Int J Curr Pharm Res, Vol 7, Issue 3, 92-94Original Article


SYNTHETIC AND ANTIMICROBIAL ACTIVITY OF 4 THIAZOLIDINONES

RENU DIXIT, A. K. HALVE, C. P. SHINDE, PRADEEP K. SONI

School of Studies in Chemistry, Jiwaji University, Gwalior 474001, Madhya Pradesh, India
Email: drenu23@gmail.com

Received: 08 May 2015, Revised and Accepted: 07 Jun 2015

ABSTRACT

Objective: Thiazolidinone, a saturated form of thiazole with carbonyl group on the fourth carbon, has been considered as magic moieties (Wonder nucleus) which possess almost all types of biological activities. This diversity in the biological response profile has attracted the attention of many researchers to explore this skeleton to its multiple potential against several activities

Methods: Looking to the importance of N and S hetero cycles in the medical field, 4-thiazolidinone derivatives (3b,4b) have been synthesized by cyclization of substituted imines(1a,2a) with mercaptoacetic acid in presence of anhydrous ZnCl2 as a catalyst in DMF. The 4-thiazolidinone derivatives have also been tested against two bacterial strains viz. S. aureus and E. coli and two fungal pathogens viz. A. niger and C. albicans using Kirby-Bauer method.

Result: New series of azomethines and 4 thiazolidinones compounds have been prepared. The synthesized compounds were characterized on the basis of IR, 1H-NMR, and elemental analysis. The purity of the compounds was checked using pre coated TLC plates (MERCK) using n-hexane: ethyl acetate (8:2) solvent system. The synthesized compounds show good antimicrobial acivity.

Conclusion: The zone of inhibition is directly proportional to the degree of sensitivity of the bacterial, fungal strain and concentration of compound under test. A systematic perusal data of antimicrobial activity reveals that, with the increase in concentration of drug, increase in zone of inhibition occur in petridish. Better antimicrobial activity have been pointed out in synthesized compounds

Keywords: Schiff bases, 4-thiazolidinones, Antibacterial activity, Antifungal activity etc.

INTRODUCTION

An antimicrobial is a substance that kills or inhibits the growth of microorganisms such as bacteria, fungi, or protozoans. Antimicrobial drugs either kill microbes (microbicidal) or prevent the growth of microbes (microbistatic). The history of antimicrobials begins with the observations of Pasteur and Joubert, who discovered that one type of bacteria could prevent the growth of another. They did not know at that time that the reason one bacterium failed to grow was that the other bacterium was producing an antibiotic. Technically, antibiotics are only those substances that are produced by one microorganism that kill, or prevent the growth, of another microorganism. Of course, in today's common usage, the term antibiotic is used to refer to almost any drug that attempts to rid your body of a bacterial infection. Antimicrobials include not just antibiotics, but synthetically formed compounds as well. Schiff bases are the important compound owing their wide range of biological activities and industrial application. They have been found to possess the pharmacological activities such as anticancer [1] antibacterial [2-7] antifungal [8-9], antitubercular [10], antiinflammetery [11,12], antimicrobial [13-16] and antiviral [17], antioxidant [18] etc.

They also serve as a backbone for the synthesis of various heterocyclic compounds. The presence of azomethine functional group is responsible for antimicrobial activitiy, which can be altered depending upon the type of substituent present on 4-thiazolidinones have been shown to have various important biological activities [19-21]. Some of these compounds were screened for their antibacterial and antitubercular static activities, and it has been found that some of them have moderate to good biological properties [22]. The biological significance of this class of compounds impelled us to continue working on the synthesis of new thiazolidinone derivatives.

MATERIALS AND METHODS

(A) Synthesis of 3-methoxy 4–acetyloxy benzaldehyde

The vanillin (5.3 gm; 0.970 M) was dissolved in aqueous sodium hydroxide solution (25 mL, 2.5N) and crushed ice (50 gm) along with acetic anhydride (5.7 ml) was added. The contents were vigorously stirred, for one hour. The solid were filtered washed successively with sodium hydroxide solution (0.1N, 20 ml) and water (20 ml). The product was recrystallised from petroleum ether or ethanol, white shining crystals were obtained.

