SYNTHESIS, PHARMACOLOGICAL EVALUATION AND BIOLOGICAL ACTIVITY OF

SOME NOVEL THIADIAZOLE DERIVATIVES

SYNOPSIS FORM.PHARM DISSERTATION

SUBMITTED TO

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES BANGALORE, KARNATAKA

BY

VIJAYALAKSHMI S

I M.PHARM (2010-11)

DEPARTMENT OF PHARMACEUTICAL CHEMISTRY

M.S. RAMAIAH COLLEGE OF PHARMACY

BANGALORE-560054

1

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, BANGALORE, KARNATAKA

ANNEXURE II

PROFORMA FOR REGISTRATION OF SUBJECTFOR DISSERTATION

1. NAME OF THE CANDIDATE AND ADDRESS

VIJAYALAKSHMI S,D\O Sudarshan Sinha, 501/32 , 3rd Main Road, Milk colony, Rajajinagar 2nd Stage, Bangalore, Karnataka. PIN-560055.

2. NAME OF INSTITUTION M.S.RAMAIAH COLLEGE OF PHARMACY,M.S.R.I.T. Post, M.S.R. Nagar, Bangalore-560054

3. COURSE OF THE STUDY AND SUBJECT

M.PHARM PHARMACEUTICAL CHEMISTRY

4. DATE OF ADMISSION 06/07/2010

5.

TITLE OF THE TOPIC

Synthesis, pharmacological evaluation and biological activity ofsome novel thiadiazole derivatives

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6. BRIEF RESUME OF THE INTENDED WORK

6.1 NEED FOR THE STUDY

Drug resistance is a steadily increasing process that is reaching alarming level in the

treatment of infectious diseases caused by pathogenic bacteria, fungi, parasites and viruses.

Over the past few decades, steadily increasing drug resistance in the treatment of infectious

disease pose a serious problem in antimicrobial therapy and necessitates continuing

research into novel classes of antimicrobials.1

Heterocycles, the largest classical division of organic chemistry are of immense

importance biologically, industrially and indeed to the functioning of any developed human

society. The development of simple, facile and efficient synthetic methods for the synthesis

of five-membered heterocycles is one of the major challenges in organic synthesis.2

Five membered heterocyclic compounds show various types of biological activities,

among them 2,5-disubstituted 1,3,4-thiadiazoles are associated with diverse biological

activities, probably by the virtue of -N=C-S- grouping.3

A glance at the standard reference works shows that more studies have been carried

out on the 1,3,4 Thiadiazole than all the other isomers combined. Members of this ring

system have found their way in to such diverse applications as pharmaceuticals, oxidation

inhibitors, cyanide dyes, and metal complexing agents.4

The thiadiazole drugs were the first effective chemotherapeutic agents to be

employed systematically for the prevention and cure of bacterial infection in human beings.

They are also choice for the drug as diuretic (e.g. Acetazolamide).5

1, 3, 4-thiadiazoles possesses various biological activities such as anti-

inflammatory5,6, antihypertensive6, hypoglycaemic6,7, carbonic anhydrase inhibitor, plant

growth regulator, agrochemicals7, antibacterial7,8, antifungal7,8, anti-histaminic9,

anticancer6,10 and anticonvulsant activities.3,11-15

Furthermore, widely explored thiadiazoles are in clinical trials for the treatment of

patients with different tumors.16

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A large number of 1,3,4-thiadiazoles have been patented in the agricultural field as

herbicides, fungicides and bactericides.17,18

It has also been recently reported that some 3-methyl or benzyl 1,2,4-triazolo[3,4-b]

[1,3,4]thiadiazole derivatives are endowed with anti-HIV-1 activity at subcytotoxic

concentrations.19

Pyrazolidinedione moiety has been found to possess antibacterial, anti-

hypertensive, diuretic, analgesic, anti-cancer20 and anti-convulsant21 properties

The therapeutic importance of these rings prompted us to synthesize and evaluate

novel heterocyclic compounds incorporating thiadiazole with pyrazolidinedione moiety to

obtain better anti-inflammatory, anti-convulsant, antifungal and antibacterial activities.

