RESEARCH ARTICLE Radhika Kalate et al.

/ IJIPSR / 1(1), 2013, 108-116

Department of Pharmaceutical Chemistry ISSN (online) 2347-2154

International Journal of Innovative

Pharmaceutical Sciences and Research
www.ijipsr.com

SYNTHESIS ANTICONVULSANT AND ANTI MICROBIAL EVALUATION OF

SUBSTITUTED FURAN DERIVATIVES
1
Radhika Kalate*, 2Shiny Geore, 3Vijeyaanandi, 4Sanjay Varma

Department of Pharmaceutical chemistry, Vels University Chennai.

ABSTRACT
In the present study a new series of 2-(naphtha[2,1-b] furan -2yl)-ethane-1,2-dione derivatives were synthesized by the
incorporation of2(naphtha [2,1-b]furan2yl)acetic acid with appropriate aldehydes. The chemical structures of the
synthesized compounds were confirmed by means of IR,1H NMR, Mass spectral and elemental analysis. All the
synthesized compounds were evaluated for antimicrobial and anticonvulsant activity by MES and PTZ method by using
phenytion(25 mg/kg) as standard drug The synthesized compounds 3c,3d,3e,3g was found to exhibit activity when
compared with standard.

Key words: Naphtho [2, 1-b] furan, Anticonvulsant, MES.

CorrespondingAuthor:

Radhika Kalate
Assistant Professor
Pharmaceutical chemistry
Email: radhika.pharmaradhikakalate@gmail.com
9963125941

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RESEARCH ARTICLE Radhika Kalate et al. / IJIPSR / 1(1), 2013, 108-116
Department of Pharmaceutical Chemistry ISSN (online) 2347-2154

INTRODUCTION [1]
Furan is a heterocyclic organic compound, consisting of a five membered aromatic ring with four
carbon atoms and one oxygen. It is colour less, flammable, highly volatile liquid with a boiling point
close to room temperature.

Literature [2,3,4] has suggested that naphtho[2,1-b]furan derivatives are reported to posses wide
spectrum of biological activities like antifungal, antimicrobial, antitumor, antihelmintic activity,
antiinflamatory, antibacterial, antimalarial, anti ulcer, anti tubercular, anticancer, antiviral.

The aim of the present work describes the synthesis(Scheme 1) of 2hydroxy naphthaldehyde by
Reimer tiemer reaction and finally the titled compounds were synthesized by the incorporation of
2(naphtho[2,1-b] furan 2yl)acetic acid with a series of aromatic aldehydes and the newly synthesized
compounds were evaluated for their anti convulsant activity .All the experiment protocols were
reviewed and accepted by the institutional Animal ethical committee(IAEC) prior to the initiation of
the experiment.

MATERIALS AND METHODS

The melting points were taken in open capillary tube and are un corrected 1H NMR spectra were
recorded on 400 MHZ-Joel GSX 400 using DMSO-d6 as solvent, mass spectra were recorded on
Shimadzu GC-MS QP 5050A.The IR spectra were recorded on ABB Bomem FTIR spectrometer
MB104 with KBR pellets.The purity of compounds was ascertained by thin layer chromatography
(TLC) on precoatedaluminium sheets(silica gel 60 F)and visualized by exposure to iodine vapours.
Elemental analysis was performed using Dumas method. The pharmacological evaluation was
conducted at Vels college of pharmacy, Chennai, after obtaining clearance from institutional animal
ethics committee. The physical data of the synthesized compounds was described in (Table 1).

Synthesis of naphtho[2,1-b]furan-2-carboxylic acid (2a)

2 hydroxyl-1-naphthaldehyde(0.03mol) was dissolved in the mixture of bromo acetic

acid(0.03mol),anhydrous potassium carbonate(0.3mol) and acetone(50ml) this solution was heated
under reflux for 24h.The reaction mixture was filtered and the product was recrystallised from ethanol

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RESEARCH ARTICLE Radhika Kalate et al. / IJIPSR / 1(1), 2013, 108-116
Department of Pharmaceutical Chemistry ISSN (online) 2347-2154
Synthesis of 1 (substituted phenyl)-2-(naphtho[2,1-b]furan-2yl)-ethane-1,2-dione(3a-3e)

2(naptho[2,1]furan2yl)acetic acid(0.004mol) was dissolved in the solution containing hot ethanol and
sodium hydroxide(1g). To the above solution appropriate aldehydes (1 g) were added with constant
stirring for 2h at 50-55˚C and cool water was added.The resultant solution was filtered and the
precipitate was recrystallised with appropriate solvent.

