Increased uptake of glutamic acid is observed in
tumor cells due to increased metabolic activity. Hence
B27 Studies On Some Novel Thieno[2,3-d]-
Pyrimidine: Part I. Synthesis &
Antimicrobial Evaluation Of 4-Imino, 3-
(Substituted Benzothiazole-2-Yl), 5,6,
Disubstituted Thieno (2,3-d) Pyrimidine
2(1H)- Thiones.
Laddha SS1, Patil SG1, Surana SJ*1, Ganguly S2, &
Bhatnagar SP2
1 Medicinal Chemistry Division, R. C. Patel College of
Pharmacy, Shirpur, Dist: Dhule.
2 Dept. of Pharmaceutical Sciences, Birla Institute of
Technology, Mesra, Ranchi.
The clinical need for an antimicrobial has related
in series of papers appearing on the synthesis, prelimi-
nary screening of various nitrogen heterocyclic systems,
especially pyrido (2,3-d) pyrimidine and thieno (2,3-d)
pyrimidine.
Numerous thieno (2,3-d) pyrimidines are known to
possess a broad spectrum of biological activities. Some
of them are useful as antifolates, antihyperlipademic,
analgesics and antibacterial activity. Also many
benzothiazole derivatives have been found application
as analgesics, anti-inflammatory and antibacterial. In view
of these benefits and as a continuation of our work, the
present investigation was planned to synthesize novel 4-
imino, 3-(substituted benzothiazole-2-yl), 5,6, disubsti-
tuted thieno (2,3-d) pyrimidine 2(1H)-thiones in the hope
of obtaining compounds with both thieno (2,3-d) pyrimi-
dine and benzothiazole nucleus in a single framework
with enhanced biological and medicinal properties.
The starting compounds 3-cyano, 2-amino, 4,5-dis-
ubstituted thiophen (Gewalds) has been prepared by re-
ported method. Gewald was treated with CS2 in dry pyri-
dine using the known method gives 4-imino, 5,6, disub-
stituted thieno (2,3-d) 1,3 thiazine-2-thione. 4-imino, 5,6,
disubstituted-thieno (2,3-d) 1,3 thiazine-2-thione on re-
action with 2-amino benzothiazoles in the presence of
dry pyridine yielded various derivatives of 4-imino, 3-(sub-
stituted benzothiazole-2-yl), 5,6, disubstituted thieno (2,3-
d) pyrimidine 2(1H)-thiones. The structure of the final
compound was derived from Elemental analysis and
spectral studies (IR, NMR).
The title compounds were tested for their Antimi-
crobial activity and several of the title product shows prom-
ising antibacterial activity against both Gram positive and
Gram negative bacteria.
B28 Synthesis and Evaluation of L-Glutamic
Acid Analogs as Potential Anti-Cancer
Agents.
Lokhande T. N.*, Viswanathan C. L. and Deb S.
Bombay College of Pharmacy, Santacruz (E), Mumbai –98.
56th IPC Kolkata - Scientific Oral Presentations - Medicinal Chemistry
agents that can interfere with the uptake, biosynthesis or
functions of glutamic acid can act as antitumour agents.
For example, L-glutamic acid analogs have been re-
ported to have antitumour activity. Hydrazine moiety
showed potential for improving anticancer and
anticachexia activity. In the present work the synthesis of
four novel glutamic acid analogs with structure N-
(benzenesulphonyl)-L-glutamic acid bis-( substituted
phenylhydrazides) are reported. The substituents on the
phenyl hydrazide moiety are p-H, NO2, Cl & CH3.
i)Benzenesulphonyl chloride was condensed with
L-glutamic acid in basic medium to obtain N-
(benzenesulphonyl)-L-glutamic acid. Dry N-
(benzenesulphonyl)-L-glutamic acid was converted to N-
(benzenesulphonyl)-L-glutamic acid dichloride by reflux-
ing with thionyl chloride. ii) Synthesis of p-substituted
phenyl hydrazines involved diazotisation of p-substituted
anilines using NaNO2 & HCl followed by reduction using
sodium sulphite Alternatively the p-nitro isomer was pre-
pared by nucleophilic substitution of p-bromo nitroben-
zene with hydrazine hydrate. The acid chloride of step (i)
was refluxed with p-substituted phenylhydrazines of step
(ii) in anhydrous THF to get N-(benzenesulphonyl)-L-
glutamic acid bis-( substituted phenylhydrazides) having
substituents like p-H, CH3, Cl & NO2 .
Anticancer activity was determined for the com-
pounds in two prostate cancer cell lines (DU 145 & PC 3)
by using MTT assay. Adriamycin was used as the
standrard for the comparison. Out of four compounds,
the p-nitro isomer exhibited potent anticancer activity and
in cell line DU 145 its activity (84.7 %) is comparable to
adriamycin (86.6%) at 80 µg/ml. Also in PC-3, it showed
72.0 % inhibition as compared to adriamycin (98.3%) at
80 µg/ml.
B29 Synthesis Of P-Chlorophenyl
Semicarbazones As Potential
Anticonvulsants-And Their Effect On
Gaba Shunt
S.K.Patnaik, S.N.Pandeya, S.V.Chaudhari, N.Mahajan,
D.Thakkar*
Department of Pharmaceutics, Institute of Technology,
Banaras Hindu University, Varanasi - 221 005
Anticonvulsant drugs selectively depress the cen-
tral nervous system and are used in the treatment of Epi-
lepsy. The past few decades, experienced a great variety
of chemical compounds have been tried for the cure of
epileptic seizures.
