SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL EVALUATION ...

1 downloads 0 Views 606KB Size Report
Jan 31, 2011 - (Spectrum RXI) spectrometer (µ in cm-1) using KBr discs. 1H-NMR spectra .... Pharmaceutical Sciences 2006: 68(6):719-725. 8. Silverstein RM ...

Chandramohan et al., IJPSR, 2012; Vol. 3(5): 1516-1519 IJPSR (2012), Vol. 3, Issue 05

ISSN: 0975-8232 (Research Article)

Received on 31 January, 2011; received in revised form 27 February, 2012; accepted 28 April, 2012

SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL EVALUATION OF SOME NOVEL THIAZOLIDINONES DERIVATIVES S. Chandramohan*1, R. ElayaRaja 1, S. Thiripura Salini 1, A. Elavarasan 2 and R. Senthil Kumar 2 Department of Chemistry, PRIST University 1, Vallam, Thanjavur-613 403, Tamil Nadu, India Department of Chemistry, Ponnaiyah Ramajayam Engineering College 2, Vallam Thanjavur-613 403, Tamil Nadu, India ABSTRACT Keywords: Anti bacterial, Schiff base, Thiazolidinone Correspondence to Author: S. Chandra mohan Assistant Professor, Department of Chemistry, PRIST University, Vallam, Thanjavur -613 403, Tamil Nadu, India

The main objective of the medicinal chemistry is to synthesize the compounds that show promising activity and therapeutic agents with lower toxicity. Thiazolidinone are very useful compound with well known biological activities. Notable among these are antibacterial, antiviral, analgesic, antiinflammatory, antitubercular and anticonvulsant. In the current research work, three novel substituted thiazolidin-4-one derivatives were prepared from the corresponding Schiff bases and 2-mercapto acetic acid in benzene using Stark and Dean Apparatus. The identification and characterization of synthesized compounds were carried out by Elemental analysis, FT-IR and NMR data to ascertain that all synthesized compounds were of different chemical nature than the respective parent compound. The synthesized compounds showed good antibacterial activity against Escherichia Coli, Staphylococcus, Pseudomonas aeruginosa and Salmonella typhi.

INTRODUCTION: 4-Thiazolidinones have been reported to show a broad spectrum of biological activities. Notable among these are antibacterial 1, antiinflammatory 2, antitubercular 3, anticonvulsant 4, local anaesthetic/anti HIV 5 and anthelmintic activity 6, 7 . The pharmacological properties of 4-thiazolodinones encouraged our interest in synthesizing several new compounds featuring various heterocyclic rings, attached to 4-thiazolodinone moieties. As a part of our aim to search for biologically active heterocycles containing sulphur and nitrogen. We have now synthesized a series of some novel thiazolidin-4-one derivatives. The bromo and hydroxy substitutions at para position improve antimicrobial activity. Therefore, it was though worth wile to synthesize some new thiazolidinone containing compounds and evaluate antibacterial potential.

MATERIALS AND METHODS: All the reagents and solvents used were of laboratory grade. The melting point of synthesized compounds were determined by open capillary method and were uncorrected. The purity of the compounds was checked by thin layer chromatography (TLC). IR spectra 8 were obtained on a Fourier transform Infrared (FTIR) Perkin Elmer (Spectrum RXI) spectrometer (µ in cm-1) using KBr discs. 1H-NMR spectra 9 were recorded in MeOD with tetramethylsilane (TMS) as the internal standard at 500MHz on a Bruker DMX-500MHz spectrometer. The chemical shifts are reported in parts per million. The elemental analysis of compounds was performed on Elementar Vario EL III Carlo Erba-1108 elemental analyzer. Scheme of synthesis: Three novel thiazolidinones viz., 2-(4-bromophenyl)-3-(4-hydroxyphenyl)thiazolidin-4one (compound 1), 3-(4-hydroxyphenyl)-2-styrythia-

Available online on www.ijpsr.com

1516

Chandramohan et al., IJPSR, 2012; Vol. 3(5): 1516-1519

ISSN: 0975-8232

SCHEME 3

zolidin-4-one (compound 2), 2, 3-bis(4-hydroxyphenyl)thiazolidin-4-one (compound 3) were synthesized by using the following schemes I, II, III from the corresponding Schiff bases. SCHEME 1

COMPOUND 3

Preparation of Schiff Bases:

COMPOUND 1 SCHEME 2

Preparation of 4-(4-bromobenzylidene amino)phenol: About 10g of 4-bromobenzaldehyde (0.05mol) and 6g of 4-aminophenol (0.05mol) was mixed with 40ml of ethanol and refluxed for 5hrs. The crude product obtained was recrystallised from ethanol. Yield: 88.0% , M.P.129oC. Preparation of 4-(3-phenylallylidene amino)phenol: About 7ml of trans-cinnamaldehyde (0.05mol) and 6g of of 4-aminophenol (0.05mol) was mixed with 40ml of ethanol and refluxed for 5hrs. The crude product obtained was recrystallised from ethanol. Yield: 65.0% , M.P.124oC. Preparation of 4-(4-hydroxybenzylidene amino) phenol: About 6g of 4-hydroxybenzaldehyde (0.05mol) and 6g of 4-aminophenol (0.05mol) was mixed with 40ml of ethanol and refluxed for 5hrs. The crude product obtained was recrystallised from ethanol. Yield: 82.0% , M.P.120oC.