(B) Synthesis of Schiff Bases of 2 methoxy-4-[N-(4 substituted) carboximidoyl] phenol

3–methoxy 4–acetyloxybenzyldehyde (0.005 M) were dissolved in absolute ethanol and the contents were refluxed for 5 hrs. The reaction mixture was cooled in ice water and acidified with a drop of sulphuric acid. It was filtered under suction washed with ethanol and recrystallised from aq, ethyl alcohol, when white crystals of the schiff base were obtained.

(C) Synthesis of 2–[(4–substituted phenyl)–2–(4–methylphenyl) ]–1, 2–thizolidin–4–one

In a round bottom flask schiff base (0.001 M), in dimethyl formamide was mixed with mercaptoacetic acid (0.001 M, in DMF) with continous stirring. A pinch of anhydrous ZnCl2 was added followed by refluxing for 16 hrs. The resction mixture was then allowed to cooled and poured over crushed ice. The solid thus obtained was filtered, washed and recrystallized with aq. glacial acetic acid.

1apale yellow solid, 72%, mp 121oC IR(KBr cm-1): 3000 cm-1 (C=H stretch), 1725 cm-1 (C=O stretch), 1601 cm-1 (C=NH stretch), 758 cm-1 (C-Cl stretch) 1HNMR: δ 8.7 (S, 1H,-CH=N), δ 7.6 (t, 2H, Ar-H), δ 7.8-δ 7.9 (d, 1H, Ar-H), δ 3.4 (S,1H, OCH3)

2a white solid, 84%, mp 130oC IR (KBR cm-1): 1700 cm-1 (C=O stretch), 1623 cm-1 (C=N stretch), 3000 cm-1 (C-H stretch) 1HNMR: δ 8.7 (s, 1H, CH=N), δ 7.6 (t, 2h, Ar-H), δ 2.4 (s, 3H, CH3)

3b Light Brown, 69%, mp 190oC IR (KBR cm-1): 3460 cm-1 (N-H stretch), 1690 cm-1(C=Ostretch) 1HNMR: δ 8.5 (S, 1H,CH-N). δ6.9-7.4 (m, 4H, Ar-H), δ 5.7 (s, 1H, CH2), δ 3.4 (s, 1H, OCH3), δ 2.4 (s, 1H, CH3)

4b Light Brown, 78%, mp 169oCIR (KBR cm-1): 3350 cm-1 (N-H stretch), 1690 cm-1(C=Ostretch) 1HNMR: δ 8.5 (S, 1H,CH-N). δ6.9-7.4 (m, 4H, Ar-H), δ 5.7 (s, 1H, CH2), δ 3.4 (s, 1H, OCH3), δ 2.4 (s, 1H, CH3), δ 3.9 (s, 1H, SCH)

Antimicrobial studies

The 5–membered compounds are evaluated for antimicrobial activity against the two bacterial strains viz. S. aureus and E. coli and two fungal pathogens viz. A. niger and C. albicans using the disc diffusion method. Results obtained were compared with that of standard drug Chloramphenicol and Clotrimazole for antibacterial and antifungal activity respectively

Disc diffusion assay

Using Kirby-Bauer method to determine the antibacterial susceptibility of a compound at fixed concentration doses. For this, few colonies of organisms were inoculated in 2–5 ml broth and grown for2.5 hours. The agar plates were dried for 30 minutes before inoculation, to prevent flow of inoculated material during incubation. A sterile cotton swab is dipped into the bacterial suspension and used to spread evenly the dilute culture on the agar surface. The disc (5 mm diameter were made up of Whatman filter paper No. 1) was autoclaved and then dried at 60oC for one hour. The sterile filter paper discs, impregnated with fixed doses viz 400 µg (10 ml) and 800 µg (10 ml) of compound were placed on the pre-inoculated surface by flamed forceps. The disc bearing plates were incubated within 30 minutes at 37oC for 24 hours. After incubation, the inhibition zone diameter was measured. The zone of inhibition is directly proportional to the degree of sensitivity of the bacterial, fungal strain and concentration of compound under test. A systematic perusal data of antimicrobial activity reveals that. With the increase in concentration of drug, increase in the zone of inhibition occurs in petridish.