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6.2 REVIEW OF LITERATURE

Synthesis, characterization and biological evaluation of some novel 2,5-disubstituted 1,3,4-thiadiazoles for their potential Antimicrobial activity was reported.1

Synthesis and bioassay of oxazolyl/thiazolyl selenadiazoles, thiadiazoles and diazaphospholes were reported.2

Synthesis and Anticonvulsant activity of substituted oxadiazole and thiadiazole derivatives were reported.3

Recent advancements in the synthesis and pharmacological evaluation of substituted 1, 3, 4- thiadiazole derivatives were reported.4

The in vitro Anti-denaturation effects induced by synthetic products in bovine serum albumin is proposed as a screening assay for the detection of Anti-inflammatory compounds without the use of animals were reported.5

Synthesis and evaluation of Anti-inflammatory activity of 3-chloro-1-[5-(2-hydroxy phenyl)-1,3,4-thiadiazolo-2-yl]-4-substituted azetidin-2-one derivatives were reported.6

Synthesis, characterization and Antimicrobial activity of 2-(2'-substituted - benzylidene - hydrazino -acetyl) – mercapto -5-methyl - 1, 3, 4- thiadiazoles and 2 -[2'- {4 - substituted -aryl - 3 - chloro - 2 - oxo –azetidine } –acetyl-aminomercapto]- 5-methyl - 1, 3, 4 –thiadiazoles were reported.7

Synthesis and Antimicrobial study of bis-[thiadiazol-2-yltetrahydro- 2H-pyrazolo[3,4-d][1,3]thiazole]methanes were reported.8

Pharmacological screening of some new 2(substituted acetyl) amino-5-alkyl- 1. 3, 4-thiadiazoles were reported.9

6-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]-3- [(2-naphthyloxy)methyl][1,2,4]triazolo[3,4-b][1,3,4]- thiadiazole as a potent Antioxidant and an Anticancer agent induces growth inhibition followed by apoptosis in HepG2 cells were reported.10

Synthesis of aromatic aldehyde imine derivatives of 2-thiobenzyl-1,3,4-thiadiazole and evaluation of their Anticonvulsant activity was reported.11

Synthesis of some new N-[4-acetyl-4,5-dihydro-5-(1-aryl-5-methyl-1H-1,2,3-triazol-4-yl)-5-methyl-1,3,4-thiadiazol-2-yl]acetamide derivatives were reported.12

Synthesis, Anticonvulsant and Muscle relaxant activities of substituted 1,3,4-oxadiazole, 1,3,4-thiadiazole and 1,2,4-triazole was reported.13

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Some novel 2-methyl-3-(1'3'4'-thiadiazoyl)-4-(3H)quinazolinones with Anticonvulsant and CNS depressant activity was reported.14

Synthesis of newer indoyl thiadiazoles and their thiazolidinones and formazans as potential Anticonvulsant agents were reported.15

Synthesis and Antioxidant activity of novel ketone hydrazones bearing 5-(Pyridine-3-yl)-1,3,4-thiadiazole was reported.16

Synthesis and biological screening of some halogenated thiadiazoles and triazoles were reported.17

Synthesis and bioactivity study of 2,5-bismercapto-1,3,4-thiadiazole heterocylic derivatives were reported.18

A convenient, rapid microwave assisted synthesis of some novel 3-[(4-chloro-3-methylphenoxy)methyl]-6-aryl- 5,6-dihydro-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles using acidic alumina was reported.19

Synthesis and Antimicrobial evaluation of new isoxazole and pyrazole derivatives were reported.20

Anticonvulsant activity of 1-alkyl-4-substituted 3,5-pyrazolidinediones.21

Synthesis, characterization, invitro Antibacterial, Anti-inflammatory evaluations of novel 4-Quinolone containing pyrazolidinedione derivatives were reported.22

