Synthesis, Characterization and Antibacterial Activity of Bis Thiourea Derivatives

JAYAKUMAR S/O PONNIASALAN (36328)

Bachelor of Science with Honours

(Chemistry Resource)

2015

Faculty of Resource Science and Technology

SYNTHESIS, CHARACTERIZATION AND ANTIBACTERIAL

ACTIVITY OF BIS THIOUREA DERIVATIVES

JAYAKUMAR S/O PONNIASALAN

(36328)

This project is submitted in partial fulfilment of

the requirement for the degree of bachelor of science with Honours

(Resource Chemistry)

Faculty of Resource Science and Technology

University Malaysia Sarawak

2015

ACKNOWLEDGEMENT

Hereby, I would express my deepest gratitude to my supervisor, Assoc. Prof. Dr. Zainab

Ngaini for her guidance, motivation and reccomendation in completion of this thesis. Besides

that, i would like to convey my heatfelt thanks to Madam Maya Asyikin Mohd. Arif as my

co-supervisor. Furthermore, a special thanks to Postgrad student under Dr. Zainab who guide

me throughout this research. I also appreciate and acknowledge our Faculty of Resource and

Technology, Unimas for providing all the facilities for me to conduct this research. I also

thankful to lab assistant of FTIR and NMR who willing guide me to extract result from my

lab work. My special thanks also extend to my parents as well as my friends.

DECLARATION

I hereby declare that no portion of this dissertation has been submitted in support of an

application for another degree of qualification of this or any other university or institution of

higher learning.

…………………………………………

( Jayakumar A/l Ponniasalan )

Resource Chemistry Programe

Department of Resource Science and Technology

University Malaysia Sarawak

TABLE OF CONTENT

Page

List of Abbreviation…………………………………………………………………………....I

List of Figure…………………….…………………………………………………………..…II-III

List of Table………………………………..………….………………………………….…....IV

List of Scheme……………………………………………..………………………………..….IV

Abstract…………………………………………………………………………………….......1

Chapter 1: Introduction …………………………………...……..……………………….……2-3

1.1 : Problem Statement………………………………………………………………..4

1.2 : Objective……………………………………………………………………........4-5

Chapter 2 : Literature Review…………………………………...……………………………...6

2.1 Thiourea……………………………...………………………………………….….6

2.2 Synthesis Thiourea Derivative…………………...…………………………….......7

2.3 Biological Activities…………………….………………………………………...10

2.3.1 Antibacterial activities……………..………………………………….…10

2.3.2 Antiviral Activities………………………………………………….......11

2.3.3 Antifungal …………………………...…………………………….......12-13

2.3.4 Anticancer…………………………...…………………………………..14-15

2.4 The role of substituted groups and positional of substituent group.……………...16

Chapter 3: Materials and methods…………………………………………………….………..19

3.1Materials…………………………………………………………………………....19

3.2 Measurement……………………………………………………………………….19

3.3 Methodology……………………………………………………………………….20

3.3.1 Synthesis of N1,N4-bis(phenylcarbomothioyl)-2-methoxybenzamide

(27)........................................................................................................20

3.3.2 Synthesis of N1,N4-bis(phenylcarbomothioyl)-3-methoxybenzamide

(28)........................................................................................................21

3.3.3 Synthesis of N1,N4-bis(phenylcarbomothioyl)-3-methoxybenzamide

(29)........................................................................................................22

3.3.4 Synthesis of N1,N3-bis(phenylcarbomothioyl)-2-methoxybenzamide

(30)........................................................................................................23

3.3.5 Synthesis of N1,N3-bis(phenylcarbomothioyl)-3-methoxybenzamide

(31)........................................................................................................24

3.3.6 Synthesis of N1,N3-bis(phenylcarbomothioyl)-4-methoxybenzamide

(32)........................................................................................................25

