it it

it it

is is

by by

or~ or~

up up

are are

An­

the the

ox­

Al­

ve ve

113 113

kan­

tox­

büyük büyük

fndal, fndal,

is is

to to

that that

and and

be be

hidrojen hidrojen

macro­

en en

oxygen­

since since

they they

çalışmalar çalışmalar

bileşiklerin bileşiklerin

ve ve

olarak olarak

almaktadır. almaktadır.

olduğu olduğu

hastalıklann hastalıklann to to

can can

benzinıidazol benzinıidazol

with with

which which

it it

radikal, radikal,

Antioksidan Antioksidan

kimyasallar kimyasallar

ve ve

explained explained

yer yer

radical radical

electron electron

türevi türevi

importantly, importantly,

orbit, orbit,

neden neden

dismutase. dismutase.

radicals radicals

sahip sahip

be be

anyonu anyonu

önemli önemli

bulunmaktadır. bulunmaktadır.

harmful harmful

gösteren gösteren

fndol fndol

is is

Serbest Serbest

radical radical

organiwıanın organiwıanın

gibi gibi

anion anion

radical, radical,

their their

çevresel çevresel

more more

single single can can

converted converted

rolü rolü

gelişmeler gelişmeler

a a

düşmeye düşmeye

based based

is is

in in

Bileşiklerin Bileşiklerin

hidroksil hidroksil

particularly particularly

1). 1).

free free

aktiviteye aktiviteye

of of

in in

and, and,

yeni yeni

benzirnidazol benzirnidazol

kanser kanser

a a

oynadığını oynadığını

oxygen oxygen

açabilirler. açabilirler.

rağmen rağmen

Ankara Ankara

enzimler enzimler

superoxide superoxide

ve ve

ve ve

hydroxyl hydroxyl

Türevi Türevi

cells, cells, ilgili ilgili

rol rol

yol yol

Aktiviteleri Aktiviteleri

anyon, anyon,

Antioksidan, Antioksidan,

Benzinıidazol Benzinıidazol

and and

oxygen oxygen

düzeyinde düzeyinde

taken taken

itself itself

superoxide superoxide

(Figure (Figure

electron electron

radikallerin radikallerin

ile ile

mechanism mechanism

by by

Buna Buna

the the

nefrit nefrit

indol indol

: :

addition addition

antioksidan antioksidan

not not

Inspired Inspired

to to

the the

the the

önemli önemli

Tandoğan, Tandoğan,

within within

is is

This This

antioksidan antioksidan

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oxygen oxygen

of of

serbest serbest

2 2

süperoksit süperoksit

reaction reaction

hastalıklara hastalıklara

concentrations concentrations

ve ve

ü

antioksidan antioksidan

aktiviteleri aktiviteleri

Benzimidazol Benzimidazol

2

makalede makalede

unpaired unpaired

06100 06100

the the

havoc havoc

gibi gibi

kelimeler kelimeler

H

ve ve

sistemleridir. sistemleridir.

reduced reduced

reactive. reactive.

sistemde sistemde

Bu Bu

toxic toxic

of of

bileşiklerin bileşiklerin

an an

produces produces

Arterosikleroz, Arterosikleroz,

çesitli çesitli

high high

Dalı, Dalı,

radicals. radicals.

Indole Indole

be be

Fenton Fenton

ve ve

5% 5%

at at

İndol İndol

to to

though though

highly highly

vardır. vardır.

ygen ygen catalytic-reduced catalytic-reduced

tioksidanlar tioksidanlar

the the ser ser

immun immun can can

molecules3A. molecules3A.

türevi türevi

free free ic ic etiyolojisinde etiyolojisinde

ganizmanın ganizmanın

wreaks wreaks

antioksidan antioksidan koruma koruma

have have Özet: Özet: most most

Anahtar Anahtar

peroksit peroksit

of of

Anabilim Anabilim

a a

in in

to to

of of

as as

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by by

ac­

de­

this this

can can

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that that

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are are

Kimya Kimya

major major

lead lead

PÜSKÜLLÜ' PÜSKÜLLÜ'

such such

Ben-

can can

and and

radical. radical.

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Reactive Reactive problem problem

and and

and and

DNA DNA

systems systems

antioxidant antioxidant

peroxide peroxide

thus thus

There There

Herein Herein

superoxide superoxide

to to

antioxidant antioxidant

Orhan Orhan

atherosclerosis, atherosclerosis,

and and

have have

Indole, Indole,

radicals radicals

REWIEVS REWIEVS

Farmasötik Farmasötik

indole indole

activity, activity,

species species

Derivatives Derivatives

the the

M. M.

chemicals chemicals

as as

constituents constituents

Benzimidazole Benzimidazole

survive. survive.

system. system.

sources. sources.

hydroxyl hydroxyl

protective protective

of of

free free

synthetic synthetic

hydrogen hydrogen

2000 2000

also also

oxygen, oxygen,

that that

diıtioxidants diıtioxidants

damage damage

of of

to to

continuous continuous

and and

such such

derivatives. derivatives.

radical, radical,

Activities Activities

biomolecules biomolecules

and and

organism organism

and and

a a

can can

Fakültesi, Fakültesi,

reactive reactive

major major

role role

The The

immune immune

Hence, Hence,

external external

the the

is is

antioxidant antioxidant

chemical chemical

lndole lndole

SCIENTIFIC SCIENTIFIC

report report

Free Free

the the

113-119, 113-119,

singlet singlet

of of

anion anion

ALAGÖZ', ALAGÖZ',

the the

against against

cel!sl,2. cel!sl,2.