1-(3methoxy phenyl)-2-(naphtha [2,1-b] furan -2yl)-ethane-1,2-dione (3a)

IR KBr 3032(Ar) ,1693 (C-O ,Stretch) ,3585(C=O, Stretch) ,3300(C-H, Stretch) 1H NMR (DMSO) δ
ppm 7.32-7.67(m,6H),7.59(s,H) 7.05-7.67(m,7H), 3.73(m,3H,OCH3) mass(m/e) 330.09[M+] ,
331.09[M+1].

1-(2,4chloro phenyl)-2-(naphtha [2,1-b] furan -2yl)-ethane-1,2-dione (3b)

IR KBr 3089(Ar), 1050(C-O, Stretch), 3318(C=O Stretch) , 756(C-Cl) 1H NMR δ ppm 7.32-
7.67(m,6H), 7.59(s,1H), 7.39-7.69(m,3H)mass (m/e) 368 [M+], 369 [M+1].

1-(4-dimethyl amino phenyl)-2-(naphtha [2,1-b] furan -2yl)-ethane-1,2-dione(3c)

IR KBr 3043 (Ar), 986 (C-O Stretch) ,3489 (C=O), 1460 (C-N) 1H NMR δ ppm 7.32-7.67(m,6H),
7.59(s,1H), 6.49-7.25(m,10H),mass (m/e) 343 [M+], 344[M+1].

1-(3chloro phenyl)-2-(naphtha [2,1-b] furan -2yl)-ethane-1,2-dione(3d)

IR KBr 3064 (Ar) ,1068 (C-O),3589 (C=O),659 (Cl),1H NMR δ ppm 7.32-7.67(m,6H), 7.59(s,H),
7.39-7.69(m,4H) mass (m/e) 334 [M+],335[M+1].

1-(3chloro phenyl)-2-(naphtha [2,1-b] furan -2yl)-ethane-1,2-dione(3e)

IR KBr 3072 (Ar),859 (C-O), 3462 (C=O), 659 (Amine) ,1H NMR δ 7.32-7.67(m,6H), 7.59(s,1H),
7.32-8.38(d,4H)mass (m/e) 329[M+],330[M+1].

Anti -convulsant activity by maximal electro shock seizure test[11]

Groups of 8-10 animals were used per dose of a drug.Eletrical stimulation is applied via corneal or
electrodes with a stimulator that either delivers constant current at a frequency of 50-60/sec.The

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RESEARCH ARTICLE Radhika Kalate et al. / IJIPSR / 1(1), 2013, 108-116
Department of Pharmaceutical Chemistry ISSN (online) 2347-2154
electrodes are moistened with a saline solution before application.All the animals are stimulated with
the same supra maximal current strength that is usually 2-5 times the thresh hold current strength.With
constant current stimulators ,typical stimulation parameters include 150 Ma in mice ,50-60/sec
current delivered via ear corneal electrodes for sec25,26 with constant voltage stimulators ,250 V is
used.The resultant seizure passes through various phases of tonic limb flexion of about 1.5 sec
duration followed by phase of tonic limb extension lasting about 10 sec and finally followed by a
variable short clonicinterval.

Supressionof tonic hind limb is taken as a measure of efficacy in this test .Anticonvulsant potency is
determined by calculation of its anticonvulsant ED50 for suppression of tonic hind limb
extension.Phenytoin is used as standard drug,saline is used as control,

The newly synthesized compounds were evaluated for their anti convulsant activity by maximal
eletroshock method(MES),phenytoin is used as standard drug.The data of activity is mentioned in
Table2.

Anticonvulsant screening by PTZ method[10]

Pentylenetetrazole(PTZ) was used as convulsant. PTZ was dissolved in normal saline. The mice were
divided into groups of six each, keeping the gropup weight as equal as possible. All the synthesized
compounds( 3a-3g)were suspended in 2% CMC. The test compounds were injectedintraperitoneally
into each group. The control animals were injected with vehicle only. Thirty min later, for the
administration of either vehicle or test compounds, the animals were injected with
Pentylenetetrazole(90mg/kg), this dose is shown to produce convulsions in all untreated mice and
these animals exhibited 100% mortality during 24h. No protected animals in each group was recorded.

