Asian J. Research Chem. 4(1): January 2011
www.ajrconline.org
ISSN 0974-4169 RESEARCH ARTICLE
Synthesis, Characterization and Antimicrobial Activity of A 5(4-(4Substituted)Aminobenzylidine)Thiazolidine-2,4-Dione Derivatives Suresh Rajput1, Dharamveer Sisodia1, Hemant Badwaik2*, Deepa Thakur2 and Kushagra Nagori2 1
2
Ultra College of Pharmacy, Madurai (T.N) Rungta College of Pharmaceutical Sciences and Research, Bhilai (C.G) *Corresponding Author E-mail:
[email protected].
ABSTRACT:
A novel 5(4-(4-substituted)Aminobenzylidine)thiazolidine-2,4-dione derivatives were synthesized and characterized by IR and H-NMR spectral analysis. Antibacterial and antifungal activities of the compounds were assessed by in vitro growth inhibitory activity against Escherichia coli, Staphylococcus aureus, Asperigillus niger, Candida albicans by using the disc diffusion method. Most of all compounds exhibited significant antibacterial activity against Staphylococcus aureus and Escherichia coli, while weak antifungal activity against Asperigillus niger and Candida albicans.
KEYWORDS: Thiazolidine-2,4-dione, Antibacterial and antifungal activity, Disc diffusion method. INTRODUCTION:
Antibiotics are one of our most important weapons in fighting bacterial infections and have greatly benefited the health-related quality of human life since their introduction The increasing incidence of infection caused by the rapid development of bacterial resistance to most of the known antibiotics is a serious health problem1. While many factors may be responsible for mutations in microbial genomes, it has been widely demonstrated that the incorrect use of antibiotics can greatly increase the development of resistant genotypes. As multidrug-resistant bacterial strains proliferate, the necessity for effective therapy has stimulated research into the design and synthesis of novel antimicrobial molecules. Isolation, identification and application of organo-sulphur and nitrogen containing compounds resulted in their useful scientific, technical and industrial growth, which has led to the development of heterocyclic chemistry during the last two decades2-3. Vulcanization of rubber, hair curling, muscle contraction, natural aromas, vitamins, hormones, antibiotics, radio protective agents, dye stuffs, binding materials, proteins and polypeptides etc. are well known application of sulphur and nitrogen containing compounds.
Received on 21.04.2010 Accepted on 24.05.2010
Modified on 12.05.2010 © AJRC All right reserved
Asian J. Research Chem. 4(1): January 2011; Page 40-43
Thiazole are the great biological importance. This ring system occurs in thiamin (thiamine, Vit B1), the bacitracin and penicillin antibiotics (from a bacterium and a mold, respectively), Nocathiacins, a thiazole peptide class of antibiotics4. The past study shows that 2,4 thiazolidinedoine nucleus is very stable and the derivatives of 2,4 thiazolidinedoine exhibit a wide spectrum of biological activities like antidibetic, antibacterial, antifungal, antiiflamatory, anti HIV, anticouvulsants, and cardiotonic activites5-11. Thus the basis of our research programmed was centered on the introduction of benzylidine moieties at the C-5 position of the thiazolidinedione ring and screening for antimicrobial activity. Experimental Work: ANTIMICROBIAL ACTIVITY: Antibacterial and antifungal activities of the compounds were assessed by in vitro growth inhibitory activity against Escherichia coli, Staphylococcus aureus, Asperigillus niger, Candida albicans by using the disc diffusion method12-13. The compounds to be tested were dissolved in DMF to final concentrations 50 g per ml soaked in filter paper (Whatman No 4) discs of 6 mm diameter and the discs were placed on the already bacterial and fungal seeded plates and incubated at 35 ± 2°C for 48 h. Amikacin disc and ketoconazole disc were used as standard antibacterial drug and antifungal drugs. The inhibition zones were measured after subtracting inhibition due to solvent used.
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Asian J. Research Chem. 4(1): January 2011
SCHEME:
Cl
C
O
S
H COOH
+
H
H N
C
N
H
H
HCl NH
S
H
O I Reflux
CHO
Piperidine Cl O
O
NH S R
Piperidine
N H
EXPERIMENTAL:
RNH2
NH S Cl O
O
II
III
The melting points of the synthesized compounds were determined by open capillary tube method and results were uncorrected. The purity of compounds were checked by TLC using silica gel G as an adsorbent, Ethyl acetate: Butanol: CHCl3 (1:2:1) were used as mobile phase. The spot was visualized by Iodine vapour. The structures of the synthesized compounds were characterized by IR and HNMR spectral analysis in which it complies with the normal values. IR spectra’s in KBR were recorded on a FT-IR Spectrophotometer (shimadzu) and 1H-NMR spectra’s were
recorded on a bruker 300 AV TMS as an internal standard.