3.4 Antibacterial Screening………………………………………………………………....26

3.4.1 Bacteria Culture…………………………………………………………..….26

3.4.2 Disc diffusion method…………………………………………………..…...26

3.4.3 Minimum Inhibition concentration determination……………………….....26

Chapter 4 : Results and Discussion…………………………………………………………...…….27

4.1 Synthesis of N1,N4-bis(phenylcarbomothioyl)-2-methoxybenzamide (27)…………...27-

30

4.2 Synthesis of N1,N4-bis(phenylcarbomothioyl)-3-methoxybenzamide (28)………...31-34

4.3 Synthesis of N1,N4-bis(phenylcarbomothioyl)-4-methoxybenzamide (29)………...35-38

4.4 Synthesis of N1,N3-bis(phenylcarbomothioyl)-2-methoxybenzamide (30)………..39-42

4.5 Synthesis of N1,N3-bis(phenylcarbomothioyl)-3-methoxybenzamide (31)…………...43-

46

4.6 Synthesis of N1,N3-bis(phenylcarbomothioyl)-4-methoxybenzamide (32)………...47-50

4.7 Antibacterial activities………………………………………………………….……..51-53

Chapter 5 : Conclusion and Recommendations………………………………………………….…..54

Chapter 6 : References……………………………………………………………………….…55-57

List of Abbreviations

FTIR Fourier Transform infrared spectroscopy

1H NMR Hydrogen Nuclear Magenetic Resonances

13C NMR Carbon Nuclear Magnetic Resonances

Ppm part per million

MIC Minimal Inhibitory Concentration

I

List of Figures

Figure 1 : Thiourea ..................................................................................................................................2

Figure 2 : N-(2-methoxybenzoyl)-N’-(4-diphenylamine)thiourea .........................................................3

Figure 3 : N-(2-methoxybenzoyl)-N’-(4-diphenylamine)thiourea 12...................................................11

Figure 4 : Structure of 1-[4-[(4-allyl-5-methylene-1,24-triazolidin-3-yl)methoxy]phenyl]-3-phenyl-

thiourea 13..............................................................................................................................................11

Figure 5 : 2-{[(diethyl-thiocarbamoylimino)-phenyl-methyl]-amino}-benzoic acid methyl ester 15...13

Figure 6 : 3-benzoyl-1-butyl-1-methyl-thiourea 16...............................................................................13

Figure 7 : 1-(2-,5-Dimethylphenyl)-3-phenylthiourea 19......................................................................14

Figure 8: Compound 21 and 22 ) 1-aroyl-3-aryl thiourea......................................................................16

Figure 9: 1,-(3-chlorophenyl)-3-(2-methoxy-6-pentadecylbenyl)-3-phenylthiourea 24.......................17

Figure 10: , 1-(2-methoxy-6-pentadecylbenyl)-3-phenylthiourea 23....................................................17

Figure 11: Compound 25 and Compound 26.........................................................................................18

Figure 12 : IR spectrum of N1, N4 – bis(phenylcarbamothioyl)-2-methoxybenzamide.......................28

Figure 13: 1H NMR of N1, N4 – bis(phenylcarbamothioyl)-2-methoxybenzamide.............................29

Figure 14: 13C NMR of N1, N4 – bis(phenylcarbamothioyl)-2-methoxybenzamide...........................30

Figure 15: IR spectrum of N1, N4 – bis(phenylcarbamothioyl)-3-methoxybenzamide........................32

Figure 16: 1H NMR of N1, N4 – bis(phenylcarbamothioyl)-3-methoxybenzamide.............................33

Figure 17: 13C NMR of N1, N4 – bis(phenylcarbamothioyl)-3-methoxybenzamide...........................34

Figure 18 : IR spectrum N1, N4 – bis(phenylcarbamothioyl)-4-methoxybenzamide...........................36

Figure 19: 1H NMR of N1, N4 – bis(phenylcarbamothioyl)-4-methoxybenzamide.............................37

Figure 20 : 13C NMR of of N1, N4 – bis(phenylcarbamothioyl)-4-methoxybenzamide......................38

Figure 21: IR spectrum of N1, N3 – bis(phenylcarbamothioyl)-2-methoxybenzamide........................40

Figure 22: 1H NMR of N1, N3 – bis(phenylcarbamothioyl)-2-methoxybenzamide.............................41

Figure 23: 13C NMR of N1, N3 – bis(phenylcarbamothioyl)-2-methoxybenzamide...........................42

II

Figure 24 : IR spectrum of N1, N3 – bis(phenylcarbamothioyl)-3-methoxybenzamide.......................44

Figure 25: 1H NMR of N1, N3 – bis(phenylcarbamothioyl)-3-methoxybenzamide.............................45

Figure 26: 13C NMR of N1, N3 – bis(phenylcarbamothioyl)-3-methoxybenzamide...........................46

Figure 27: IR spectrum of N1, N3 – bis(phenylcarbamothioyl)-4-methoxybenzamide........................48

Figure 28: 1H NMR of N1, N3 – bis(phenylcarbamothioyl)-4-methoxybenzamide.............................49

