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J Pharm Chem Biol Sci , September-November 2015; 3(3):329-345

Journal of Pharmaceutical, Chemical and Biological

Sciences ISSN: 2348-7658

Impact Factor (GIF): 0.615 Impact Factor (SJIF): 2.092

September-November 2015; 3(3): 329-345

A Review on Various Biological Activities of 1,3,4- Thiadiazole Derivatives

Lincy Joseph1, Mathew George1, Prabha Mathews1*

1Department of Pharmaceutical Chemistry, Pushpagiri College of Pharmacy, Thiruvalla- 689107, Kerala, India 2Department of Pharmacology, Pushpagiri College of Pharmacy, Thiruvalla- 689107, Kerala, India *Corresponding Author: Prabha Mathews, Department of Pharmaceutical Chemistry, Pushpagiri College of Pharmacy, Thiruvalla- 689107, Kerala, India Received:23 August 2015 Revised:01 September 2015 Accepted:06 September 2015

INTRODUCTION

The biological activity of compounds mainly

depends on their molecular structure.

Heterocyclic moieties can be found in a large

number of compounds which display large

number of biological activity. Thiadiazole is a

versatile moiety that exhibits a wide variety of

activity due to the presence of N=C-S moiety in

the ring. They have become an important class

of heterocycles of great interest of researches

because of their broad types of biological

activity. Many drugs containing 1,3,4-

thiadiazole nucleus like acetazolamide(1),

butazolamide(2),

Review Article

ABSTRACT

Large number of studies has been repoted on1,3,4- thiadiazole and their derivatives because of their

wide range of biological activities. They are found to have antibacterial, anti inflammatory, anticancer,

anti diabetic, anti convulsant, anti tubercular activities. Many drugs containing thiadiazole derivatives

are available in market such as acetazolamide, methazolamide, sulphamethazole, cefazoline. The

synthesis of novel thiadiazole derivatives and investigation of their chemical and biological activities

have gained more importance. Modification of the thiadiazole ring has proven highly effective with

improved potency and lesser toxicity. This review article highlights the recently synthesized

thiadiazole possessing important biological activities.

Keyword: 1,3,4- Thiadiazole; antimicrobial activity; anti inflammatory activity; anti diabetic activity; anti

cancer activity; antitubercular activity; anti convulsant activity; antioxidant activity

Joseph et al 330

J Pharm Chem Biol Sci , March-May 2015; 3(1):329-345

sulfamethazole(3) are available in market. In

addition other analogues have found to be used

as dye, pesticides, lubricants and conducting

polymers [1]. N N

SAcHNSO2NH2

(1)

N N

S SO2NH2

NH

OCH3

(2)

N

S

N

CH3

NHS

OO

NH2 (3)

In the present review, emphasis on the

biological activities of substituted 1,3,4-

thiadiazole and structurally related thiadiazoles.

CHEMISTRY

Thiadiazole is an important five membered

heterocyclic ring containing two nitrogen atoms

and a sulphur atom as hetero atoms with the

general formula of C2H2N2S. They occur in four

isomeric forms namely 1, 2, 3-thiadiazole,

1,2,4 thiadiazole, 1,2,5- thiadiazole, 1,3,4-

thiadiazole. Among them 1, 3, 4 thiadiazole ring

exhibits more versatile activities.

NS

N

1,2,3-thiadiazole

NS

N

1,2,4-thiadiazole

NS

N

1,2,5- thiadiazole

S

N N

1,3,4-thiadiazole

The ring system is less aromatic than benzene,

thiophene, and pyridine. The aromatic

character is measured by π electron

delocalization which decreases in the order 1, 2,

5 thiadiazole>thiophene>thiazole>1, 3, 4-

thiadiazole2. The electron withdrawing nature

of the nitrogen atoms ensures that electrophilic

attack at carbon is very rare and nucleophilic

substitution reactions are common.