of of

diseases diseases

environmental environmental

are are

developments developments

/rom /rom

several several

in in

25, 25,

Derivatives Derivatives

are are

Oxidative Oxidative

have have

Eczacılık Eczacılık

possible possible

level level

the the

enzyrnes enzyrnes

which which peroxide peroxide

diseases. diseases.

a a

benzirnidazole benzirnidazole

species species

role role

chemically chemically

Sci., Sci.,

on on

guard guard

include include

is is

hydroxyl hydroxyl

Zeynep Zeynep

recent recent

Activities Activities

, ,

and and

systems systems

required required

0

important important

radicals radicals

zimidazole zimidazole

are are

However, However,

Antioxidant, Antioxidant,

carcinogenesis. carcinogenesis.

the the

some some

damage damage

13.07.1999 13.07.1999

25.01.2000 25.01.2000

25.01.2000 25.01.2000

studies studies

of of

various various

enzymes. enzymes.

: :

There There

must must

are are

derivatives derivatives

anion, anion,

TARAMALAR/ TARAMALAR/

Üniversitesi, Üniversitesi,

Pharnı. Pharnı.

to to

antioxidant antioxidant

: :

oxygen oxygen

impact impact

free free

and and

indole indole

species species

important important

of of

hydrogen hydrogen

J. J.

and and

enzyme enzyme

and and

and and

af af

the the

SÜZEN*

an an

radicals radicals

cells cells

reported reported

Antioxidant Antioxidant

organism. organism.

etiology etiology

Ankara Ankara Correspondence Correspondence

° °

Free Free

* *

Revised Revised

attack attack

zimidazole zimidazole

oxygen oxygen been been that that

crease crease

reactive reactive

the the

Damage Damage

number number INTRODUCTION INTRODUCTION

DNA DNA

superoxide superoxide

Because Because

compounds compounds

anion, anion,

the the cancer cancer Antioxidant Antioxidant tivities tivities

negative negative

plays plays

Keywords Keywords

Accepted Accepted

oxidant oxidant Sibel Sibel BİLİMSEL BİLİMSEL nephritis nephritis

Benzimidazole Benzimidazole

FABAD FABAD Summary Summary

a a

is is

of of

as as

its its

by by

to­

re­

ac­

de­

dif­

lip­

it it

uni­

spe­

in in

con­

they they

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high high

elec­

to to

dam­

anion anion

gener­

condi­

is is

under­

the the

in in

oxygen oxygen

The The

thereby thereby

environ­

generate generate

hydroxyl hydroxyl

is is

SAR. SAR.

due due

radical radical

limited limited

since since

because because

bond bond

derivative, derivative,

considered considered

was was

readily readily

reactive reactive

it it

which which

various various

can can

accepts accepts

peroxide. peroxide.

reactive reactive

Thus Thus

the the

readily readily

the the

it it

There There

that that

be be

singlet singlet

membrane membrane

quickly quickly

species. species.

destructive destructive

the the

and and

HzOz HzOz

have have

aqueous aqueous

superoxide superoxide

indole indole

can can

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highly highly

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species species

covalent covalent

molecule molecule

SAR SAR

where where

INDOLE INDOLE

in in

usually usually

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DNA, DNA,

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formed, formed,

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a a

2 2

documented documented

hydrogen hydrogen

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(SAR) (SAR)

not not

enzymes enzymes

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toxic toxic

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OF OF

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0

Besides Besides

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any any

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(L00°) (L00°)

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membranes membranes

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cells. cells.

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is is

Radical Radical

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Hydroxyl Hydroxyl

an an

hydroxyl hydroxyl

electron electron

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with with

human human

that, that,

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especially especially

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once once

not not

substrates substrates

mitochondria mitochondria

ACTMTY ACTMTY

in in

time time

!hat !hat

The The

formed formed

within within

cellular cellular

with with

rapidly rapidly

Anion Anion

radical radical

not not

a a

several several

single single

reactive reactive

sites sites

molecules molecules

Peroxide Peroxide

and and

is is

Rad.ical Rad.ical

opposite opposite

a a

is is

formation formation

which which

exist exist

at at

to to

Üz Üz

held held

oxidise oxidise

electrons electrons

would would

peroxyl peroxyl

reduces reduces

species. species.

of of

restriction. restriction.

reactivity reactivity

reactivity. reactivity.

its its

hydrogen hydrogen

these these

most most

biological biological

carbohydrates. carbohydrates.

reacts reacts

is is

to to

of of

agreement agreement

biological biological

Moreover, Moreover,

also also

one one

itself itself

of of

through through

spins spins

which which

and and

it it

two two

dismutation dismutation

species, species,

nuclear nuclear

2 2

but but

hydroxyl hydroxyl

spin spin

toxic toxic

and and

high high

a a

Hydrogen Hydrogen

Superoxide Superoxide

Hydroxyl Hydroxyl

molecule molecule

1. 1.

generally generally

2. 2. ceptance ceptance

this this grees grees

distribute distribute

intermediates. intermediates.

trons trons goes goes

wards wards stitutes stitutes

action action

radical radical HzOz HzOz

versal versal

<10z) <10z) The The

ated. ated.

radical, radical,

ability ability

Hz0

cies cies fuses fuses ment. ment.

have have The The

Within Within

gen gen

ages ages

tions tions concentrations concentrations

its its

3. 3.