Figure 29 : 13C NMR of N1, N3 – bis(phenylcarbamothioyl)-4-methoxybenzamide..........................50

Figure 30: N1,N4 bis thiourea................................................................................................................54

Figure 31 : N1,N3 bis thiourea...............................................................................................................54

III

List of Table

Table 1 : Synthesized 1-aroyl-3-aryl thiourea derivatives…………………………………16

Table 2 : Zone of Inhibition in mm…………………………………………………….….17

Table 3 : Zone of inhibition in mm for concentration (µg/mL)…………………………..18

Table 4 : : Inhibitory activity and its zone of inhibition of titled thiourea derivatives........52

List of Scheme

Scheme 1 : Reaction pathway of synthesis N1,N4-bis thiourea derivatives............................................4

Scheme 2 : Reaction pathway of synthesis N1,N3-bis thiourea derivatives............................................5

Scheme 3 : Pathway of synthesis of acyl thiourea derivatives 2.............................................................7

Scheme 4 : Mechanism to synthesis thiourea 4......................................................................................7

Scheme 5 : Synthesis of thiourea from aromatic amines 6......................................................................8

Scheme 6 : Reaction pathway of synthesis acylthiourea 7.....................................................................8

Scheme 7 : Reaction pathway of 1,2-Bis[N’-(2-methoxybenzoyl)thioureido]-4-nitrobenze 8...............9

Scheme 8 : Reaction pathway of N-(2-methoxy(benzoyl)-N’-4(4-diphenylalamine)thiourea 9.............9

Scheme 9 : reaction pathway of synthesis α-benzoyl-β-phenylthiourea 10...........................................10

Scheme 10 : Reaction pathway of 1-aroyl-3-aryl thiourea 11.............................................................10

Scheme 11 : Synthesis of thiourea derivative 14...................................................................................12

Scheme 12 : Reaction pathway 1,2-Bis[N’-(2-methoxybenzoyl)thioureido]-4-nitrobenze 20..............15

Scheme 13: Synthesis of compound 27.................................................................................................27

Scheme 14: Synthesis of compound 28.................................................................................................31

Scheme 15 : Synthesis of compound 29................................................................................................35

Scheme 16: Synthesis of compound 30.................................................................................................39

Scheme 17: Synthesis of compound 31.................................................................................................43

Scheme 18: Synthesis of compound 32.................................................................................................47

IV

Synthesis, Characterization and Antibacterial Activity of BisThiourea Derivatives

Jayakumar S/O Ponniasalan

Resource Chemistry

Faculty of Resource Science and Technology

Universiti Malaysia Sarawak

Abstract

A series of bisthiourea derivatives were succesfully synthesized by reaction of benzene-1, 4-

dicarbonyl isothiocyanate intermediates and isophthaloyl dichloride, with a series of aromatic

amine at ortho, meta and para position. The structure of synthesised compound characterized

by infra-red spectroscopy (FTIR), 1H Nuclear magnetic resonances, and 13C Nuclear

magnetic resonances. The synthesised compounds were screened for their antibacterial

properties using Gram-negative bacteria Escherichia coli (E.coli) by using disc diffusion

method. All of synthesized series showed negative results towards antibacterial activity.

Keywords: thiourea, E.coli, Antibacterial activity, Amine, Spectroscopy

ABSTRAK

Satu siri bis(tiourea) derivative telah berjaya dihasilkan melalui tindakbalas antara sebatian

pertengahan benzene-1,4-dicarbonil isothiosianat, dengan terbitan amina aromatic pada

orto, meta dan para. Struktur sebatian disentesis dicirikan menggunakan spektroskopi infra

merah (FTIR), resonasmagnetiknuklear(13C NMR dan1H NMR). Sebatian disintesis telah

disaring untuk aktiviti anti-bakteria mereka menggunakan bacteria negatif Gram (E.coli)

meggunakan kaedah Cakera penyebaran. Kesemua sebatian disintesis tidak menunjukkan

perencatanlan gsung terhadap aktiviti anti-bakteria.