Electrophilic attack at the sulphur atom has

been observed. 1, 3, 4 – thiadiazoles are weak

base due to the inductive effects of extra

hetero atoms and are readily alkylated and

acylated at N3 [1]. The ring is relatively stable in

aqueous acid solutions but the ring gets cleaved

in aqueous basic solutions. 1, 3, 4-thiadiazole

core skeletons are subjected to various

substitution reactions with alkyl halides, acid

chlorides, and sulfonyl chlorides to afford

various drug like 2-amino-substituted 1, 3, 4-

thiadiazole derivatives [3]. When substituents

are introduced into 2’ or 5’ position of this ring,

the ring is highly reactive and forms different

derivatives of thiadiazole easily.

The reactivity of ring nitrogen atom arises from

electrophilic reactions depending on tautomeric

equilibrium of thione-thiol or amine-imine. In

thione or imine form deprotonation of ring N-H

can take place and ring nitrogen atom becomes

vulnerable to alkylation or acylation or

transformation to 1,3,4 –thiadiazolium salt. The

reactions are conducted with electrophiles such

as alkyl halides, trimethylsilylmethyl trifluoro

methanesulfonate, formaldehyde [4] etc.

Joseph et al 331


Tautomerism exhibited by thiadiazole is as follows:

X = -SH, -NH2

X' = -S, -NH

Few examples for electrophilic substitution on

ring nitrogen is as follows [4]:

1. Alkylation by methyl halides (always iodides

and bromides) were frequently reported to

produce 3-methyl- 1, 3, 4- thiadiazoles in

aprotic solvents such as DMF in the presence of

K2CO3

2. When amino thiadiazole is treated with

bromo ethanol solution hydroxyl alkyl

thiadiazoles are formed.

S

N N

R NH2 BrCH2CH2OH

Reflux, 3h

S

N N

R1 NH HBr

CH2CH2OH

3. When treated with formaldehyde in the

presence of ethanol and acetic acid forms

hydroxyl methyl derivatives.

S

N NH

RS SCH2O, EtOH

Acetic acid

S

N N

RS S

CH2OH

BIOLOGICAL ACTIVITIES OF 1, 3, 4-

THIADIAZOLE DERIVATIVES

Remarkable progress has been made in the

development of thiadiazole derivatives in the

recent years and the most recent studies have

revealed that of thiadiazole derivatives has a

wide spectrum of pharmacological properties

like anticancer, antitubercular, antimicrobial,

antidiabetic, antioxidant, anti-inflammatory,

anticonvulsant, diuretic activities. Following are

some of the examples of biological activities of

thiadiazole derivatives.

S

N N

R1 R

2

+ CH3I

S

N N+

R1 R

2

CH3

+

S

N+

N

R1 R

2

CH3

Joseph et al 332


Antimicrobial activity

Mahendrasinh M Raj [5] et al synthesized

thiadiazole derivatives by the reaction

between benzoic acid 2-hydroxy benzoic acid

with thiosemicarbazide using conc. H2SO4 as

oxidising agent. The synthesized compounds

were characterized by IR. H1NMR and

nitrogen estimation and screened for their

antibacterial and antifungal activities by

paper disc diffusion technique. All the

synthesized compounds showed moderate

activity against bacteria and fungi.

O OH

R

+S

NHNH2

NH2

conc. H2SO4

Ethanol

N

S

N

NH2

R

Carboxylic acid R= H, OH

THiosemicarbazide5

- phenyl

-1, 3, 4

- thiadiazole

Arun Kumar [6] et al synthesized thiadiazole

from thiosemicarbazide. Thiosemicarbazide

derivative on cyclisation with different

aromatic carboxylic acids in the presence of

POCl3 formed 1, 3, 4 thiadiazole derivatives

which were characterized by elemental

analysis, IR, H1NMR and Mass spectral data’s

and screened for their antimicrobial activities

and showed significant antimicrobial

activities.