Synthesis and biological studies of some new thiadiazolo[2,3-a] 1,2,4-triazin-5-ones were reported.23

Synthesis and Molluscicidal activity of 2-aryloxymethyl-5-aryl-6-thioxo-[1,2,4]-triazolo-[3,2-b] [1,3,4] thiadiazoles were reported.24

Synthesis and biological activity of 2-arylamino-1,3,4-thiadiazoles were reported.25

Synthesis of some new N-[4-acetyl-4,5-dihydro-5-(1-aryl-5-methyl-1H-1,2,3-triazol-4-yl)-5-methyl-1,3,4-thiadiazol-2-yl]acetamide derivatives were reported.26

Microwave assisted synthesis and biological activity of novel coumarinyltriazolothiadiazoles were reported.27

Synthesis, characterization and biological activity of schiff bases of 2, 5- dimercapto-1,3,4-thiadiazole were reported.28

Synthesis and Antibacterial activity of some new 1,3,4-oxadiazole and 1,3,4- thiadiazole derivatives were reported.29

Synthesis of azetidinonyl substituted 1, 3, 4-thiadiazole-2-yl derivatives as Antibacterial activity was reported.30

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Conventional and greener approach for the synthesis of some novel substituted -4-oxothiazolidine and their 5-Arylidene derivatives of 2-methyl-benzimidazole: Antimicrobial activities were reported.31

Synthesis, characterization and Anti-microbial activity of fluoro benzothiazole incorporated with 1,3,4-thiadiazole was reported.32

Synthesis, characterization and Antimicrobial activity evaluation of new 2,4-Thiazolidinediones bearing imidazo[2,1-b][1,3,4]thiadiazole moiety was reported.33

Synthesis and crystal structure of some 3,5-pyrazolidinediones were reported.34

Synthesis and evaluation of some substituted thiadiazoles as antidiabetic agents were reported.35

Synthesis and Antibacterial activity of some triazolothiadiazines and triazolothiadiazoles incorporating tetrahydrocarbazole moiety was reported.36

Synthesis of 2-amino-1,3,4-thiadiazoles were reported.37

Synthesis and Antimicrobial evaluation of 3-methoxy-5-nitro-2-(1,3,4-oxadiazolyl,1,3,4-thiadiazolyl and 1,2,4-triazolyl)benzofurans were reported.38

Synthesis of pharmaceutically important 1,3,4-thiadiazole and imidazolinone derivatives as Antimicrobials were reported.39

Synthesis, Antimicrobial and Antioxidant activities of sulfone linked bis heterocycles—pyrazolyl oxadiazoles and pyrazolyl thiadiazole was reported.40

Synthesis, characterization and Antimicrobial activity of metal chelates of 5-[4-chloro phenyl(1, 3, 4)thiadiazol-2-ylamino methylene]-8-hydroxy quinoline was reported.41

Synthesis, characterization and Antimicrobial activity of azol substituted derivatives were reported.42

Synthesis of new polymers derived from poly (vinyl Chloride) and study their biological evaluation was reported.43

Synthesis and Anti-Inflammatory activities of novel salicylic acid and diflunisal amide derivativewere reported.44

2, 4- Di substituted-5-imino-1, 3, 4- thiadiazole derivatives: Synthesis and biological evaluation of Anti-inflammatory activities were reported.45

Synthesis and biological evaluation of some 1, 3, 4-thiadiazoles were reported.46

Synthesis and in vitro Anti-helicobacter pylori activity of 2-(substituted benzylthio)-5-(5-nitro-2- furyl)-1, 3,4-thiadiazole derivatives were reported.47

7

Synthesis and biological activity of some new 1,3,4-thiadiazole and 1,2,4-triazole compounds containing a phenylalanine moiety was reported.48

Synthesis and characterization of metal complexes of Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Ru(III), Rh(III) and Pd(II) with derivatives of 1,3,4-thiadiazole-2, 5-dithiol as new ligands were reported.49