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ids ids

as as

DERIVATIVES DERIVATIVES

ANTIOXIDANT ANTIOXIDANT

Melatonin, Melatonin,

° °

in in

to to

2

as as

by by

an an

in­

re­

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celi celi

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+OH +OH

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return return

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oxidative oxidative

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P450 P450

into into

have have

important important

mainly mainly

contain contain

discovered discovered

follows follows

free free

species, species,

human human speciesn speciesn

Üz Üz

cancerogenic cancerogenic

produced produced

Considerable Considerable

a a

intra­ normal

d.isorders d.isorders

On On

is is

oxygen-based oxygen-based

referred referred

flow flow

OH OH

are are

very very

Üz Üz

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SPECIES SPECIES

xenobiotics xenobiotics

feature feature

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radicals radicals

death death

peroxidation peroxidation

taken taken

or or

electrons electrons

are are

abnorrnal abnorrnal

energy energy

molecule molecule

molecules molecules

During During

cellular cellular

which which

each each

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degradation degradation

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causative causative

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oxygen oxygen

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celi celi

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functionsS,6. functionsS,6.

have have

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of of

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blood blood

lipid lipid

and/ and/

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+3 +3

as as

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maintain maintain

central central

e e

diseases. diseases.

Cytochrome Cytochrome

of of

reduced reduced

therefore therefore

the the

pair pair

species species

F F

of of

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a a

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inhibit inhibit

OXYGEN OXYGEN

blocking blocking

body body

areas areas

destruction. destruction.

active active

a a

some some

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metabolise metabolise

oxide oxide

oxidase. oxidase.

of of

neurological neurological

that that

suggests suggests

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neuronal neuronal

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causes causes

% %

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oxygen oxygen

substances substances

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oxygen oxygen

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brain brain

Üz Üz

known known

and and

1-4 1-4

tissue tissue

production production

partially partially

nitric nitric

products products

mutagenic mutagenic

accept accept

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implicated implicated

the the

agents agents

lipid lipid

neurodegeneration neurodegeneration

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Reaction. Reaction.

ischemialZ. ischemialZ.

species, species,

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formation formation

variety variety

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various various

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of of

evidence evidence

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levels levels

REACTIVE REACTIVE

effective effective

a a

the the

are are

the the

generated generated

Most Most

Püsküllü Püsküllü

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that that

the the

Active Active

in in

cytochrome cytochrome

have have

production production

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role role

electrons electrons

mechanisms9,!0. mechanisms9,!0.

90% 90%

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electron electron

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have have

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for for

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enzymes enzymes

göz, göz,

neurodegenerative neurodegenerative

forms forms

oxygen oxygen

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to to

estimated estimated

cerebral cerebral

the the

endogenous endogenous

stress-induced stress-induced

l. l.

decade decade

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may may

reaction7 reaction7

Ala Ala

of of

in in

four four

radicals radicals

over over

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known known

radicals radicals

radica!sl3. radica!sl3.

An An

apoptosis. apoptosis.

describing describing

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is is

would would

Free Free

membranes. membranes.

riods riods

roles roles Figure Figure

cluding cluding

implicated implicated

Süzen, Süzen, pendent pendent

chain chain

idative idative

certain certain

formerly formerly sponsible sponsible

various various

free free

114 114

els els different different

circumstantial circumstantial

it it known known stress stress Pharrnacological Pharrnacological cellular cellular

IMPORTANT IMPORTANT only only

nal nal cess, cess,

ochondrial ochondrial

Well Well is is propertiesB. propertiesB.

hand hand

ter. ter.

resulting resulting

it it unpaired unpaired

reactive reactive free free however, however,

an an

al­

in­

the the

rel­

115 115

car­

and and

!hat !hat

pre­

kid­

rad­

vas­

anti­

deg­

ester ester

of of

com­

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mem­

indol-

in in

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might might

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of of

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induced induced

receptor receptor

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new new

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derivatives derivatives

thiocyanate thiocyanate

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ability ability

growth growth

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showed showed

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of of

which which

to to

tropine tropine

oxide oxide

A A

!hat !hat

mediated mediated

and and

-

in in

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(b) (b)

by by

amine amine

the the

4 4

(Figure (Figure

responses responses

efficient efficient

degrades degrades

oxindol-3-yl oxindol-3-yl !hat !hat

2 2

radica12ı. radica12ı.

-

ferric ferric

planı planı

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Oxindol-3-carbinol Oxindol-3-carbinol acid acid

serotonin serotonin

donar. donar.

reperfusion reperfusion

in in

found found

to to

NH

presumed presumed

found found

eyde eyde of of

at at

(b) (b)

hormone hormone

contrast contrast

1 1

N N

more more

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the the

activities activities

~NH_J,O ~NH_J,O

~CHıOH ~CHıOH

is is

activity. activity.

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step step

serotonin serotonin

in in

enzymatically enzymatically

CHı CHı

was was

were were

peroxidation peroxidation

abolished abolished

by by

hydroxyl hydroxyl

~ ~ electron electron

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plant plant

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times times

5-hydroxyindole 5-hydroxyindole

pyrazinone pyrazinone

and and

5)23_ 5)23_

final final

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mitochondrial mitochondrial

-

part part

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observed observed

Comparison Comparison

lipid lipid

factor factor

doses19_ doses19_

is is

in in

NH NH

of of

100 100

peroxidase peroxidase

as as

Hyperoxides Hyperoxides

the the

study study

determinant determinant

against against

a a

bed bed

lH-indol-3-yl-methyl)-5-methoxy-3-

Antioxidant Antioxidant

is is

antioxidant antioxidant

but but

(Figure (Figure

acid acid

compound compound

was was

6-

acts acts

isolated isolated

. .

measured measured

addition, addition,

via via

tropic tropic

inhibit inhibit

occurring occurring

key key

compounds compounds

persistent persistent

higher higher

4) 4)

22

damage damage

non-enzymatically non-enzymatically

a a

oxide-pathway" oxide-pathway"

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ability ability

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[lH]-indol-3-carbonic [lH]-indol-3-carbonic

to to

in in

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aı20 aı20

ischaemia. ischaemia.

another another

acetylcholine acetylcholine

NH NH

drug drug

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as as

and and

were were

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vascular vascular

3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indol 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indol

strong strong

et et

in in

in in

(a) (a)

structure structure

4. 4.