N

SCl

NH2

CS2, C2H5OH

NH2NH2, H2O

N

SCl

NH

S

NH

NH2

RCOOH

POCl3

N

SCl

NH

S

N

N R

Guanghui Zong [7] et al synthesized a series

of novel glycosyl thiadiazole derivatives were

designed and synthesized by condensation of

sugar aldehydes and substituted

thiosemicarbazide followed by oxidative

cyclization by treating with manganese

dioxide. Compounds exhibited excellent

fungicidal activities.

Joseph et al 333


O

OH

OHOH

OH

OH

O

OR

OHC

O

O

CH3

CH3

O

OR1

CH

O

O

CH3

CH3

NNHNH

NH

S

R2 CHCl3

MnO2O

OR1

O

O

CH3

CH3

S

NN

NH

R2

S

NHR

2

NHNH2

CH2Cl2

Sobhi M Gomha [8] et al synthesized some

novel compounds, namely, 3-(2-methyl-1H-

indol-3-yl)-6-aryl-[1, 2, 4] triazolo [3,4-b][1,

3,4] thiadiazoles via bromination of 2-

methyl-3-[4-(arylideamino)-5-mercapto-4H-

[1,2,4triazol-3-yl]-1H indoles. New

thiadiazoles, triazoles and oxadiazoles with

indole moieties were prepared by the

cyclization of corresponding

thiosemicarbazides with microwave

irradiation using different reaction conditions.

The structure of the synthesized compounds

was confirmed by elemental analysis and

spectral analysis. The antibacterial activity of

the newly synthesized compounds against

Staphylococcus aureus, Bacillus subtilis,

(gram-positive) E.coli(gram-negative) and

antifungal activity against Candida albicans

were studied under the same condition using

trimethoprim as reference in Muller-Hinton

agar medium by disc agar diffusion method.

Joseph et al 334


NH

CH3

NN

NSH

N RBr2/ AcOH

NH

CH3

NN

NSH

N R

Br

NH

CH3

NN

N

N

S R

Anti inflammatory activities

Mohammad Asif [9] et al syntheszed 2,4-

diphenyl-5-imino-1,3,4-thiadiazole derivatives

by cyclization of α-chlorobenzal

phenylhydrazone derivatives using potassium

thiocyanate. Α-chlorobenzal phenylhydrazone

derivatives were synthesized by chlorination

of hydrazonyl derivatives using PCl5 which in

turn was synthesized from benzoyl chloride

and phenyl hydrazine in pyridine. The

thiadiazole derivatives synthesized were

characterized by IR, H1NMR and elemental

analysis and screened for in vivo anti-

inflammatory activity by carageenan induced

paw oedema and a few of them showed

promising activity when compared to

standard drug diclofenac sodium.

R1

R2

O

Cl

+

NHNH2

R3

R4

CH3OH

Pyridine

R1

R2

O

NH NH

R4

R3

Benzoyl chloride derivative

Phenyl hydrazine derivative

Hydrazonoyl derivatives

R1

R2

Cl

N NH

R4

R3

Chlorobenzal phenyl hydrazone derivatives

CH3OH

PCl5

R1

R2

S

N

N

NH

R3

R4

2,4- diphenyl 5

-imino

-

2- 1,3,4

-thiadiazoline dreivatives

Shiv K Gupta [10] et al synthesized

disubstituted thiadiazole derivatives by

reaction between salicylic acid and

thiosemicarbazide in presence of conc. H2SO4.

In vivo anti-inflammatory activity was

evaluated and compared with standard drug

ibuprofen and all compounds showed

moderate anti inflammatory activity.

Joseph et al 335


O

OH

OH

+ NH2

NH NH2

S OH

NH NH

S

NH2

H2SO4

N

S

N

NH2

OH

carboxylic acid derivativethiosemicarbazide

thiadiazole derivative

Alok pandey [11] et al synthesized Schiff

bases of 2-amino-5-aryl-1,3,4-thiadiazole

derivatives with different aromatic aldehyde.

