
2.5. Radiolabeling of the compounds with 99mTc
45
40
35
30
25
20
15
10
5
his
glut
Hundred microliters of 0.03 nM solution of the compounds
were dissolved in DMSO and taken in a shielded vial and
60 ml of 1 ꢁ 10ꢀ2 M SnCl2$2H2O (dissolved in N2 purged
1 ml 10% acetic acid) was added followed by addition of
(<1 h) freshly eluted saline solution of sodium pertechnetate
(NaTcO4) (74 MBq, 100 ml). The pH of the reaction mixture
was adjusted to 6.5 with 0.1 M NaHCO3 solution and shook
to mix the contents. The vial was allowed to stand for 20e
30 min at room temperature. Labeling of the compound, radio-
chemical purity as well as Rf of the 99mTc based complex was
determined by ITLC-SG strips using 0.9% NaCl aqueous solu-
tion (saline) as developing solvent and simultaneously in ace-
tone and PAW (pyridine, acetic acid and water in 3:5:1.5
ratio). Each ITLC was cut into 0.1 cm segments and counts
of each segment were taken.
0
0
5
10
15
time (hr)
20
25
30
Fig. 1. Blood kinetics study in rabbit.
The actual amount of radioactivity administered to each ani-
mal was calculated by subtracting the activity left in the tail
from the activity injected. Radioactivity accumulated in each
organ was expressed as percentage administered dose per
gram of tissue. Total volume of the blood was calculated as
7% of the body weight.
2.6. In vitro serum stability assay
The fresh human serum was prepared by allowing blood
collected from healthy volunteers to clot for 1 h at 37 ꢂC in
a humidified incubator maintained at 5% carbon dioxide,
95% air. Then the sample was centrifuged at 400 rpm and
the serum was filtered through 0.22 mm syringe filter into ster-
ile plastic culture tubes. The above freshly prepared techne-
tium radiocomplexes were incubated in fresh human serum
at physiological conditions, i.e. at 30 ꢂC at a concentration
of 100 nM/ml and then analyzed by ITLC-SG at different
time intervals to detect any dissociation of the complex. Per-
centage of free pertechnetate at a particular time point that
was estimated using saline and acetone as mobile phases, rep-
resented percentage dissociation of the complex at that partic-
ular time point in serum.
3. Results and discussion
Synthesis of Schiff bases have been achieved in high yields
starting from the condensation reaction of indole
3-carboxaldehyde and L-amino acids such as histidine, aspartic
acid, glutamic acid, valine, leucine (as all these are important
in the metabolism and mechanism proposed for tumor as
well as due to their strong affinity for donar sites in physiolog-
ical reaction conditions) as well as some aminophenol
analogues (2-aminophenol, 2 aminophenol-4-sulphonic acid,
1-amino-2-naphthol-4-sulphonic acid) as reported in literature
2.7. Blood kinetics studies
Table 3
Biodistribution study of histidine and glutamic acid analogues
The blood clearance study was performed in albino New
Zealand rabbits weighing approximately 2.5e3.0 kg after ad-
ministration of 10 MBq of the 99mTc labeled compounds in
0.3 ml via the ear vein. At different time intervals about
0.5 ml blood samples were withdrawn from the dorsal vein
of other ear and radioactivity was measured in the gamma
counter. The data from the experiment were expressed as per-
centage of administered dose at each time interval in Fig. 1.
Organs
Uptake (% ID/g)
After 1 h
After 2 h
After 4 h
After 6 h
After 8 h
Histidine
Stomach
Intestine
Brain
1
0.5
0
2.5
0.5
0.2
3
0.2
0.45
18
14
2
3
3
3.0
3
1
1
Liver
18
10
5
25
15
12
6
15
11
6
Spleen
Kidney
Blood
15
7
2.8. Biodistribution studies
3
2
0.4
2
0.3
0.5
0.3
0.5
0.2
Heart
1
Albino mice strain (A) was used for the tissue distribution
studies. Animal handling and experimentation was carried out
as per the guidelines of the Institutional Animal Ethics
Committee.
An equal dose of 10 mCi of labeled test compound was in-
jected in mice through tail vein of each animal. At different
time intervals mice were sacrificed, blood was collected and
different tissues and organs were dissected and analyzed in
Table 3. The radioactivity was measured in a gamma counter.