ANTIBACTERIAL EVALUATION

The antibacterial activity of synthesizedcompounds was carried out against various micro-organisms
namely:

1. Staphylococcus aureus (gram positive bacteria)

2.E.coli(gram negative bacteria)

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RESEARCH ARTICLE Radhika Kalate et al. / IJIPSR / 1(1), 2013, 108-116
Department of Pharmaceutical Chemistry ISSN (online) 2347-2154
3. Bacillus subtilis(gram positive bacteria)

4.Pseudomonasaeruginosa(gram negative bacteria)

Preparation of nutrient agar

Nutrient agar serves as the basal medium for the growth of organisms. The composition is as follows:

1. Peptone (Bacteriological) 10 gm

2. Beef extrat(Bacteriological) 0.5gm

3. Sodium chloride (Bacteriological) 0.5 gm

4. Agar (Bacteriological) 20 gm

5. Distilled water up to 1000ml

Nutrient agar was prepared by dissolving all the solids in water and pH adjusted to 6.8, autoclaved at
151/inch2 pressure for 20 min.

Standard drug: Chloramphenicol (100 µg/ ml)

Test: 3a-3g

Control: DMF

Antibacterial activity by Cup plate method [12]

The in vitro antibacterial activity was carried out against 24 hr old cultures of bacteria by cup plate
method. The compounds were tested at a concentration of 100µg/ml .The solution of
Chloramphenicol 100µg/ml was prepared and it is used as standard. Nutrient agar was used as culture
medium & DMF was used as solvent control. Laminar airflow bench was swapped with 70 % alcohol
and UV lamp was switched on. After 30 min, the UV lamp was switched off. All the reagents media,
inoculums and glassware were placed in laminar airflow bench observing all aseptic conditions. The
plates were inoculated within minutes of the preparation of suspension, so that the density does not
change. A sterile cotton swab over was dipped into the suspension and the medium was inoculated by
even streaking of the swab over the entire surface of the plate in three directions. After the inoculums
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RESEARCH ARTICLE Radhika Kalate et al. / IJIPSR / 1(1), 2013, 108-116
Department of Pharmaceutical Chemistry ISSN (online) 2347-2154
had dried, cups of diameter 6mm were made in the agar plate with a sterile cork borer. The drugs
solutions were added to these cups with a micropipette and the plates were then incubated at 37◦C for
24 hours. The diameter of the inhibition of growth of the microorganisms after 24 hrs was measured
as the zone of inhibition in millimeters(Table4).

RESULTS AND DISCUSSION

The present aim of the study is to synthesize 1 (subtituted phenyl) -2-(naphtha[2,1b]furan-2yl)-ethane-
1,2-dione by the incorporation of 2(naptho[2,1]furan2yl)acetic acid with appropriate aldehydes.

The structures of newly synthesized compounds were confirmed by their spectral data .IR spectra of
the compounds and their structure was further supported by their 1H NMR spectral data. Physical data
of the compounds is listed in Table1,Some of the. Naphtho[2,1-b]furan derivatives 3(c), 3(d), 3(e) has
shown anticonvulsant activity when compared with the standard has listed in Table2 and 3 . The
compound (3g) showed good activity against Staphylococcus aureus and Bacillus subtilis at 100 µg/ml
when compared to standard drug chloramphenicol, and (3b) showed good activity against E.coliat 100
µg/ml and (3a) showed good activity against Pseudomonas aeruginosawhen compared to standard
(Table 4).

Table 1: Physical data of the synthesized compounds

Melting
Compound R Mol.Formula Mol.Wt Yield%
point
C7 H8 O
3a C21 H 14O4 330 60 170 ̊C
C6 H4 Cl2
3b C20 H 10O3 Cl2 368 54 141 ̊C
C7 H11 N
3c C22 H 17O3 N 343 70 181 ̊C
C 6H 5Cl
3d C 20H 11O 3Cl 334 66 132 ̊C
C 6H5NO2
3e C20 H 11O 4N 329 55 150 ̊C

3f C9H8O C20 H13 O3 358.16 50 158˚C

3g C7H6O C20 H11 O3 316.11 48 150˚C

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RESEARCH ARTICLE Radhika Kalate et al. / IJIPSR / 1(1), 2013, 108-116
Department of Pharmaceutical Chemistry ISSN (online) 2347-2154
Fig: 1 Schematic representation of the synthesized compounds

CHO
OH

BrCH2COOH
COOH
O
K2 CO3
1
2

NaOH R H

O O
O
3a-3g

Table 2 : Anticonvulsant activity of synthesized compounds by MES method

Compound
Flexion Extension Clonus stupor Mortality%
(100 mg/kg)

3a 2.93 +0.53 9.31+ 0.52 3.19+0.24 95+0.32 0

3b 3.54 +0.47 11.73 + 0.4 2.92+ 0.31 99 + 0.16 0

3c 0.29 + 0.32** 8 .93+0.41 3.02 + 0.11 97 + 0.23 0

3d 1.83 +0.33*** 7.02 + 0.4 1.51 + 0.04 94 +0.24 0

3e 0.51 + 0.17 8.54 +0.21 2.53 +0.20 100+0.4 0

Control
4.61 +0.57 12.05 +0.12 3.26+0.45 120 +0.25 0
(2% CMC)
Phenytoin
1.85 +0.34 7.24 +0.56 1.56 +0.21 94+0.32 0
(25mg/kg)
One way ANOVA followed by Dunnet’s 't' test. Values are expressed in mean ± SEM (n = 6)
*** = P<0.001, ** = P<0.01, * = P<0.05.