COMPOUND 2

Available online on www.ijpsr.com

1517

Chandramohan et al., IJPSR, 2012; Vol. 3(5): 1516-1519 Preparation of Thiazolidinones: Preparation of 2-(4-bromophenyl)-3-(4-hydroxy phenyl)thiazolidin-4-one: (Compound 1): About 1.33g of 4-(4-bromobenzylidene amino)phenol (0.05mol), 25ml of benzene and 4.3ml of 2-mercapto acetic acid was taken in a 250ml R.B. flask. The mixture was refluxed on water bath using Stark and Dean apparatus for 12hrs. After refluxing the mixture was cooled and poured into ice water. The upper organic layer was washed successively with aq. sodium bicarbonate and water. The organic layer id dried and concentrated . The crude product obtained was recrystallized from ethanol. Yield: 59.0% , M.P.120oC. Preparation of 3-(4-hydroxyphenyl)-2-styrythiazolidin -4-one: (Compound 2): About 2.3g of 4-(3-phenylallylidene amino)phenol (0.01mol), 25ml of benzene and 4.3ml of 2-mercapto acetic acid was taken in a 250ml R.B.flask. The mixture was refluxed on water bath using Stark and Dean apparatus for 12hrs. After refluxing the mixture was cooled and poured into ice water. The upper organic layer was washed successively with aq. sodium bicarbonate and water. The organic layer id dried and concentrated . The crude product obtained was recrystallized from ethanol. Yield: 49.0% , M.P.118oC. Preparation of 2, 3-bis(4-hydroxyphenyl)thiazolidin-4one:

ISSN: 0975-8232

(Compound 3): About 1.97 of 4-(4-hydroxybenzylidene amino) phenol (0.01mol), 25ml of benzene and 4.3ml of 2-mercapto acetic acid was taken in a 250ml R.B.flask. The mixture was refluxed on water bath using Stark and Dean apparatus for 12hrs. After refluxing the mixture was cooled and poured into ice water. The upper organic layer was washed successively with aq. sodium bicarbonate and water. The organic layer id dried and concentrated . The crude product obtained was recrystallized from ethanol. Yield: 40.0% , M.P.94oC. Antimicrobial Screening 10: All the synthesized compounds were screened for antimicrobial activity against Escherichia Coli, Staphylococcus, Pseudomonas aeruginosa and Salmonella typhi using disc method. In disc method, a known weight of each of the test compounds, 50mg, was dissolved in minimum quantity of DMSO and it was impregnated in a sterile filter paper disc of size 4mm. It was then allowed to dry. The discs dipped only in DMSO, after drying, were used as the control. The plates, containing nutrient agar were used. They were seeded with different organisms at concentrations of 2-3X10-7 in Colony Forming Unit (CFU) using sterile swab. The discs containing the samples were placed at different positions using fine pointed forceps. The plate were incubated at 37ºC for 24hrs., followed by measuring the zones of inhibition . The above observation made under sterile condition. RESULTS AND DISCUSSION: The elemental analysis of the synthesized compounds 1, 2 and 3 are given in table 1.

TABLE 1 : ELEMENTAL ANALYSIS OF COMPOUNDS 1, 2 AND 3 Elemental Analysis(%) Compound No. Compound 1 Compound 2 Compound 3

Mol. Formula C15H12BrNO2S C17H15NO2S C15H13NO3S

Mol.Wt 350.23 297.37 287.33

Calculated H 3.45 5.08 4.56

C 51.44 68.66 62.70

N 4.00 4.71 4.87

C 51.46 68.64 62.68

Found H 3.47 5.10 4.58

N 4.04 4.73 4.85

Spectral Data of Compounds 1, 2 and 3 are given below:

1

Spectral data of compound 1:

Spectral data of compound 2:

IR(KBr)cm-1: 621.86(C-S), 1654.84(C=O), 1319.77(C-N), 3166.83(-OH)

IR(KBr)cm-1: 698.37(C-S), 1658.48(C=O), 1378.56(C-N), 3435.12(-OH)

HNMR: δ4.9(S,1H), δ3.33(S,2H), δ6.21(S,1H), δ6.78(d,2Ho), δ6.98(d,2Hm), δ7.47(d,2Ho), δ7.31(d,2Hm)

Available online on www.ijpsr.com

1518

Chandramohan et al., IJPSR, 2012; Vol. 3(5): 1516-1519

ISSN: 0975-8232

1

1

Spectral data of compound 3:

The following table (Table 2) presents the data of antimicrobial effect of the compounds 1, 2 and 3.