1, 3, 4 – thiadiazole derivatives were

prepared by the reaction of

thiosemicarbazide, sodium acetate and

aromatic aldehyde. All the compounds were

evaluated for their analgesic activity against

swiss albino mice, anti inflammatory activity

against wister albino rats, and antibacterial

activity against Staphylococcus and E. coli

bacteria and tubercular activity against

Mycobacterium tuberculosis. All the

synthesized compounds exhibited analgesic,

anti-inflammatory, antibacterial and anti-

tubercular activities act various minimum

inhibitory concentration levels.

CHO

R CH3COONa

R

NNH

S

NH2

CH3COONaBr2/CH3COOH

R

N

S

N

NH2

R

N

S

N

N

CH3

ArCHO

C2H5OH

NH2NHCSNH2

Abhay Kumar Verma [12] et al synthesized N-

phenyl thiosemicarbazide from aromatic

amine by refluxing with CS2 and hydrazine

hydrate in ethanol and from phenyl

isothiocyanate by reacting with hydrazine

hydrate in ethanol. The synthesized

thiosemicarbazides where condensed with

aromatic carboxylic acid in presence of conc.

H2SO4 to form thiadiazole analogues. The

compounds were screened for anti

inflammatory activity by carageenan induced

rat paw edema method and the compounds

exhibited significant to moderate anti

inflammatory activity.

Joseph et al 336


NH2 NSC

anilinephenyl isothiocyanate

NH2

-NH2

C2H5OH

CS2, C2H5OH

NH3, NH2

-NH2

NH NH

NH2

S

DMF

ConcH2SO4

8-12 minutes

O

OH

R

NH S

NN

R

phenyl thiosemicarbazide

Microwave

Anti cancer activity

Arun Naskar [13] et al synthesized 2-amino-5-

aryl -1,3,4- thiadiazoles by oxidative

cyclization of thiosemicarbazones using FeCl3

catalyst and from this Schiff bases were

prepared by condensation with aldehyde and

synthesized compounds were characterized

by IR, NMR, and CHN analysis. Anticancer

activity was evaluated using Ehrlich’s Ascites

carcinoma cells and all the compounds

exhibited significant anticancer activity

compared to control.

CHO

R1

+ NH2

NH NH2

S

-H2O

R1

NNH

S

NH2

Fe3+

Cyclization

N N

SNH2

R1

Ethanol, 6h reflux

CHO

R2

N N

S

N

R1

R2

Joseph et al 337


Suddasatwa Banerjee [14] et al synthesized

thiadiazole derivatives with new amino group

by refluxing furan-2-carboxylic acid with

thiosemicarbazide in presence of conc.H2SO4

and then different Schiff bases were prepared

by reacting with various substituted

aldehydes in presence of few drops of glacial

acetic acid. The structures of the synthesized

compounds were confirmed by spectral

data’s. Screening for in vitro anticancer

activity was carried out using MTT (3-[4,5-

dimethylthiazol-2-yl]-2,5-diphenyl terazolium

bromide) assay on HT-29 colorectal cancer

cell line. The compounds had shown

significant activity at very less concentration.

O

O

OH+ NH2NHCSNH2

Conc. H2SO4, Reflux

C2H5OH

O

N

S

N

NH2

O

R

Ethanol, G.A.A

O

N

S

N

NR

Doaa E. Abdel Rahman [15] et al synthesized

substituted imidazo [2,1-b]-1, 3, 4 –

thiadiazoles , substituted 1, 3, 4-

thiadiazolo[3,2-a] pyrimidines and substituted

thioureas. Structures elucidated by IR, NMR

and Mass spectroscopy. All the compounds

were evaluated for their cytotoxic activity

against tumor cell line A549(non-small cell

lung cancer cell line) using Sulfo-Rodamine B

(SRB) standard method. Most of the tested

compounds exhibited potent cytotoxicity.