Kata Kunci: tiourea, E.coli, aktiviti anti-bakteria, Amina, Spektroskopi

Chapter 1

Introduction

1.1 Thiourea.

Thiourea is an organosulfur compound with chemical formula of CSN2H4 (Madan et al.,

1991).The major element in thiourea was sulphur, nitrogen and carbon. The basic structure of

thiourea is shown in Figure 1 below. The melting point and molar mass of thiourea are 182 ◦C

and 76.12 g/mol respectively. Thiourea is white crystalline form which very soluble in polar

solvent likes water and insoluble in non-polar solvent (Claude et al., 2013). Thiourea and

urea are structurally similar except oxygen atom in urea have been replaced by sulfur atom,

thus it contribute to the differences in properties (Loto et al, 2012).

H2N

C

NH2

S

Figure 1 :Thiourea

Thiourea was actively used in organic synthesis due to it versatile reagent properties which

able to make coordination bond with metal centres as neutral ligand, monoanions or dianions.

These bonding possibilities are due to the oxygen, nitrogen and sulphur donor atom of

thiourea derivatives (Yahyazadeh et al., 2013).The mechanism in synthesizing thiourea is

nucleophilic attack at the electrophilic carbon of thiocyanate ion by amine (McEwen, 1991).

Besides, thiourea derivative are capable in wide range of biological activities such as

antibacterial, antiviral, anticancer, anticonvulsion, analgesic and HDL-elevating properties

(Yahyazadeh et al., 2013). Moreover, thiourea was also reported was used in controlling

plant pathogen (Fernandez et al., 2005).

In a study done by Mohamad Halim (2011), monothiourea compound N-(2-

methoxybenzoyl)-N’-(4-diphenylamine)thiourea (1) showed good antibacterial properties

against Staphylococcus aureus with 9.5 mm zone of inhibition. Acyl thiourea exhibit superior

pesticides, fungicidal, antiviral and involve in plant grow activity (Saeed et al., 2009).

(1)

Figure 2: N-(2-methoxybenzoyl)-N’-(4-diphenylamine)thiourea1

O

NHNH

N

H

1.1 Problem Statement

Many researchers have been reported on the synthesis of mono-thiourea. Due to the fact,

mono thiourea exhibit good antibacterial properties (Saeed et al., 2009). Bisthiourea is now

widely explore to study the effectiveness of its antibacterial properties. Therefore in this,

research bisthiourea derivative bearing amine at O, P and M position were synthesised and

tested for antibacterial properties against E.coli.

1.2 Objective

1. To synthesis new bis(thiourea) derivatives bearing aromatic substituted alkyl groups

at Ortho, Meta and Para position as shown in scheme 1 and 2.

Scheme 1: Reaction pathway of synthesis N1,N4-bis thiourea derivatives

R

R

R

R- OCH3

KSCN

ACETONITRILE

C

C

Scheme 2: Reaction pathway of synthesis N1,N3-bis thiourea derivatives

2. To characterize bisthiourea derivatives using FTIR, 1H NMR and 13C NMR,

3. To study the antibacterial properties of the synthesized bisthiourea derivatives against

Escherichia coli.

R

R

R

R- OCH3

KSCN

ACETONITRILE

C

C

Chapter 2

Literature Review

2.1 Thiourea

Thiourea derivatives is versatile ligand and able to coordinate as neutral ligand, monoanions

or dianions to metal centres (Arslan, 2009). The oxygen, nitrogen and sulphur act as donor

atom thus providing wide range multitude of bonding possibilities (Arslan,2009). Thiourea

derivative coordinate to some transition metal ion to form stable complexes

(Alkherraz,2014). Thiourea was used in the reductive work-up of ozonolysis to produce

carbonyl compound because of thiourea is odourless and non-volatile due to its polarity

(Alkan,2011).

Thiourea is very effective in control plant pathogen (Fernandez,2005). Acyl thiourea also was

used in fungicidal, antiviral and regulation activities for plant growth in planting industry.

According to, Zhong et al, (2008) undergoes research on synthesis of acyl thiourea

derivatives of chitosan (CS) and their properties with bacterial. They obtained a clear agar

when tested with bacteria such as Echerichia coli, Pseudomonas aeruginosa, Staphylococcus

aures and Sarcina.The test proved that this compound produce a clear agar, which can be

conclude that this compound does exhibit antibacterial properties. The pathway of synthesis

of acyl thiourea derivatives illustrated in scheme (3) below.

H

C

R

H

R

H

(2)

Scheme 3 : Pathway of synthesis of acyl thiourea derivatives2

2.2 Synthesis of thiourea derivative

Thiourea derivative (5) 7-chloroquinolinyl thioureas usually synthesis by the action of

nucleophilic amine (4) reactivity toward electrophilic carbon of thiocyanate ion (3) (Mahajan

et al., 2007). The general mechanism is shown in Scheme 4.