HNMR: δ5.0(S,1H), δ5.95(S,1H), δ3.33(S,2H), δ7.187.31(m,5H,Ar-H), δ6.74(d,2Ho), δ6.75(d,2Hm), δ7.05 (d,1H1,CH1==CH), δ7.10(d, 1H2,CH=CH2)

HNMR: δ5.0(S,1H), δ3.33(S,2H), δ6.1(S,1H), δ6.687.58(m,8H Aromatic)

IR(KBr)cm-1: 668.54(C-S), 1609.76(C=O), 1383.32(C-N), 3436.75(-OH) TABLE 2: EVALUATION OF ANTIBACTERIAL EFFECT OF COMPOUNDS 1, 2 AND 3 Compound (Erythromycin) Standard Compound 1 Compound 2 Compound 3

Weight of the Compound (µg/ml) 30 50 50 50

Escherichia Coli 29 14 15 16

Radius of Inhibition zone (mm) Salmonella typhi Pseudomonas aeruginosa 19 24 15 11 13 14 11 12

Analysis of the data in Table 2 shows that the synthesized compounds have fairly good antibacterial activity which is however less than that of the activity of the standard drug Erythromycin CONCLUSION: The present work describes the synthesis of Schiff’s bases and their thiazolidinone derivatives with their antibacterial activities. The structures of the synthesized compounds were assigned on the basis of the spectral data. The IR spectra and 1HNMR spectra of the synthesized compounds showed the expected absorption frequencies leading the support to the assigned structures. The synthesized compounds were screened for antibacterial activity, it showed that the synthesized compounds possess fairly good antibacterial activity. REFERENCES 1.

2.

Kucukguzel G, Oruç EE, Rollas S, Sahin F and Özbek A: Synthesis, Characterization and biological activity of novel 4thiazolidinones, 1,3,4-oxadiazoles and some related compounds. Eur. J. Med. Chem. 2002; 37: 197-206. Brun G, Ottanà R, Maccari R , Barreca ML, Rotondo A, Rossi A, Chiricosta G, Di Paola R, Sautebin L, Cuzzocrea S and Vigorita MG:5-Arylidene-2-imino-4-thiazolidinones: Design and

Staphylococcus aureus 20 13 11 14

synthesis of novel antiinflammatory Agents. Bioorganic & Medicinal Chemistry .2005; 13: 4243–4252. 3. Handan ALTINTAS, ¨Oznur ATES, Seher B_IRTEKS¨OZ, G¨ulten ¨OT¨UK, Meltem UZUN, Dilek S_ATANA: Synthesis of Mannich Bases of Some 2,5-Disubstituted 4-Thiazolidinones and Evaluation of Their Antimicrobial Activities. Turk J Chem .2005;29: 425 - 435. 4. Srivastava SK, Srivastava SH and Srivastava SD: Synthesis of 5arylidene-2-aryl-3(2-chlorophenothiazinoacetamidyl)-1,3-thia zolidin-4-ones as anticonvulsant agents. J.Indian.Che.Soc.2000; 77:104-105. 5. Rawal RK, Tripathi R, Kulkarni S, Paranjape R, Katti SB, Pannecouque C, et al. 2-(2,6-Dihalo-phenyl)-3-heteroaryl-2ylmethyl-1, 3-thiazolidin-4-ones: Anti-HIV agents. Chem Biol Drug Des. 2008;72:147–54. 6. Kucukguzel G , Kocatepe A , De Clercq E , Sahin F and Gulluce M: Synthesis and biological activity of 4-thiazolidinones, thiosemicarbazides derived from diflunisal hydrazide. European Journal of Medicinal Chemistry 2006; 41(3): 353-359. 7. Vagdevi HM, Vaidya VP, Latha KP and Padmashali B: Synthesis and pharmacological examination of some thiazolidinone derivatives of naphtho[2,1- b ]furan, Indian journal of Pharmaceutical Sciences 2006: 68(6):719-725. 8. Silverstein RM and Morrill TC:Spectrophotometric Identification of Organic Compounds,John Wiley and Sons,New York,Edition 4,1981:312. 9. Silverstein RM and Morrill TC:Spectrophotometric Identification of Organic Compounds,John Wiley and Sons,New York,Edition 4,1981:192. 10. Sahm DF: A Manual of Clinical Microbiology. ASM, Washington, Edition 5, 1991, 1105.

******************************

Available online on www.ijpsr.com

1519

Suggest Documents