Inhibition of growth of Leishmania donovani promastigotes by newly synthesized 1,3,4-thiadiazole analogs were reported.50

Synthesis and biological activity of some new thiadiazole derivative was reported.51

Synthesis and crystal structure of 3-benzyl-6-trichloromethyl-[1,2,4] triazolo[3,4-b][1,3,4]thiadiazole was reported.52

Synthesis and biological activity of some 2-[3-substituted-2-thione-1,3,4-thiadiazole-5-yl]aminobenzothiazoles were reported.53

Synthesis of new triazolo-thiadiazoles and their Antimicrobial activity was reported.54

Synthesis and biological screening of 5-{[4,6-disubstituted pyrimidine-2-yl)thio]methyl}-N-phenyl-1,3,4-thiadiazol-2-amines were reported.55

Synthesis and Antibacterial activity of 6-(5-phenyl-[1,3,4]thiadiazol-2-ylamino)-benzopyran-2-ones were reported.56

Synthesis of some new 5-[2-{(1,2,3-benzotriazole)-1-yl-methyl}-1'-(4'-substituted aryl-3'-chloro-2'-oxo azetidine)]-amino-1,3,4-thiadiazoles: Antifungal and Antibacterial agents were reported.57

Synthesis and QSAR studies of thiosemicarbazides, 1,2,4-triazoles, 1,3,4-thiadiazoles and 1,3,4-oxadiazoles derivatives as potential Antibacterial agents were reported.58

Synthesis, characterization and pharmacological studies on some triazolothiadiazines and triazolothiadiazoles containing naphtha[2,b]furan was reported.59

Synthesis and study of some newer analogues of Quinolin-8-ol as potent Antimicrobial agents were reported.60

Synthesis and biological studies of bis (thiadiazole/triazole) by sonication was reported.61

Synthesis and Antimicrobial activities of 1,2,4-triazole and 1,3,4-thiadiazole derivatives of 5-amino-2-hydroxybenzoic acid was reported.62

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Synthesis of symmetrical and unsymmetrical 1,3,4-oxadiazoles and their interconversion to 1,3,4-thiadiazoles and 1,2,4-triazoles were reported.63

Synthesis and characterization of novel azole heterocycles based on 2,5-disubstituted thiadiazole was reported.64

Synthesis and free radical scavenging activity of some 1,3,4-thiadiazole derivatives were reported.65

Synthesis and characterization of some alkoxyphthalimide derivatives of benzotriazolylthiadiazoles and benzotriazolylthiazolidinones were reported.66

Synthesis and Fungicidal activity of some 3-(5-aryl-1,3,4-thiadiazol-2-yl)-1-(β-D-glucopyranosyl)-5-alkyl-2-thio-4-imidazolidinones were reported.67

Microwave-assisted synthesis and biological activity of 3-alkyl/aryl-6-(1-chloro-3,4-dihydronaphth-2-yl)-5,6-dihydro-s-triazolo[3,4-b] [1,3,4]thiadiazoles were reported.68

Synthesis of substituted steroidal thiadiazole, triazole and oxidotriazole was reported.69

Synthesis, crystal structure and bioactivities of 1-(4-chlorophenyl)-3-[5-(pyrid-4-yl)-1,3,4-thiadiazol-2-yl]urea was reported.70

Synthesis, Antimicrobial, and Anti-inflammatory activities of novel 2-(1-adamantyl)-5-substituted-1,3,4-oxadiazoles and 2-(1-adamantylamino)-5-substituted-1,3,4-thiadiazoles were reported.71

Synthesis and Antibacterial activity of N-[5-(chlorobenzylthio)-1,3,4-thiadiazol-yl] piperazinyl quinolone derivatives were reported.72

Convenient synthesis of some triazolothiadiazoles and triazolothiadiazines carrying 4-methylthiobenzyl moiety as possible Antimicrobial agents were reported.73

Synthesis of 2-(isoquinolinemethylidene)-1,3,4-thiadiazole derivatives were reported.74