Glutamic acid
Stomach
Intestine
Brain
1
2.0
0.5
0.2
3
0.2
0.45
14
17
7
3
1
3.0
1
0.5
0
1
1
Liver
16
10
23
15
6.0
15
16
4.5
2.5
0.1
15
16
4.5
2.5
0.2
Spleen
Kidney
Blood
Heart
5.5
2.5
0.8
2
0.5
2
0.2

164
D. Sinha et al. / European Journal of Medicinal Chemistry 43 (2008) 160e165
[1e3,9e11]. The synthesized ligands were checked by compar-
ing the TLC with the starting materials, which resulted in a sin-
gle spot different from the starting materials. IR studies of each
compound confirms the formation of eC]Ne bonds as well as
lack of eC]Oe from original aldehydic compounds. 1H NMR
spectra, respectively, confirm the proposed stoichiometry and
structure for the Schiff bases. The signal of azomethine protons
de-shielded in the spectra of Schiff bases was found to occur at
lower ppm. Integral of NMR confirms the number of protons in
Schiff bases as well as coupling constant which confirms the
formation of eC]Ne bonds.
The Schiff bases were tested for antimicrobial activity
against B. subtilis, P. fluorescence, S. aureus, A. niger, C. albi-
cans and T. rubrum. The microbial activity shows that com-
pound 1 and compound 2 have very good activity against
P. fluorescence, S. aureus while compound 3 shows good activ-
ity against all the species which is due to additional polarity in
amino acid analogues. In the synthesized compounds, three
amino acids having additional acidic/basic moieties showed
good activity. Compound 7 which is a naphthalene derivative
having higher aromaticity than other compounds showed good
activity against B. subtilis, P. fluorescence, S. aureus.
complexation of novel synthesized compounds with 99mTc
was found to give sufficiently stable complexes under
physiological conditions. Complexes of indole 3-carboxalde-
hyde-histidine and indole 3-carboxaldehyde-aspartic acid
showed very good tumor uptake, while remaining analogues
showed poor uptake in tumor (indicating no potential of the
complexes in tumor imaging). Good bone uptake of indole
3-carboxaldehyde-aspartic acid, and indole 3-carboxaldehyde-
glutamic acid, high spleen accumulation of histidine, valine
and leucine and non-specific biodistribution of indole 3-
carboxaldehyde-aminophenol were observed. In vitro serum
stability of the radiocomplexes is a necessary parameter meant
to measure the effectiveness of chelating moiety to coordinate
the radiometal. Generally there is transchelation of radiometal
to serum proteins particularly albumin. In vitro serum stability
of the complexes clearly indicates that initially there was fall
in the stability of the complex but later on it shows a constant
stability. Initial fall in the labeling efficiency after addition of
fresh serum could be attributed to the transchelation that could
have taken place in serum due to high affinity of plasma pro-
teins for metal ions.
The retention of drug in the blood of the animal depends
upon the pharmacological and physical properties of the drugs.
Nearly all the Schiff bases show a very rapid fast clearance of
The radiolabeling study under physiological conditions was
done as reported in the literature [19e21]. Preliminary
Fig. 2. Imaging of Schiff bases (histidine analogue) in rabbit.

D. Sinha et al. / European Journal of Medicinal Chemistry 43 (2008) 160e165
165
4. Conclusion
The preliminary studies with these novel Schiff base
ligands are encouraging to carry out further in vivo experi-
ments for targeted imaging of human tumor. The therapeutic
potential of these complexes can further extend by applying
these in different animal models and cell lines.
Acknowledgement
We thank Dr. R.P. Tripathi, Director, INMAS, for providing
all the facilities and for his deep interest and constant encour-
agement during the course of the study.
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Biodistribution of the radiocomplexes is an important phe-
nomenon to study because it gives an idea how the radiocom-
plex drugs distribute in vivo and how it excretes. Accumulation
of low amount of radioactivity in the stomach precludes the
presence of free pertechnetate going to stomach which in-
dicates in vivo stability of preparation. The distribution in var-
ious organs of mice is shown as percentage of injected dose per
organ or tissue at different time intervals. It seems that drug is
localized in the liver and kidneys, with passage of time, the ac-
tivity of kidney was increased in most of the compounds, while
if it is in the intestine there was negligible increase in activity.
This shows that major route of excretion of activity is through
kidneys. This was supported by radioimages of tumor bearing
mice (Fig. 3) as with passage of time, there was increased ac-
cumulation of activity in urinary bladder. Besides that the ra-
dioactivity remained in liver for very longer time, indicating
that most probably the metabolism of drugs may be taking
place in liver, but the excretion of drugs and metabolites is
mainly through kidney. Accumulation of drugs in liver may
also be because of protein binding nature of drugs. Very little
accumulation in lungs, spleen and stomach was observed, neg-
ligible accumulation occurs in heart and brain. The best results
of blood kinetics and imaging is given in Figs. 1e3.
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