Various compounds related to semicarbazone,
thiosemicarbazones and hydrazones were designed and
synthesized with the aim to develop newer anticonvulsants.
39
 O PMR and Mass) data. The synthesis has been effected
NH C
NH
Cl N
N NH C
Cl H 3C C S
HC
OH
I II
Cl N S
Cl
O
C
NH C
S
HC N
NH
HC
OCH 3
III
1
These compounds were characterized by UV, IR,
H NMR spectral and elemental analysis. All the synthe-
sized compounds were screened for their anticonvulsant
activity against maximal electroshock seizures test, strych-
nine induced seizure method, and Metrazole induced
seizure method in which all the compounds were found
to have anticonvulsant activity.
Further, the compounds were evaluated for their
effect on GABA levels in various regions of brain in rat by
enzymatic UV and fluorimetric method, using clobazam
as a standard drug. It was found that overall these com-
pounds increased the GABA levels in rat brain in the range
of 10% to 50% with maximum rise in cerebellum, while
the rise by clobazam was found to be 40%. The results
show that among all synthesized compounds; compound
I,(4-(4’-chlorophenyl)-4-hydroxyacetophenone
semicarbazone) was found to be more active than Clobazam.
Thus it can be predicted that the anticonvulsant prop-
erty of the synthesized compounds might be due to their
influence of GABA mediated inhibition and the chloro sub-
stituent at position para to the semicarbazone along with
NH-CO-NH-N= linkage is essential for their potential
anticonvulsant activity.
B31 Rapid one-Pot Microwave-assisted
Double Mannich Condensation of
Polysubstituted Cyclohexanones and
Pharmacological Activities of Their
Derivatives
Navanath Kalyane*, B. Shivakumar and V.M.Reddy**
1 Karnataka College of Pharmacy PO Box 53, Bidar.
2 Dr. Ch. Ravi Shankar Memorial Medicinal Chemistry
Research Laboratory, University College of Pharma-
ceutical Sciences, Kakatiya University, Warangal.
In view of growing pharmacological importance of
azabicyclononanes and their synthesis a more facile, rapid
one-pot and microwave irradiation method has been stud-
ied for their synthesis and compared with the conven-
tional one, in the present investigation. As many as thirty
new substituted 8-aryl-3-alkyl/aralkyl/aryl/-azabicyclo
[3.3.1] nonanes have been synthesized, purified and char-
acterized with the help of their analytical and spectral (IR,
40
S by making use of appropriate 2,4-dicarboethoxy-cyclo-
NH hexanone, formaldehyde and appropriate primary amines
N
OH ] by the bis-Mannich condensation reaction. The required
3-aryl-2, 4-dicarboethoxy-5-hydroxy-5-methylcyc
lohexanones have been also synthesized from appro-
priate aldehydes and the ethylactoacetate by the MWI
method as well as, for the first time. The synthesized
H2
C
compound was screened for their analgesic,
NH antihistaminic, local anesthetic and anti-inflammatory
N
OH
activities by standard methods. Some of the compounds
found to exhibit good anti-inflammatory local anesthetic
and antihistaminic activities, in comparison with the stan-
dards employed.
IV
B32 Synthesis and Characterization of a b-
glucoside Conjugate of Doxorubicin
for Application in ADEPT and/or PMT
D. H. Krishna*, D. R. Krishna, N.Raghavender,
Y.Venkateshwarlu, C. E. Mueller, A.R.Rao.
Anthracycline antibiotics, particularly doxorubicin
and daunorubicin, have been used extensively in the
treatment of human malignancies. However cardiotoxicity
and multidrug resistance are significant problems that
limit the clinical efficacy of such agents. Rational design
to avoid these side effects includes strategies such as
drug targeting and prodrug synthesis. Ideally, the activation
of a prodrug should be restricted to the required site of
action, the tumor cell.
Several cancerous tissues and tumors are rich in
certain lysosomal enzymes as compared to those found
in the normal tissues. Thus, a prodrug can be designed
to selectively target such tumor cells where it can be
activated to antineoplastic agent. This approach protects
the normal cells from the cytotoxic effects of the drug. In
this context, a large number of prodrugs have recently
been developed that can be transformed into active
anticancer drugs by enzymes of both mammalian and
nonmammalian origin. However, further investigations
were not undertaken to introduce these prodrugs for
clinical use.
In this regard, the combination of prodrugs with tu-
mor-specific enzymes for use as therapeutic agents was
reported by Connors and re-emphasized in the case of an-
titumor drugs by Bagshawe and Senter, who termed the
approach “antibody-directed enzyme prodrug therapy
(ADEPT)”. In this strategy, the antibody-enzyme conjugate is
first injected and localized at the tumor cell surface antigen.
Subsequently, the nontoxic prodrug is administered , and
the cytotoxic species is released on the tumor cell surface.
We present here a doxorubicin prodrug (1) that is
activated by b-glucosidase.The approach is based on
the use of certain para-substituted benzyloxycarbonyl
groups as bioreversible amine protecting agents. These
agents function as a spacer between glucose and
anthracycline moieties. Only after enzymatic cleavage did
spontaneous self decomposition of this spacer occur to
release the drug (3).
56th IPC Kolkata - Scientific Oral Presentations - Medicinal Chemistry