Synthesis and Antimicrobial activity of some new 1,3,4-thiadiazole and 1,2,4-triazole compounds having a D,L-Methionine moiety was reported.75

Synthesis and biological activity of some novel derivatives of 4-amino-3-(D-galactopentitol-1-yl)-5-mercapto-1,2,4-triazole was reported.76

Synthetic studies on the synthesis of some new fused heterocyclic compounds derived from 3,5-pyrazolidinedione was reported.77

Pyrazolidinedione derivatives were reported.78

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Synthesis and Antimicrobial activity of novel 2-methyl-3-(1'3'4'-thiadiazoyl)-4-(3H) quinazolinones were reported.79

Synthesis of some novel 4-substituted coumarins having potential biological activity ( Part III ) was reported.80

Synthesis, characterization and biological studies of some triazolothiadiazines and triazolothiadiazoles containing 6-chloropyridin-3-yl methyl moiety was reported.81

Green synthesis of substituted imidazothiadiazoles using ionic liquid was reported.82

Microwave promoted efficient synthesis of 2,5-disubstituted 1,3,4-thiadiazole was reported.83

Conventional and ultrasound mediated synthesis of some thiadiazoles, triazoles and oxadiazoles were reported.84

Synthesis and Antituberculosis activity of 2-(aryl/alkylamino)-5-(4-aminophenyl)-1,3,4-thiadiazoles and their Schiff bases were reported.85

Synthesis and biological activity of new 1,3,4-thiadiazole derivatives.86

Synthesis and pharmacological evaluation of 2-(3',5'-dichlorobenzo[b]thiophen2'-yl)-5-arylamino-1,3,4-thiadiazoles were reported.87

Design, synthesis and pharmacological evaluation of new nonsteroidal Antiinflammatory 1,3,4-thiadiazole derivatives were reported.88

Synthesis of 1,3,4-thiadiazole, 1,3,4-thiadiazine, 1,3,6-thiadiazepane and quinoxaline derivatives from symmetrical dithiobiureas and thioureidoethylthiourea derivatives were reported.89

Phase transfer catalyzed synthesis and Antibacterial activity of water-soluble S-triazolo[3,4-b][1,3,4]thiadiazoles containing piperazine group was reported.90

Synthesis of thiazo- or thiadiazo- naphthalene carboxamides via mercuric intermediates and their Antitumor and DNA photocleavage activities were reported.91

Synthesis of some new thiosemicarbazide and 1,3,4- thiadiazole heterocycles bearing benzo[b]thiophene nucleus as a potent Antitubercular and Antimicrobial agents were reported.92

Synthesis of some novel 3,6-Bis(1,2,3-triazolyl)-s-triazolo[3,4-b]-1,3,4-thiadiazole derivatives were reported.93

The synthesis of 2-(chromon-2/3-yl)-3-(5-thione-4-hydro-1,3,4- thiadiazol-2-yl)-4-oxo-thiazolidine was reported.94

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Synthesis of thiadiazoles and 1,2,4-triazoles derived from cyclopropane dicarboxylic acid was reported.95

Synthesis and biological activities of some 1,3,4-oxadiazoles, thiadiazoles, triazoles and related compounds possessing benzofuran moiety was reported.96

Synthesis and Antinociceptive Activity of 2-[(2-Oxobenzothiazolin-3-yl)methyl]-5- aminoalkyl/aryl-1,3,4-thiadiazole was reported.97

Synthesis of new fused and spiro heterocyclic systems from 3,5-pyrazolidinediones were reported.98

Synthesis and biological activity of 3-(2-furanyl)-6-aryl-1,2,4- triazolo[3,4-b]-1,3,4–thiadiazoles were reported.99

Thiazolylmethylene-3,5-pyrazolidinedione dye-donor element for thermal dye transfer was reported.100

Chemical electrochemical mechanism. Electrochemical reduction of some pyrazolidine-3,5-diones in DMSO. Relation between voltammetric behavior and 1H nuclear magnetic resonance spectra was reported.101

Pyrazolidines in the Treatment of Gout was reported.102

Pyrazolidine-3,5-dione derivatives were reported.103

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6.3 OBJECTIVES OF STUDY

1) To synthesize the proposed derivatives with optimum yield.