Table 3: Anticonvulsant activity of synthesized compounds by PTZ method

Onset of clonic
Compound Treatment
convulsions
3a 100 mg/Kg 382.5±11.6
3b 100 mg/Kg 100.3±9.4
3c 100 mg/Kg A
3d 100 mg/Kg A
3e 100 mg/Kg A
Control 100 mg/Kg 109.5±9.8
Ethosuximide 150mg/Kg A
*P<0.05 when compared to control
A= Absence of seizure

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Department of Pharmaceutical Chemistry ISSN (online) 2347-2154
Table 4: Antibacterial activity of synthesized compounds by cup plate method

Compound Treatment Zone of inhibition in mm

E. coli B. subtilis P. aeruginosa S. aureus

3a 50 µg/ml 12 15 16 20

100 µg/ml 15 22 23 23

3b 50 µg/ml 19 14 15 19

100 µg/ml 22 21 20 21

3c 50 µg/ml 18 12 15 17

100 µg/ml 21 24 21 21

3d 50 µg/ml 17 15 14 18

100 µg/ml 21 22 19 20

3e 50 µg/ml 19 14 16 17

100 µg/ml 22 20 21 20

3f 50 µg/ml 18 16 13 18

100 µg/ml 20 22 18 23

3g 50 µg/ml 18 17 15 21

100 µg/ml 19 25 22 25

chloramphenicol 100 µg/ml 30 30 30 29

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RESEARCH ARTICLE Radhika Kalate et al. / IJIPSR / 1(1), 2013, 108-116
Department of Pharmaceutical Chemistry ISSN (online) 2347-2154
ACKNOWLEDGEMENT

The authors are thankful to Velsuniversity,Chennai for providing the infrastructure and facilities.The
authors are also thankful to Indian institution of technology for providing spectral data

REFERENCES

1. http://en.wikipedia.org/wiki/Furan
2. Joshi S.D ,Ashwini.J, Vagdevi .H, Vaidya.V.P. Synthesis and antimicrobial evaluation of some
new pyrrolylnaphtho[2,1-b]furan derivatives, Indian J.Pharma.Educ.Re, 2010; 44:481.
3. Diana patriza, Carbone.A, Barraja.P, Kelter.G, Fiebig H. Synthesis and antitumor activity of
2,5bis(3’indoyl)furans and 3,5-bis(3’-indoyl)isoxazolesnortopsentin analogues . Bio.org Med
Chem.2010; 18:4524.
4. Bahl.B.S. Advanced organic chemistry, pg no 1210-1212.
5. Dodd.M.C, Stillman.W, Martha.R, Catherene.C. Invitro bacteriostatic action of some simple
furan derivatives, J.Pharmacology.2010; 22:141-145
6. Behrouzi-Fardmoghadam M, Poorrajab F, Ardestani SK, Emami S, Shafiee A, Foroumadi A.
synthesis and in vitro anti-leishmanial activity of 1-[5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-
yl]- and 1-[5-(5-nitrothiophen-2-yl)-1,3,4-thiadiazol-2-yl]-4-aroylpiperazines.Bioorg Med
chem ,2008; 16: 15.
7. Vagdevi.H.M, Ravindra.K, Vagdevi.H, Vaidya. Synthesis antimicrobial and anti inflammatory
activities of 1,3,4 oxadiazoles linked to naphtha[2,1-b]furan, Indian J Chem,2006; 45: 2506-
2511.
8. Chakravarthy.E ,Geeta.B, Srinivasulu.D, Ugandhar.V. Synthesis of 2-(5 azido-5 deoxy β D
ribofuranosyl)-4-methyl-5-nitro-1,2,3triazole, Indian J Chem,2006; 45: 1920-1923.
9. Rajitha.B, NaveenKumar.V. Efficient synthesis of 3-(4-methyl-3-phenyl-furo[3,2-c]quinoline2
carbonyl)-chromen 2-ones under microwave irradiation, Indian J Chem, 2006; 45: 1995-
1957.
10. Silambujanaki.P, Chitra.V, SumaKumari, Raju.D. Anticonvulsant activity of methanolic extract
of Buteamonosperma leaves, RJPBCS, 2010; 1: 431.
11. Gupta.SK. Drug screening methods. 93-94.

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