Docking studies were performed to explore

the possible binding modes of these

compounds with the binding site of fibroblast

stromelysin-1 enzyme, which is involved in

several pathological conditions including

cancer.

Synthesis of substituted imidazo [2,1-b]-1, 3, 4 – thiadiazoles

Br

N

S

N

NH2

i) phenacyl bromide,dioxane, reflux 5h

saturated sodium acetatesolution

Br

N

S

N

N

R

Joseph et al 338


Synthesis of substituted 1, 3, 4-thiadiazolo[3,2-a] pyrimidines

Br

N

S

N

NH2

malononitrile, triethyl amine

ethanol, refluxBr

N

S

N

N

NH2

NH

Synthesis of thiourea substituted thiadiazole derivative

Br

N

S

N

NH2

RNCS

Ethanol, reflux

Br

N

S

N

NH

NH

RS

Antidiabetic activity

Prasanna A Datar [16] et al designed

thiadiazole compounds as antidiabetic agent

using docking studies. The designed

thiadiazole derivatives are synthesized by

cyclization between aromatic acid and

thiosemicarbazide using conc. H2SO4 and

condensing the product with aldehyde in

presence by microwave irradiation. The

compounds were subjected to antidiabetic

activity by in vitro α amylase inhibitory

method and in vivo method in alloxan

induced diabetes rat model. Molecular

docking revealed that synthesized derivatives

and target proteins were actively involved in

binding and had significant correlation with

biological activity.

ArCOOH + NH2NHCSNH2

H2SO4

-CO2

S

N N

NH2

Ar-

RCHO

Microwave

S

N N

NAr-

R

S. R Pattan [17] et al synthesized thiadiazole

derivatives by cyclization between aromatic

acid and thiosemicarbazide using conc. H2SO4

and Schiff bases of thiadiazole were

synthesized by reacting with various aromatic

substituted adehydes. Structures of the

compounds were established based on

spectral data. All the compounds were

evaluated for antidiabetic activity by alloxan

induced tail tipping method and most of the

compounds showed promising activities.

ArCOOH + NH2NHCSNH2

H2SO4

-CO2

S

N N

NH2

Ar-

RCHO

Microwave

S

N N

NAr-

R

M Sai Harika [18] et al synthesized 5-phenyl-

1,3,4- thiadiazol 2 amine by reacting benzoic

acid with thiosemicarbazide, which on

reaction with different aromatic aldehydes

afforded 5-phenyl-N-[(E)-

phenylmethylidene]-1,3,4-thiadiazol-2-amine

derivatives. The compounds on treatment

with thioglycolic acid in presence of ZnCl2

Joseph et al 339


gave 2-phenyl-3-(5-phenyl-1,3,4-thiadiazol-2-

yl)-1,3- thiazolidin-4-one. The structures of

the compounds were confirmed by spectral

datas. The synthesized compounds were

evaluated for their antidiabetic activity by

alloxan induced rat model using the

parameters like serum glucose, serum

triglycerides, SGOT, SGPT, and body weight

ArCOOH + NH2NHCSNH2

H2SO4

-CO2

S

N N

NH2

Ar-

RCHO

Microwave

S

N N

NAr-

R

SHCH2COOHZnCl2

S

N N

N

S

O

Ar-

Ar-

Anti oxidant activity

Sandeep K Chitale [19] et al synthesized

thiadiazole from aromatic acid and

thiosemicarbazide, and Schiff bases were

prepared by reacting with different aldehydes

and isatin using glacial acetic acid as catalyst.

Elemental analysis, IR, H1 NMR and mass

spectral data elucidated structure of newly

synthesized compounds and tested for in

vitro antioxidant activity by testing nitric

oxide and hydrogen peroxide scavenging

activity. Some of these novel derivatives

showed moderate to potent antioxidant

activity.