3. 3.

peroxidation peroxidation

saff!ower. saff!ower.

(Figure (Figure

effect effect after after

"nitric "nitric

acetic acetic methanol methanol

naturally naturally

compound compound

WCH,COOH WCH,COOH

development 3-yl 3-yl Lipid Lipid

3-yl 3-yl

(2-methylpropyl)-2-(lH) (2-methylpropyl)-2-(lH) the the

brane brane

Zhang Zhang

tocopherol tocopherol

dominantly dominantly

atively atively

l,4-dimethyl-5H-pyrido[4,3-b]indol l,4-dimethyl-5H-pyrido[4,3-b]indol

pha-tocopherol pha-tocopherol

radation radation

indeno-indol indeno-indol

neys neys scavenging scavenging binol binol

lndole-3-acetic lndole-3-acetic Figure Figure

ical-induced ical-induced

method method

pounds pounds

toxic toxic

Figure Figure ofa ofa nephritic nephritic

from from function function

antagonist antagonist

forearm forearm transient transient

HCl18. HCl18.

odilatation. odilatation.

volved volved

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Melatonin Melatonin

endotoxins endotoxins

the the

carried carried

via via

glandin glandin

both both

whereas whereas the

in in

by by

amine amine

and and

oxo-iron oxo-iron

plays plays

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in in

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is is

/ /

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oxygen oxygen

2

produces produces

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Serolonin Serolonin

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is is

tissues tissues

0

nucleophile nucleophile

mechanisms mechanisms

cytoskeleton cytoskeleton

2

alsa alsa

an an scavenged scavenged

oxidative oxidative

be be

is is

neurodegenerative neurodegenerative neurons neurons

neurodegenerative neurodegenerative

2000 2000

neurodegenerative neurodegenerative

melatonin melatonin

and and

pineal pineal

effects, effects,

neurohormone neurohormone

is is

be be might

tryptamine-4,5-dione tryptamine-4,5-dione

system15. system15. It It

caused caused

the the

to to

5-hydroxytryptamine 5-hydroxytryptamine

influences influences

of of

of of

by by

implicate implicate

. .

reaction reaction

biogenic biogenic

the the

14

formation, formation,

of of

on on

other other

other other

2) 2)

xanthine xanthine

This This

unicells. unicells.

!hat !hat

immunomodulation; immunomodulation;

direct direct

and and

the the

perhaps perhaps

melatonin melatonin

113-119, 113-119,

by by

peripheral peripheral

oxygen/H

and and

Nü Nü

the the

putative putative intraneuronal

and and

and and

and and

intermediate intermediate

of of

pathological pathological

immune immune

25, 25,

damage damage

serotonin serotonin

formula formula

serotonergic serotonergic

intraneuronal intraneuronal

evidence evidence

the the

antioxidant, antioxidant,

suggested suggested

as as

neurodegeneration neurodegeneration

firstly firstly

(Figure (Figure

brain16. brain16.

processes of of

When When

prevention prevention

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of of

by by

of of

the the

by by

Oxidation Oxidation

Sci., Sci.,

to to

influences influences

various various

including including

plants plants

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possibility possibility

secreted secreted

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in in

radical radical

the the

CH2CH2NHCOCH3 CH2CH2NHCOCH3

action action

been been

such such

the the

protection, protection,

in in

in in

in in

mediated mediated

glutamate-mediated glutamate-mediated

in in

lines lines

the the

photoperiods photoperiods

in in

Chemical Chemical

has has

neuronal neuronal

The The

involves involves

4-(S-glutathionyl)-5-hydroxytryptaminel7. 4-(S-glutathionyl)-5-hydroxytryptaminel7. Phnrm. Phnrm.

tryptamine-4,5-dione tryptamine-4,5-dione

carbocation carbocation

formed formed

Melatonin Melatonin

role role

sites sites

biological biological

to to

2) 2)

2. 2.

serotonin) serotonin)

J. J.

presence presence

UNJ UNJ

anion anion

oxidations oxidations

It It

systemic systemic

new new

system system

disorders. disorders.

innervated innervated

disorders. disorders.

perhaps perhaps

contribute contribute

raises raises

hormone hormone

0~ 0~

scavenger scavenger

1

useful useful

the the

vertebrates, vertebrates,

a a

protection protection

cı-ı

that that

diated diated

rotonin rotonin

tabolites tabolites Figure Figure

tamine-4,5-dione. tamine-4,5-dione.

gions gions

brain brain and and

7-(S-glutathionyl)tryptamine-4,5-dione, 7-(S-glutathionyl)tryptamine-4,5-dione,

tathione, tathione, This This ating ating

ischemia-reperfusion, ischemia-reperfusion,

give give

(5-HT, (5-HT,

in in putative putative

ischemia-reperfusion, ischemia-reperfusion, phetamine, phetamine,

of of

of of

oxide oxide

antioxidative antioxidative underlie underlie

rotransmitters rotransmitters

ondly, ondly,

diseases. diseases.