2) To purify the synthesized compounds.

3) To characterize the synthesized compounds by Spectral interpretation and by means of chemical tests.

4) To evaluate the anti-microbial, anti-fungal, anti-inflammatory and anti-convulsant activity of the synthesized compounds.

7. MATERIAL AND METHODS

7.1 SOURCE OF DATA

1) Chemical abstracts, Tetrahedron, websites.

2) Journals and publications.

3) Lab based studies.

7.2 METHODS OF COLLECTION OF DATA

PRE-LABORATORY AND LABORATORY WORK

1) PRE-LABORATORY WORK

The chemicals & reagents required for the synthesis and evaluation of the proposed

compounds will be procured from reputed chemical suppliers like Merck, Ranbaxy,

Qualigens, Himedia, S.D Fine Chemicals, Spectrochem, etc.

2) LABORATORY WORK

A) SYNTHESIS

Conventional methods of synthesis will be attempted. The completion of the

reaction will be determined by TLC, IR. Advantages and feasibility of the methods

will be analyzed.

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B) PURIFICATION AND PHYSICAL CONSTANTS

The synthesized compounds will be purified by different methods like fractional

crystallization, recrystallization, distillation and chromatographic methods. The

purity will be ascertained by TLC, IR, NMR, Mass Spectroscopy. The physical parameters like solubility in various solvents, melting point or boiling

point, nature of the crystals, color and percentage of yield will be obtained after the

purification by recrystallizing in a suitable solvent.

C) CHARACTERIZATION

The synthesized compounds will be characterized by:

1. Chemical tests for important functional groups.

2. Study of spectral data.

D) PHARMACOLOGICAL STUDIES

IN-VIVO :

A CUTE TOXICITY STUDY : 95

The study will be carried out as per the guidelines set by OECD. After

administration of the dose, the animals will be observed continuously for the first three

hours, for any toxic manifestation like increased motor activity, salivation, acute

convulsion, coma and death. The animals will be continuously observed for mortality

and behavioral responses for 48 hrs and thereafter daily for 14 days after

administration. The 1/10th of the lethal dose will be taken as effective dose ED50

(therapeutic dose).

Total number of animals required in this model: 192

SCREENING OF ANTICONVULSANT ACTIVITY: 11-15

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The anticonvulsant activity of each test compound will be evaluated by

Maximal Electroshock Seizure Model. The anticonvulsant screening will be performed

using male and female albino mice (18-22g).

Total numbers of groups are 10 (each group containing 6 mice).

Group I (control group) : Electric shock (150mA current for 0.2 sec)

Group II (standard) : Phenytoin (25mg/kg body weight, i.p) +

Electric shock (150mA current for 0.2 sec)

Group III : Derivative I + Electric shock (150mA current for 0.2 sec)

Group IV : Derivative II + Electric shock (150mA current for 0.2 sec)

Group V : Derivative III + Electric shock (150mA current for 0.2 sec)

Group VI : Derivative IV + Electric shock (150mA current for 0.2 sec)

Group VII : Derivative V + Electric shock (150mA current for 0.2 sec)

Group VIII : Derivative VI + Electric shock (150mA current for 0.2 sec)

Group IX : Derivative VII + Electric shock (150mA current for 0.2 sec)

Group X : Derivative VIII+ Electric shock (150mA current for 0.2 sec)

Total number of animals required in this model: 60

MES-convulsion electric shock will be applied through the ear electrodes (150mA

current for 0.2 sec). Time (sec) in various phases of convulsion (Flexion, Extensor,

Clonus, Stupor) and Recovery/Death will be observed.

Statistical Analysis: Results of the study will be subjected to statistical analysis by

One Way ANOVA followed by Tukey Kramer Multiple Comparison Test.