NCl

N

+ R-NH2

CS

NCl

HN NH

S

R

(3) (4) (5)

Scheme 4: Mechanism to synthesis thiourea4

One of the example synthesis of unsymmetrical thiourea derivatives as shown in Scheme 5.

1-Ethyl-3-(3-hydroxyphenyl)thiourea (6) was successfully synthesised by the reaction of

aromatic amine with ethylisothiocyanate in acetone. Aromatic amine was used to produce

67% of yield of compound after purification (Yahyazadeh et al., 2013).

(6)

Scheme 5: Synthesis of thiourea from aromatic amines 6

Thiourea was also reported as N,N-disubstituted thiourea and N-acylthiourea. Acyl thiourea

was widely used in numerous transformations. For example acylthiourea were used to

synthesise of four-, five-,six-,and seven- membered heterocyclic ring system. The compound

was studied for good antibacterial, antiarthrictic and anticoagulant agent. According to Alan

et al., (2004) acylthiourea was believed to increase antifungal activities in plant. Pathogen

that causes infection and alteration of development stages of plant can be inhibited. These

infected plants have high tendency to cause serious health problem to consumers (Paola et al.,

2011). For example acylthiourea (7) was synthesised by the reaction of

aminothiocarbonylimitoyl chlorides with potassium thiocyanate (Alan et al., 2004). The

reaction pathway is shown in Scheme 6.

N HN R3 N NH

R3

O

R1

R2

KCNS

H2O

R1

R2

S ClS

(7)

Scheme 6 : Reaction pathway of synthesis acylthiourea7

Other than that, 1,2-Bis[N’-(2-methoxybenzoyl)thioureido]-4-nitrobenze (8) was synthesised

from the reaction of benzoyl isothiocyante with 4-chloro-1,2-phenylenediamine as shown in

Scheme 7. This reaction produced 69% yield. This compound contain two thiourea moieties

R

NH2

+ Et-N=C=Sacetone

r.tr.t / 15 hR

NH NH

Et

S

that contribute to good antibacterial activities against Staphylococcus aueus.Moreover, the

this compound exhibit good antibacterial properties due to that it contain three penyl group

and an halogen atom (Shaikhet al., 2014).

NH

O

O

N

S

Cl

N

N

S

O

O

O

N C S

0

Cl

Cl NH2

NH2NH4SCN

acetone acetone

(8)

Scheme 7: Reaction pathway of 1,2-Bis[N’-(2-methoxybenzoyl)thioureido]-4-nitrobenze 8

Venkatesh (2009) synthesised heterocyclic based thiourea derivatives. 1-pyridin-2yl-thiourea

(9) was synthesised reaction of 2-aminopyridine on to ammonium thiocyanate in methanol

with the yield ranging from 64-85 %. Compound 8 exhibit good anti-oxidant with 76.7%

inhibition on lipid peroxide level. The reaction pathway was shown in scheme 8.

(9)

Scheme 8 : Reaction pathway of N-(2-methoxy(benzoyl)-N’-4(4-diphenylalamine)thiourea 9

Frank et al., (1995) reported on α-benzoyl-β-phenylthiourea 10 when synthesised by the

reaction of ammonium thiocyanate and benzoyl chloride. Aniline that act as amine was added

and yellow precipitate compound 10 formed with 85% of yield as shown in Scheme 9.

N NH2

+

NCS

HClN

CNH

S

NH4SCNPhCOCl

N=C=S

O

Ph

PhNH2

Ph NH

NH

Ph

O S

(10)

Scheme 9 : reaction pathway of synthesis α-benzoyl-β-phenylthiourea 10

2.3 Biological Activities of Thiourea Derivatives

2.3.1 Antibacterial activities

Saeedet al (2009) reported, 1-aroyl-3-aryl thiourea (11) showed antibacterial properties

against Escherichia coli and Staphylococcus aureus.1-aroyl-3-aryl thiourea (11) was

synthesised by the reaction of aryl chlorides and potassium thiocyanate with addition of

substituted anilines. The substituent like halo groups result in effectiveness in antibacterial

properties (Saeed et al., 2009). The reaction pathway is shown in Scheme 10.