Many Many

brain brain

tropic. tropic. antioxidant antioxidant calmodulin calmodulin

portant portant

(Figure (Figure

be be

sponse sponse

binding binding is is

ical ical portant portant FABAD FABAD

el el

of of

in in

in in

the the

are are

an­

that that

nat­

that that

this this

sen­

con­

they they

sug­

class class

were were

scav­

binds binds

inter­

or or

attack attack

Mil Mil

photo­

reason reason

or or

radica! radica!

amino­

by by

of of

guanine guanine

a a

of of

common common

this this

sites sites

of of

riboflavin riboflavin

of of

been been

by by

mannitol. mannitol.

when when

induce induce

~ ~

of of

vitae vitae

superoxide superoxide

be be

acid acid

~COOH ~COOH

.. ..

in in

irnplies irnplies

substitute substitute alone alone

the the

denaturated denaturated

NH NH

by by

guanines guanines

oxygen oxygen

for for

has has

out out

effect effect

caused caused

and and

by by

inter-molecular inter-molecular

superoxide superoxide

involvement involvement

It It

radiation radiation

pattern pattern

one one

and and

all all

not not

(b) (b)

compound compound

photoexcited photoexcited

typica! typica!

might might

the the

xanthine-xanthine xanthine-xanthine

of of

position position

superoxide superoxide

8) 8)

cleavage cleavage

benzimidazole benzimidazole

benzimidazole benzimidazole

that that

is is

Cll_ı Cll_ı

a a

positions positions

The The

damage27 damage27

but but

The The

toward toward

nm) nm)

the the

active active

of of

carried carried

reactive reactive

of of

peroxide peroxide

BITN BITN

the the

behaviour behaviour

with with

damage damage

~ ~

by by

reported reported

to to

having having

mechanism mechanism

where where

the the

CH~ CH~

CHı CHı

neither neither

are are

(b) (b)

the the

abolished abolished

2-phenylbenzimidazole-5-

by by

DNA DNA

to to

(Figure (Figure

been been

destruction. destruction.

chromatin. chromatin.

The The

extent, extent,

to to

molecules molecules

that that

suggest suggest

formation formation

2·phenyl 2·phenyl

catalase catalase

in in

been been

oxygen. oxygen.

DNA DNA

(290-320 (290-320

benzimidazole-5-sulfoniı.: benzimidazole-5-sulfoniı.:

number number

both both

acid, acid,

resctivity resctivity

DNA, DNA,

has has

and and

benzimidazole benzimidazole

Acanthocheilonema Acanthocheilonema

derivatives. derivatives.

the the

hydrogen hydrogen

and and

has has

these these

consistent consistent

ofa ofa

from from

shown shown

Although Although

system. system.

simi!ar simi!ar

of of

generated generated

UV-B UV-B

is is

of of

UV-formation UV-formation

~N~~ ~N~~

characteristic characteristic

2-Phenyl 2-Phenyl

piperidine-labile piperidine-labile

DNA, DNA,

singlet singlet

completely completely

distinguished distinguished

predominent predominent

radiation. radiation.

DNA DNA

and and

sirnilar sirnilar

function function

a a

consistent consistent

to to

exclusively exclusively

therefore, therefore,

2-Phenyl 2-Phenyl

Retinoic Retinoic

RYjıN"'·~ RYjıN"'·~

an an

pterin pterin

susceptible susceptible

to to

DNA DNA

of of

(SOD) (SOD)

causes causes

A A

in in

3H 3H

been been

by by

to to

the the

This This

the the

benzirnidazole benzirnidazole

(ROI) (ROI)

(a) (a)

O O

2 2 5-substituted 5-substituted

be be

was was

acid acid

transfer transfer

(X-XO) (X-XO)

S S

H H

substitutes, substitutes,

CH, CH,

oxygen oxygen

that that

worms worms

7. 7.

is is

on on

8. 8.

has has

to to

sunlight. sunlight.

presence presence

R: R:

R: R:

almost almost

oxygen oxygen

native native

it it

certain certain

results, results,

,,) ,,)

exposed exposed

single-stranded single-stranded

investigation investigation

V,...~~~COOH V,...~~~COOH

DNA-macromolecule DNA-macromolecule

the the

c~ c~

Figure Figure

on on

formation formation

specifically specifically

are are

modified modified

sulfonic sulfonic electron electron map map 2-Phenyl 2-Phenyl

sunscreen sunscreen

af28. af28.

aı;ıd aı;ıd

ura! ura!

and and

formation. formation.

engers engers

residues. residues. sitizer sitizer

singlet singlet oxidation oxidation

methyl methyl preparations, preparations,

An An

Figure Figure

gested gested

cross-links cross-links

of of

in in

position position

Adult Adult

found found

dismutase dismutase

mediates mediates

system system oxidase oxidase

ions ions

The The

· ·

5-

on on

re­

ac­

"' "'

ex­

and and

and and

can­

con­

pen­

-

cam­

(ben­

inter­

N N

activ­

cases, cases,

Quin­

found found

hydro­

or or

to to

(c) (c)

structure structure

hydroxyl hydroxyl

(c) (c)

effect effect

RNA RNA

and and

2-[(5,6,7,8-

dependent dependent

was was

greater greater

5-hydroxy­

sulfur sulfur

some some

significant significant

activity activity

halogenated halogenated

a a

m m

7) 7)

an an

enzyme enzyme

producing producing

a a

in in

co co

known known

has has

P450 P450

in in

Also Also

to to

and and

derivatives derivatives

polycyclic polycyclic

chemical chemical

EROD EROD

mutagenic mutagenic

are are

and, and,

BENZIMIDAZOLE BENZIMIDAZOLE

have have

(EROD) (EROD)

benzimidazoles benzimidazoles

(Figure (Figure

aliphatic aliphatic

superoxide, superoxide,

alpha-tocopherol alpha-tocopherol

led led

4. 4.