ArCOOH + NH2NHCSNH2

Conc. H2SO4

Ethanol

S

N N

NH2

Ar-

RCHO, G.A.A

MicrowaveSN

N

Ar-

N

R

Brijendra Kumar Soni [20] et al synthesized

thiadiazole derivative and evaluated for in

vitro antioxidant activity by hydrogen

peroxide and nitric oxide scavenging activity

and lipid peroxidation inhibitory activity.

Some of the compounds showed potent

antioxidant activity.

ArCOOH + NH2NHCSNH2

Conc. H2SO4

Ethanol

S

N N

NH2

Ar-

RCHO, G.A.A

MicrowaveSN

N

Ar-

N

R

Anticonvulsant activity

Masi Hasmin. H [21] et al designed and

synthesized a series of Carboxamide moiety

with substituted 1,3,4-thiadiazoles. These

title compounds were prepared by

condensation of benzoxazine with 2,5-

disubstituted-1,3,4- thiadiazole . Structure

elucidations of the synthesized compounds

were done by spectral analysis. The

Joseph et al 340


anticonvulsant activity of the title compounds

were evaluated by using PTZ model

(60mg/kg) and carbamazepine taking as a

reference standard (100 mg/kg). All

synthesized compounds showed no sedation

side effect as compared to reference

standard (carbamazepine). Their study

indicated that bromo substituted compounds

have significant protection against

pentylenetetrazole induced convulsions

which can be regarded as strong candidates

for future anticonvulsant research.

O OH

R1

+NH2

NH NH2

S

POCl3

30min,Reflux

S

N N

NH2R

1

Mohammad Shahar Yar [21] et al synthesized

a series of five membered heterocyclic

compounds by the reaction between isoniazid

and various substituted isothiocyanates and

was tested for their anticonvulsant activity by

determining their ability to provide

protection against convulsions induced by

electro convulsometer comparing with

standard drug phenytoin sodium. Among the

synthesized compounds, 2-(4-chlorophenyl)

amino-5-(4-pyridyl)-1,3,4-thiadiazole and 2-

(4-chlorophenyl)amino-5-(4-pyridyl)-1, 3, 4-

oxadiazole were found promising compounds

of the series.

Joseph et al 341


N

NH

NH2

O

NCS

R

N

NH

NH

O

S

NH

R

Conc, H2SO4

S

N N

NH

RN

A Rahman [22] et al synthesized various

substituted amine derivatives, piperidine,

aniline, and 2-amino-oxazole derivatives of

thiadiazole and characterized by spectral

data. The anticonvulsant activity of the drug

was screened using MES (Maximium

Electrshock Seizure) model using standard

drugs phenytoin and carbamazepine. Most of

these compounds showed promising

anticonvulsant activity.

Synthesis of intermediate:

N N

S SHNH2

NH2NH2 N N

S NHNH2

NH2

CH3 CH3

O O

N N

SNH2 N

N

CH3

CH3

O

Cl

Cl

N N

SNH

NN

CH3

CH3

O

Cl

From this intermediate various amine

substituted derivatives like piperidine, aniline,

2-amino –oxazole derivatives are synthesized

by reacting with corresponding amine.

Structures of thus synthesized compounds are

as follows:

Joseph et al 342


N N

SNH

NN

CH3

ON

CH3

CH3

30 amine substituted thiadiazole derivative

NN

S

NH

NN

CH3

CH3

O

NH

aniline substituted thiadiazole derivative

NN

S

NH

NN

CH3

CH3

ONH

O

N

benzoxazole substituted thiadiazole derivative

N N

SNH

NN

CH3

CH3

ON

piperidine substituted thiadiazole derivative

Anti tubercular activity

Karigar Asif A [23] et al synthesized a series of

thiadiazole derivatives using equimolar

mixture of aromatic aldehydes thioglycolic

acid and thiosemicarbazide in H2SO4. The

structures of all the synthesized compounds

were confirmed by FTIR.