(11)

Scheme 10: Reaction pathway of 1-aroyl-3-aryl thiourea 11

OHO

R1

SOCL2

N S-K+

O NC

S

R1

R2NH2

dry acetone NH

NH

OS

R2R1

In 2011, Halimet al., synthesised N-(2-methoxybenzoyl)-N’-(4-diphenylamine)thiourea (12)

and the compound was reported to show antibacterial properties against Staphylococcus

aureus with 9.5mm zone of inhibition. The Antibacterial activity of the thiourea was

believed to enhance with the metal such as copper.

O

O

NH

S

NH

N

H

(12)

Figure 3 :N-(2-methoxybenzoyl)-N’-(4-diphenylamine)thiourea12

2.3.2 Antiviral Activities

According to Chen (2010) the substitution place, electronic, steric effect and linker length

greatly affect the antiviral activities. Compound 1-[4-[(4-allyl-5-methylene-1,24-triazolidin-

3-yl)methoxy]phenyl]-3-phenyl-thiourea (13) reported to exhibit antiviral characteristic

against Coxsackie virus B4 due to the ally group at the N-4 of the 1,2,4-triazole ring and

phenyl moiety at the terminal nitrogen (Kucukguzel et al.,2008).

(13)

Figure 4 : Structure of 1-[4-[(4-allyl-5-methylene-1,24-triazolidin-3-yl)methoxy]phenyl]

Phenyl-thiourea 13

NH

NH

O

N

N

N

H

S

S

The reaction of 5-[(4-aminophenoxy) methyl]-4-alkyl/aryl-2,4-dihydro-3H-1,2,4-triazole-3-

thiones with amines group that contain alkyl or aryl isothiocyanates in the dry acetone as

solvent successfully obtained 1-alkyl/aryl-3-{4-[(4-alkyl/aryl-5-thioxo-4,5-dihydro-1H-1,2,4-

triazol-3-yl)-methoxy]-phenyl}thiourea derivatives (14). This compound has an ally group at

the N-4 of the 1, 2,4-triazole ring and phenyl moiety at the terminal nitrogen is active

derivative against viral. This compound show antiviral properties against Coxsackie virus

B4.Scheme 11 shows the synthesis of compound (14).

R1

R2-NCS

ACETONE,REFLUX R2R2

R1 = CH3 ; C2H5 ; CH2CH=CH2 ; C6H5

R2 = CH3 ; C2H5 ; CH2CH=CH2 ; C6H5

(14)

Scheme 11: Synthesis of thiourea derivative 14

2.3.3 Antifungal Activities

Synthesis of thiourea derivatives of methyl anthranilate as 2-{[(diethyl-thiocarbamoylimino)-

phenyl-methyl]-amino}-benzoic acid methyl ester 15 was reported to exhibit antifungal

properties and inhibit growth of plant pathogen that induce plant diseases such as

Phomabetae and Fusariumoxysporum ( Campo et al., 2004).

N

COOCH3

N

N

S

R1 R2

H

(15)

Figure 5 :2-{[(diethyl-thiocarbamoylimino)-phenyl-methyl]-amino}-benzoic acid methyl

ester 15

Del Campo (2004), also reported 3-benzoyl-1-butyl-1-methyl-thiourea (16) showed

antifungal activity and suppresses the growth of Penicilliumdigitatum and Saccharomyces

cerevisiae.

(16)

Figure 6: 3-benzoyl-1-butyl-1-methyl-thiourea 16

O

HN

S

N

CH3

2.3.4 Anticancer

Cancer was reported as world major health problem. Early tumour detection increased the

survival rate of cancer patients. Phenyl thiourea derivatives was reported to be use to prevent

and treat cancer by inhibit the telomerase activity. 1-(2-, 5-Dimethylphenyl)-3-phenylthiourea

(19) was synthesised by using phenyl isothiocyanate added with substituted aromatic and fat

amine (Guaet al., 2014).

HN NH

(19)

Figure 7 : 1-(2-,5-Dimethylphenyl)-3-phenylthiourea 19

Other than that, bisthiourea compound (20) 1-(2, 2-diphenylethyl)-3-[3-{7-[3-(2,2-

diphenylethylcarbamo thioylamino)propylamino]heptylamino}propyl]thiourea. Compound

(20) was prepared from the reaction of N,N’-bis(3-aminopropyl)heptane-1,7-diamine and

[isothiocyanato(phenyl)methyl]benzene (20) was also reported to initiate methylation at

histone 3 lysine 4 chromatin mark and specific target of lysine-specific demethylase in lung

carcinoma cell. Lysine-specific demethylase responsible and control development of cancer

(Sharma et al., 2010).