Thiabendazole, Thiabendazole,

(PROD) (PROD)

2

acid. acid.

OF OF

compound, compound,

of of

both both

as as

. .

Benzirnidazole, Benzirnidazole,

whose whose

LJJI LJJI

and and

effective effective

26

in in

proteins proteins

activate activate

NH NH

(thiabendazole, (thiabendazole,

.. ..

(b) (b)

compound compound

6), 6),

ultirnate ultirnate

drugs

nitrogen, nitrogen,

(BITN) (BITN)

oxidation oxidation

type type

cytochrome cytochrome

such such

are are

sulfur-free sulfur-free

of of

retinoic retinoic

(b) (b)

irnidazoles, irnidazoles,

formula formula

This This

arnines arnines

their their

0-deethylase 0-deethylase

. . and and

carbendazirn) carbendazirn)

ACTIVITY ACTIVITY

as as

activities

2

increase increase

and and

carbendazim carbendazim

(Figure (Figure

~ ~

~',/ ~',/

enzymes enzymes

0

to to

trans trans

species species

0-depentylase 0-depentylase

2

hepatic hepatic

retinoid retinoid

Püsküllü Püsküllü

P4501Al/2 P4501Al/2

lmidazole, lmidazole,

and and

H

such such

and and

all all

heterocyclic heterocyclic

microsomal microsomal

a a

forms, forms,

on on

(a) (a)

Chemical Chemical

a a

aromatic aromatic

göz~ göz~

metabolisrn metabolisrn

benzirnidazoles benzirnidazoles

These These

and and

6. 6.

5. 5.

oxygen oxygen

that that

Ala Ala

the the

quinolines quinolines

with with

(a) (a)

Figure Figure

includes includes

Süzen~ Süzen~ also also

oline oline

DERIVATIVES DERIVATIVES

Substances Substances

Recently Recently

carbons, carbons,

toxyresorufin toxyresorufin ities25. ities25.

Figure Figure

ANTIOXIDANT ANTIOXIDANT

with with ethoxyresorufin ethoxyresorufin

effective effective tetrahydro-5,5,8,8-tetramethyl-2-naphtalene)] tetrahydro-5,5,8,8-tetramethyl-2-naphtalene)]

carboxybenzimidazole carboxybenzimidazole

fere fere

tivity tivity

radical radical

116 116

active active hydracarbons hydracarbons

cerogenic cerogenic

thiabendazole) thiabendazole)

taining taining

cytochrome cytochrome

dose-dependent dose-dependent

monooxygenase monooxygenase

zimidazole zimidazole

pres·sion. pres·sion. bendazole bendazole

of of

on on

on on

by by

in­

in­

in­

are are

the the

cy­

117 117

and and

sys­

was was

also also

per­

pos­

sub­

con­

ben­

non­

, ,

to to

bear­

bind­

of of

living living

on on

on on

is is

35

results results

M M

interact interact

of of

of of

express­

?ı ?ı

lt lt

ali ali

was was

the the

extent extent

and and

inhibitors inhibitors

tissues tissues

monooxy­

patent patent

chain chain

to to

lipid lipid

be be

in in

10-4 10-4

The The

compounds compounds

mode mode

structure structure

aminopyrine aminopyrine

effects effects

. .

be be

dependent dependent

to to

occurring occurring

microsomes36_ microsomes36_

6

and and

oxidases

on on

large large

the the

methyl-[5-[[4(2-

)-NHCOCH3 )-NHCOCH3

and and

fused fused

is is

is is

to to

nature nature

a a

derivatives derivatives

N N

and and

peroxidation peroxidation

depending depending

3 3

found found

various various

of of

single single

effective effective

enzymes enzymes

to to

derivatives derivatives

ring ring

precise precise

that that

determine determine

ıo-

a a

in in

benzimidazoles benzimidazoles

known known

dependent dependent

variable variable

microsomes. microsomes.

are are

type, type,

in in

hepatic hepatic

lipid lipid

studied3

.--"' .--"'

at at

P450 P450

compounds compounds

of of

the the

activity activity

known known

can can

were were

The The

\ \

than than

in in

alsa alsa

of of

inhibition inhibition

have have

formula formula

additional additional

chemical chemical

P450 P450

imidazole imidazole

both both

lowered. lowered.

are are

with with

showed showed

that that

depends depends

been been

are are

series series

il il

of of

0--0NH 0--0NH

binding binding

hydroxylase hydroxylase

oxidised oxidised

antioxidant antioxidant

mixed-function mixed-function

more more

a a

the the

observed observed

as as

in in

dependent dependent

ability ability had had

tissue tissue

N-C N-C

of of

of of compounds compounds

P450 P450

differentially differentially

group group

which which

character. character.

results results

activities activities

groupings groupings

related related

that that

derivatives derivatives

which which

chemical chemical

ability ability

was was

indicate indicate

the the

the the

well well

and and

Significant Significant

containing containing

hepatic hepatic

j\ j\

\_J \_J

The The

cytochrome cytochrome

appreciably appreciably

on on

as as monooxygenase monooxygenase

The The

xenobiotics34. xenobiotics34.