SCREENING OF IN-VITRO ANTI-INFLAMMATORY ACTIVITY: 21

This will be carried out by dissolving minimum amount of test compounds in

dimethyl formamide (DMF) and diluted with phosphate buffer (0.2M, ph 7.4). Final

solution of DMF in all solutions will be less than 2.5%. Test solution (1ml) containing

different concentrations of synthesized compounds will be then mixed with 1ml of

1mg/ml albumin solution in phosphate buffer and incubated at 27±1ºC for 15 min.

Denaturation will be induced by keeping the reaction mixture at 60±1ºC in water bath

for 10-20 min. Later after cooling the turbidity will be measured at 660nm in U.V

14

spectrophotometry. The percentage inhibition of denaturation will be calculated from

control where no synthesized compounds will be added and compared against

Ibuprofen(standard).

SCREENING OF ANTIBACTERIAL ACTIVITY BY DISC DIFFUSION

METHOD:12,24,28

This will be carried out on both Gram positive and Gram negative organisms like

Staphylococcus aureus, pseudomonas aeruginosa, Escherichia coli, Bacillus subtilis etc

using sterile Media like Mueller-Hinton Agar etc by Disc Diffusion Method. Zone of

inhibition of the compounds synthesized will be noted and compared with that of

standard drugs like Amoxicillin, Ciprofloxacin etc.

SCREENING OF ANTIFUNGAL ACTIVITY BY DISC DIFFUSION

METHOD:12,24,28

This will be carried out on organisms like Candida albicans and Aspergillus niger

using Media like Sabouraud Dextrose Agar by Disc Diffusion Method. Zone of

inhibition of the compounds synthesized will be compared with that of standard drugs

like griseofulvin. The entire work will be done using Horizontal Laminar Flow hood.

7.3 DOES THE STUDY REQUIRE ANY INVESTIGATION OR INTERVENTIONS

TO BE CONDUCTED ON PATIENTS OR OTHER HUMANS OR ANIMALS?

Yes, animal experiments on mice will be required for studying anti-convulsant

activity.

7.4 HAS ETHICAL CLEARANCE BEEN OBTAINED FROM YOUR

INSTITUTION IN CASE OF 7.3?

“Yes”

(Certificate Enclosed)

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of 3-chloro-1-[5-(2-hydroxy phenyl)-1,3,4-thiadiazolo-2-yl]-4-substituted azetidin-2-

one derivatives. Indian Drugs May 2010;47(5):11-16.

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6-[3-(4-Fluorophenyl)-1H-pyrazol-4-yl]-3-[(2-naphthyloxy)methyl]

[1,2,4]triazolo[3,4-b][1,3,4]- thiadiazole as a potent antioxidant and an anticancer

agent induces growth inhibition followed by apoptosis in HepG2 cells. Arabian

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thiobenzyl-1,3,4-thiadiazole and evaluation of their anticonvulsant activity. Indian J.

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disubstituted 1,3,4-thiadiazoles:pharmacophore model studies. Acta Poloniae

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9. SIGNATURE OF THE STUDENT :

10. REMARK OF THE GUIDE : Recommended for registration

11. NAME AND DESIGNATION:

11.1 GUIDE : Mrs. B.V. SUMA ASST. PROFESSOR Department of Pharmaceutical Chemistry M.S. Ramaiah College of Pharmacy Bangalore-560054

11.2 SIGNATURE :

11.3 CO-GUIDE : Not Applicable

11.4 SIGNATURE : Not Applicable

11.5 HEAD OF THE DEPARTMENT : Prof. C.H.S. VENKATARAMANA

Professor and HOD (In-charge) Department of Pharmaceutical Chemistry

M.S.Ramaiah College of Pharmacy Bangalore-560054

11.6 SIGNATURE :

12. 12.1 REMARK OF THE PRINCIPAL :

12. 12.2 SIGNATURE OF THE PRINCIPAL :

27

28