NMR and Mass spectral data and their

antitubercular activity studied against

Mycobacterium tuberculosis using microplate

alamar blue assay (MABA). All the synthesized

compounds showed good anti tubercular

activity.

Joseph et al 343


CONCLUSION

Thiadiazole are important class f heterocyclic

compounds. Among the different isomers of

thiadiazole 1,3,4- thiadiazole is most studied

compound because of its various

pharmacological activities such as anticancer,

antitubercular, antimicrobial, antidiabetic,

antiinflammatory, anticonvulsant, antioxidant

activities. This review gives an overview of the

wide spectrum of pharmacological activities

exhibited by thiadiazole derivatives. The

importance of thiadiazole moiety can be

magnified by carrying out further studies on its

possible substitution and thus to synthesize

better agents that can have strong future

commitments.

CONFLICT OF INTEREST STATEMENT

The authors declare that they have no

competing interests.

REFERENCES

1. Storr RC, Gilchrist TL. Science of synthesis

Houben-Weyl Methods of molecular

transformations: Hetarenes and Related

Ring systems, five membered Herarenes

with three or more heteroatoms. Germany:

Thieme; 2003.

2. Mehta D, Taya P, Neethu. A review on

various biological activities of thiadiazole.

Int J Pharmacy Pharm Sci 2015; 7(4): 39-47.

3. Yang SJ, Lee SH, Kwak HJ, Gong YD.

Regioselective synthesis of 20 amino

substituted 1, 3, 4-oxadiazole and 1, 3, 4 –

thiadiazole derivatives via Reagent-based

cyclization of thiosemicarbazide

intermediate. J Organic Chem 2013; 78:

438-444.

4. Hu Y, Li YC, Wang XM, Yang YH, Zhu HL. 1, 3,

4- Thiadiazoles, Synthesis Reactions and

Applications in Medical, Agricultural and

Material Chemistry. Chem Rev 2014; 1-40.

RCHO + HSCH2COOH

H2SO4

OH

R S

OH

O

-H2O

NH2NHCSNH2

NH

R S

OH

O

NH

SH NH2

-H2OS

N

R

NH NH2

S

O

SN

R

N NH2

SH

OH

-H2O

S N N

SNH2

R

Joseph et al 344


5. Raj MM, Patel HV, Raj LM, Patel NK.

Synthesis and biological evaluation of some

new 1, 3, 4- thiadiazole derivatives for their

antimicrobial activities. Int J Pharm Chem

Biol Sci 2013; 3(3):814-820.

6. Kumar A, Amir M, Ali I, Khan SA. Synthesis

of Pharmaceutically important 1, 3, 4-

thiadiazole and imidazolinone derivatives as

antimicrobials. Indian J Chem 2009; 4813:

1288-1293.

7. Zong G, Zhao H, Jiang R, Zhang J, Liang X,

Baoju Li, Shi Y, Wang D. Design synthesis

and bioactivity of novel glycosyl thiadiazole

derivatives. Molecules 2014; 19: 7832-7849.

8. Gomha SM. Synthesis under microwave

irradiation of [1,2,4] triazolo [3,4-b][1,3,4]

thiadiazoles and other diazoles bearing

indole moieties and their antimicrobial

evaluation. Molecules 2011; 16: 8244-8256.

9. Asif M, Asthana C. 2,4Disubstituted -5-

imino-1,3,4-thiadiazole derivatives:

synthesis and characterization and

evaluation of anti-inflammatory activities.

Int J Chem Tech Res 2009; 1(4): 1200-1205.

10. Guptha SK, Sharma PK. Synthesis and anti-

inflammatory activity of disubstituted 1,3,4-

thiadiazole. Int J Drug Formulation Res

2011; 2(2): 344-350.