The The

P450 P450

Release Release

observed observed

that that

be be

far far

nitrogen nitrogen

of of

NADPH-

levels levels

activities activities

carboxyl carboxyl

hydrocarbon hydrocarbon

regulated regulated

10. 10.

results results

aromatic aromatic

'iN 'iN

to to

lipophilic lipophilic

some some

therefore, therefore,

cytochrome cytochrome

N\_ N\_

N N

on on

the the

type type

compounds compounds

aryl aryl

and and

vitro potencies potencies vitro

C

zimidazoles zimidazoles

with with

of of

CONCLUSION CONCLUSION

fused fused N-demethylase N-demethylase

stitutents. stitutents. These These

showed showed

Organic Organic

their their

substitution substitution

genase genase

sible sible

structure. structure.

benzimidazole benzimidazole ing ing

hibitors hibitors

inhibition, inhibition,

hibition hibition

Benzimidazoles Benzimidazoles es es

the the

hibit hibit

depending depending

centrations. centrations.

ing ing

tochrome tochrome

oxidase oxidase In In

observed33_ observed33_

tems tems benzimidazole-2-yl]carbamate benzimidazole-2-yl]carbamate

numerous numerous

pyrimidinyl)-1-piperazinyl]carbonyl]-lH­

Figure Figure

found found

tathione. tathione.

2-

in in

of of

el­

ef­ re­

rat rat

di­

re­

in in

ke­

en­

ox­

2,2'­

and and

glu-

and and

2,2'­

glu­

host host

pro­

Both Both

-

vitae vitae

SOD SOD

lead­

in in

Anti­

result result

of of

of of

found found

the the

il il

ketone ketone

o o

of of

in in

and and

the the

a a

system. system.

as as

appears appears

reduced reduced the the

A. A.

action action

and and

af32. af32.

markedly markedly

activities activities

reductase reductase

nontoxic nontoxic

of of

important important

as as

was was

by by

reduce reduce

of of

et et

hand hand

catalase catalase

well well

catalase catalase

and and

Dicarbometh­

toxicity, toxicity,

the the

depression depression

>-NHCOCH3 >-NHCOCH3

enzyme. enzyme.

parasite. parasite.

less less

useful useful

N N

fariid. fariid.

dehydrogenase dehydrogenase

as as

antioxidant antioxidant 2 2

-

defence defence

(DEC) (DEC)

and and

against against

peroxidase31 peroxidase31

Nippostrongylus Nippostrongylus

(GPx) (GPx)

0

enzymes enzymes

activities activities

ketone ketone

the the

2

other other

measured measured

levels levels

metabolism metabolism

SOD, SOD,

2000 2000

on on

metabolism metabolism

4-(2-pyrimidinyl)-1-

H

the the

recorded recorded

--"' --"'

2,2' 2,2'

of of

found found

active active

benzimidazole benzimidazole

generated generated

glutathione glutathione

. .

formula formula

itself itself the the

major major

enzymes enzymes

appear appear

j j

inhibited inhibited

to to

the the

these these

to to

anthelminthic anthelminthic

the the

high high Srivastava Srivastava

parasite parasite

weak weak

38

been been

of of

an an

effect effect

against against

of of

was was

significant significant

suggesting suggesting

were were

On On

in in

of of

the the

il il

ROI ROI

o o

c c

on on

by by

on on

JJ3-119, JJ3-119, dismutase dismutase

the the

released released

of of

a a

the the

has has

peroxidase peroxidase

glı..tathione glı..tathione

toxic toxic

j j

10) 10)

prone prone

which which

protect protect

in in

25, 25,

to to

methyl-[5-[[ methyl-[5-[[

(GPx) (GPx)

2,2'-dicarbomethoxylamino-5,5'­

be be

lungs lungs

mode mode

also also

to to

observed

effect effect

and and

ketone ketone

~ ~

adverse adverse

present present

against against

activities activities

surroundings surroundings

antioxidant antioxidant

costitute costitute

Sci., Sci.,

ketone ketone

Chemical Chemical

appreciably appreciably

Inhibition Inhibition

due due

to to the the

species species

and and

diethylcarbamazine diethylcarbamazine

and and

carbonyl]-lH-

examined examined

species species

of of

(Figure (Figure

to to

presence presence

No No

parasite parasite

vitae vitae

compound. compound.

N N

9) 9)

glucose-6-phosphate glucose-6-phosphate

NHD~Nll NHD~Nll

might might

produced produced

their their

were were

y. y.

superoxide superoxide

were were

medium, medium,

ability ability

2,2'-dicarbomethoxylamino-5,5' 2,2'-dicarbomethoxylamino-5,5'

glutathione glutathione

weak weak

flariid flariid

9. 9.

A. A.

vitae. vitae.

the the

the the

the the

catalase catalase

liver liver

of of

was was

Pharm. Pharm.

of of

peroxidase peroxidase

an an

stud stud

the the

levels levels

J J

the the the the

agents, agents,

A. A. of of

and and of of

death. death.

oxygen oxygen

in in

oxygen oxygen

of of

immediate immediate

o o

(Figure (Figure

in in

of of

important important

to to

appeared appeared

role role exposure exposure

level level

catalase catalase

to to

understand understand

CO~HN--{ CO~HN--{

render render

the the

3

H

the the

brasiliensis, brasiliensis,

intestine intestine

thiabendazole thiabendazole dicarbomethoxylamino-5,5'-dibenzimidazolyl dicarbomethoxylamino-5,5'-dibenzimidazolyl active active

Figure Figure

compounds compounds

piperazinyl] piperazinyl]

another another evated evated

inhibited inhibited

active active

yl]carbamate yl]carbamate

oxylamino-5,5'-dibenzimidazolyl oxylamino-5,5'-dibenzimidazolyl To To

tone tone

zymes zymes glutathione glutathione

fect fect

dibenzimidazolyl dibenzimidazolyl

of of

nature nature

tecting tecting (GR) (GR)

due due

ing ing

dicarbomethoxylamino-5,5'-dibenzimidazolyl dicarbomethoxylamino-5,5'-dibenzimidazolyl

to to GPx GPx benzimidazolyl benzimidazolyl FABAD FABAD

filarial filarial

(G6PDH). (G6PDH).