spectrophotometer using
2, 4 Thiazolodine dione [I]: In a 250 ml three necked flask a solution containing 56.4 gms. (0.6 mole) of chloroacetic acid in 60 ml of water and 45.6 gms (0.6 mole) of thiourea dissolved in 60 ml of water. The mixture was stirred for 15 minutes to form a white precipitate, accompanied by considerable cooling. To the contents of the flask was now added slowly 60 ml. concentrated hydrochloric acid from dropping funnel, the flask was connected with a reflux condenser and gentle heat
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Asian J. Research Chem. 4(1): January 2011
5(4-(4-amino(hydroxyphenyl))benzylidine) thiazolidine2,4-dione [IIId]. The yield 75.10%; m.p 210-211 C; IR (KBr, cm-1): 3363.80 (OH), 3149.54 (NH), 1753.17 (CO), 1608.52 and 1550.66 and 1455.56 (C=C Ar); 1H NMR (CDCl3): 4.1(s,1H ,NH), The product was filtered and washed with water to remove 5.1 (s,1H, OH ). 6.6-7.1 (m, 8H, aromatic), 7.6 (s, traces of hydrochloric acid and dried. It is re-crystallized 1H,ethylene), 8.8 (s, 1H, imide). from ethyl alcohol. The yield 85%; m.p 123-125 C; IR (KBr, cm-1): 3145.68 (N H), 1753.17 (CO); 1H NMR RESULT: (CDCl3): 3.8 (s, 2H, methylene), 8.5 (s, 1H, imide). The results indicate that most all compounds exhibited significant antibacterial activity against Staphylococcus 5( 4-chlorobenzylidine) 2, 4 thiazolidinedione [II]: aureus and Escherichia coli (Table-1, Fig-1), while weak In a 250 ml 3-necked round bottomed flask attached with a antifungal activity against Asperigillus niger and Candida dean stark apparatus, Chlorobenzaldehyde (20 gm, 0.188 albicans (Table-2, Fig-2). mole) and 2,4-thiazolidinedione (22 gm, 0.188 mole) were taken and suspended in dry toluene. To this catalytic amount of piperdine (1ml) was added. The mixture was Table1: Antibacterial activity of derivatives Zone of inhibition (in mm.) stirred and refluxed. After the complete removal of water Sr. No. Compounds E. coli S. aureus and when the temp. reached above 110 C the reaction 1 IIIa 16 14 mixture was stirred for 1 hr. On cooling the product 2 IIIb 15 12 precipitated in toluene. The compound was filtered and 3 IIIc 13 9 washed with cold dry toluene and dry ethanol. The yield 4 IIId 14 12 5 DMSO 0 0 89%; m.p 185-187 C; IR (KBr, cm-1): 3145.57 (N H), 6 AMIKACIN 18 17 1753.20 (CO), 1608.52 (C=C), 742.54 (Cl); 1H NMR (CDCl3): 6.9-7.3 (m, 4H, aromatic), 7.5 (s, 1H, ethylene), 8.5 (s, 1H, imide). applied to effect complete solution, after which the reaction mixture was stirred and refluxed for 8-10 hrs at 100-1100C. On cooling the contents of the flask solidified to a mass of clusters of white needles.
Fig.1-
5 (4-(4 substituted) Amino benzylidine) 2, 4thiazolidinedione derivatives [III]: 0.01 mole of 4-chlorobenzylidine 2, 4 thiazolidinedione (2) and substituted primary amines (0.01 mol) was refluxed in 4 ml of dry pyridine and 20 ml of acetic anhydride for 4 hrs. The excess solvent was distilled off. The mixture was cooled and poured into crushed ice. The product was filtered and recrystallized from the ethanol. 5(4-(4-amino toluene) benzylidine)thiazolidine-2,4-dione [IIIa]: The yield 65.30%; m.p 215-217°C; IR (KBr, cm-1): 3147.61 (NH), 1753.17 (CO), 1608.52 and 1550.66 and 1455.56 (C=C Ar), 2942.54 (CH aliphatic); 1H NMR (CDCl3): 2.3 (s, 3H, CH3), 4.1(s,1H ,NH),6.7-7.3 (m, 8H, aromatic), 7.5 (s, 1H,ethylene), 8.5 (s, 1H, imide). 5(4-(4-aminobenzoic acid)benzylidine) thiazolidine-2,4dione [IIIb]. The yield 71.20%; m.p 218-220°C; IR (KBr, cm-1): 3470.47 (OH), 3145.68 (NH), 1755.10 (CO), 1608.52 and 1550.66 and 1455.56 (C=C Ar); 1H NMR (CDCl3): 4.1(s,1H ,NH), Table2: Antifungal activity of derivatives 6.5-7.2 (m, 8H, aromatic), 7.6 (s, 1H,ethylene), 8.7 (s, 1H, Zone of inhibition (in mm.) Sr. imide),10.2 (s,1H, OH (carboxylic acid)). Compounds Asperigillus Candida No.
5(4-(4-amino pyridine)benzylidine) thiazolidine-2,4dione [IIIc].The yield 67.20%; m.p 227-228°C; IR (KBr, cm-1): 3149.54 (NH), 1753.17 (CO), 1608.52 and 1550.66 and 1455.56 (C=C Ar); 1H NMR (CDCl3): 4.1(s,1H ,NH), 6.5-7.2 (m, 8H, aromatic), 7.5 (s, 1H,ethylene), 8.5 (s, 1H, imide).
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1 2 3 4 6 7
IIIa IIIb IIIc IIId DMSO KETOCONAZOLE
niger 09 10 11 10 0 20
albicans 02 03 05 04 0 10
Asian J. Research Chem. 4(1): January 2011 Fig.2-
10. Michael M; New oxathiazolidinedione derivatives as potentent and selective human -3 agonist; Bioorganic and Medicinal Chemistry Letters; 2001; 11; 981-984. 11. Reddy K.A; Novel antidibetic and hypolipidemic agents 5 – hydroxyl/ben derivatives; Journal of Medicinal Chemistry 1999; 42; 3265. 12. S. Saisivam, V.B. Kishan. “Standard Method of antifungal activity”, Indian Journal of Microbiology, 2006, 46(2), p. 197. 13. Gravestock, M.B.; Ryley, J.F. Antifungal Chemotherapy. Ann. Rep. Med. Chem. 1984 19, 127.
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