11. Panday A, Dewangan D, Verma S, Mishra A,

Dubey RD. Synthesis of Schiff base of

2.amino-5-aryl-1,3,4-thiadiazole and its

analgesic, antiinflammatory, antibacterial

and antitubercular activity. Int J Chem Tech

Res 2011; 3(1): 178-184.

12. Verma AK, Martin A. Synthesis charact-

erization and antiinflammatory activity of

analogues of 1, 3, 4 – thiadiazole. Int J of

Pharm Arch 2014; 3(9): 1-5.

13. Naskar A, Singha T, Guria T, Singh J, Kumar

AB, Maity TK. Synthesis, characterization

and evaluation of anticancer activity of

some new schiff bases of 1, 3, 4-thiadiazole

derivatives. Int J Pharmacy Pharm Sci 2015;

7(3): 397-402.

14. Banerjee S, Swaroop TVSS, Ferdy IC, Singh

A, lakshmi SM, Dr. Mohan, Dr. Saravunan J.

Indo Am J Pharm Res 2014; 2(2): 1074-

1082.

15. Rahman DEA, Moham KO. Synthesis of

novel 1,3,4- thiadiazole analogues with

expected anticancer activity. Der Pharma

Chemica 2014; 6(1): 323-335.

16. Datar PA, Deokule TA. Design and synthesis

of thiadiazole derivatives as antidiabetic

agents. Med Chem 2014; 4(4): 390-399.

17. Pattan SR, Kittur BS, Sastry BS, Jadav SG,

Thakum DK, Madamwar SA, Shinde HV.

Synthesis and evaluation of some novel 1,

3, 4 – thiadiazole for anti diabetic activity.

Indian J Chem 2011; 50(B): 615-618.

18. Harika MS, Nagasudha B, Raghavendra HG.

Synergistic activity of thiadiazole and

thiadiazolidinone derivatives against alloxan

induced diabetes in rats. Scholars Academ J

Pharm 2014; 3(3): 301-305.

19. Chitale SK, Ramesh B, Bhalgat CM, Jaishree

V, Puttaraj C, Bharathi DR. Synthesis and

antioxidant screening of some novel 1, 3, 4-

thiadiazole derivatives. Research J Pharm

Technol 2011; 4(10): 1540-1544.

20. Soni BK, Singh T, Bhalgat CM, Kamlesh B,

Kumar SM, Pavani M. In vitro antioxidant

studies of some 1, 3, 4 – thiadiazole

derivatives. Int J Res Pharm Biomed Sci

2011; 2: 1590-1592.

21. Masi HH, Gajjor AK, Savjani JK, Masi Inayal.

Synthesis and anticonvulsant activity of

novel 2,5-disubstituted 1, 3, 4- thiadiazole

derivatives. Int J Pharmtech Res 2011; 3(4):

2017-2024.

22. Shahar Yar M, Akhter MW. Synthesis and

anticonvulsant activity of substituted

oxadiazole and thiadiazole derivatives. Acta

Poloniae Pharmaceutica Drug Res 2009;

66(4): 393-397.

23. Rahman A, Shakya AK, Wahab S, Ansari NH.

Synthesis of some new thiadiazole

derivatives and their anticonvulsant

Joseph et al 345


activity. Bulgarian Chem Commun 2014;

46(4): 750-756.

24. Karigar AA, Himaja M, Male SV, Prathap KJ,

Sikarwar MS. One pot synthesis and

antitubercular activity of 2-amino -5-aryl -

5H thiazolo [4,3-b]-1, 3, 4- thiadiazoles. Int

Res J Pharm 2011; 2(1): 153-158.

Cite this article as: Lincy Joseph, Mathew George, Prabha Mathews. A Review on Various Biological Activities

of 1,3,4- Thiadiazole Derivatives . J Pharm Chem Biol Sci 2015; 3(3):329-345

a review on various biological activities of 1,3,4 ... · nh 2 (3) in the present ... of the...

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