GPx GPx

and and tathione tathione

less less

in in

The The

showed showed

combination combination

and and idants idants

), ),

is­

in­

ty­

al­

su­

MJ, MJ, M. M.

Ev­

and and

lnt., lnt.,

289-

hip­

the the

anti­

after after

from from

Sjoq­

mep­

path­

Arch. Arch.

Phar­

indol-

on on

by by

VanZ­

SF. SF.

Tartoni Tartoni

in in

in in

of of

T, T,

Metab., Metab.,

abilities abilities

new new

1998. 1998.

nervous nervous

Nagatsu Nagatsu

immune immune

of of

Biol. Biol.

157, 157,

Schauen­

P, P,

İşcan İşcan

Int. Int.

Neurosci. Neurosci.

and and

a a

Melatonin Melatonin

1910-1914, 1910-1914,

A, A,

Anticancer Anticancer

11,639-650, 11,639-650,

1996. 1996.

oxide oxide

cerebral cerebral

B, B,

M, M,

D, D,

the the

Naldrett Naldrett

Pang Pang

1993. 1993.

of of

C. C.

Flow Flow

isolated isolated

1998. 1998.

Sakakibara Sakakibara

function function

45, 45,

death death

Mal. Mal.

Trp-P-1 Trp-P-1

Physiol. Physiol.

cells, cells,

on on

temperature temperature

hyperoxide hyperoxide

central central

serotonin serotonin

359-384, 359-384,

T, T,

Scand., Scand.,

FA, FA,

Influence Influence

Naoi Naoi

Schersten Schersten

system, system,

nitric nitric

GM, GM,

]. ].

Vermeij Vermeij

Behl Behl

Hofer Hofer

cell cell

oxidation oxidation

of of

44-51, 44-51,

Blood Blood

I. I.

scavenging scavenging

Effect Effect

during during

56, 56,

tumour, tumour,

S, S,

Tampieri Tampieri

T, T,

on on

the the

P, P,

Can-Eke Can-Eke

kidney kidney

Toxa·col./ Toxa·col./

the the

GJ, GJ,

223-232, 223-232,

Brain Brain

amine amine

primaquine primaquine

2071-2077, 2071-2077,

(Tokyo) (Tokyo)

1994. 1994.

vasodilatation vasodilatation

1997. 1997.

22, 22,

PC12h PC12h

O. O.

in in

E, E,

Can. Can.

AI, AI,

Biochem. Biochem.

7, 7,

Phsiol. Phsiol.

skatolyl skatolyl

on on

Meli Meli

by by

Brown Brown

cites cites

in in

compounds compounds

melatonin melatonin

Cereb. Cereb.

333, 333,

CC. CC.

immune immune

radical radical

Res. Res.

of of

Watanabe Watanabe

Bull., Bull.,

Felsner Felsner

as as

of of

Blauw Blauw ]., ].,

CS, CS,

Oxidation Oxidation

LM, LM,

Galatulas Galatulas

Widmann, Widmann,

the the

drug, drug,

Acta. Acta.

Pettersson Pettersson

107-117, 107-117,

103-311, 103-311, quinine, quinine,

Takahashi Takahashi

A, A,

rats, rats,

A, A,

Jonsson Jonsson

The The

production production

G. G.

Ruberto Ruberto

T, T,

damage damage

3, 3,

PC, PC,

mRNA mRNA

U, U,

in in

stress-induced stress-induced

L, L,

Neurobiology, Neurobiology, Pang Pang

W, W,

MR, MR,

and and

heterocyclic heterocyclic Y. Y.

Pharmacol., Pharmacol., 1996. 1996.

1991. 1991.

Chem. Chem.

mediated mediated

G, G,

chemicals, chemicals,

112, 112,

action action

1993. 1993.

Pharm. Pharm.

a a

Büyükbingöl Büyükbingöl

in in

is is

Piandatosi Piandatosi

peroxidation peroxidation

Biochem. Biochem.

Wofler Wofler

Neuroreport., Neuroreport.,

evolution evolution

S, S,

ZM, ZM,

radical radical

of of

peroxidase-catalysed peroxidase-catalysed

), ),

Antioxidative Antioxidative

Lagrimini Lagrimini

Chang Chang

Skutella Skutella

Bassa Bassa

Nagatsu Nagatsu

Signals, Signals,

Identification Identification

Serotonin-induced Serotonin-induced

direct direct

other other

Nilsson Nilsson

Dryhurst Dryhurst

1996. 1996.

1996. 1996.

Baggio Baggio

PM, PM,

the the

Oxidative Oxidative

Chem. Chem. 537-549, 537-549,

Nakano Nakano

Liu Liu H. H.

F, F,

a a

acid, acid,

lipid lipid

T, T,

the the

cells, cells,

radical, radical,

183-186, 183-186, chloroquine, chloroquine,

IG, IG,

anti-nephritic anti-nephritic

oxidative oxidative

Svensson Svensson

V, V,

TA, TA,

Melatonin Melatonin

2673-2675, 2673-2675,

reperfusion reperfusion

M, M,

Süzen Süzen

Biol. Biol.

Immunol., Immunol.,

Progress Progress

forearm forearm

T, T,

effect effect HL, HL,

PA. PA.

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