RESULTS AND DISCUSSION

Evaluation of antimicrobial activity of Schiff bases and thiazolidinones

Two compounds of schiff bases and two compounds of 4-thiazolidinones were screened against selected strains of bacteria viz S. aureus, E. coli and fungal A. niger, C. albicans using disc diffusion assay.

The zone of inhibition around the disc against the test bacteria and fungus was determined at 400 µg and 800 µg (10 ml) concentration by disc diffusion assay as indicative of the antibacterial and antifungal activity.

Table 1: Antimicrobial studies of Schiff bases and 4-thiazolidinones compounds

S. No. Compound Diameter of zone of inhibition in mm
Bacteria Fungi
S. aureus E. coli A. niger C. albicans
400 µg/disc 800 µg/disc 400 µg/disc 800 µg/disc 400 µg/disc 800 µg/disc 400 µg/disc 800 µg/disc
1 1a - 05 09 14 09 12 11 13
2 2a 06 09 10 12 06 09 10 12
3 3b 09 11 04 13 06 11 05 09
4 4b - 06 04 14 11 16 10 14
5 Chloramphenicol 16 22 12 26 - - - -
6 Clotrimazole - - - - 22 30 16 20

R= CH3, Cl

CONCLUSION

The result study reports the successful synthesis and antimicrobial activity of new imines and 4-thiazolidinone derivatives. The antimicrobial activity revealed that all the compounds have good antibacterial and antifungal activity which may be due to the presence of azomethine linkage in imines and NandS containing 5 membered compounds.

ACKNOWLEDGEMENT

The authors are grateful to Prof and Head S. K. Shrivastava, School of studies in Chemistry Jiwaji University, for providing necessary facilities to carry out this work.

CONFLICT OF INTERESTS

Declared None

REFERENCES

  1. Jesmin M, Ali MM, Khanam JA. Thai, Pesticidal activities of some Schiff bases derived from benzoin, salicylaldehyde, aminophenol and 2,4 dinitrophenyl hydrazine. J Pharm Sci 2010;34:20-31.
  2. Gangadasu B, Narender P, Raju BC, Rao VJ. Base induced Carbon–Nitrogen (C=N) double bond migration in schiff bases. Indian J Chem 2005;44(B):2598-600.
  3. Parekh J, Inamdhar P, Nair R, Baluja S, Chandra S. Synthesis and antimicrobial activities of some novel schiff bases of 5 substituted isatin derivatives. J Serb Chem Soc 2005;70:1155-61.
  4. Devi TP, Singh RKH. Complexes of nickel II with the schif bases derived from condensation of Salicylaldehyde and Bis-Ni(AMUH)2Cl2. Rasayan J Chem 2010;3:266-70.
  5. Nair R, Shah A, Baluja S, Chandra S. Synthesis 7 antibacterial activities of some schiff base complex. J Serb Chem Soc 2006;71:733-44.
  6. Iqbal A, Siddiqui HL, Ashraf CM, Ahmad M, Weaver GW. Synthesis, Characterization and antibacterial activities of azomethine derivatives derived from 2-Formylphenoxyacetic acid. Molecules 2007;12:245-25.
  7. Khan J, Rehman W, Muhammad B, Danish Muhammad, Mahmood Q, Bukhari N. Biologically active organotin IV complexes of schiff bases derived from indoline 2,3 dione and 2 amino benzoic acid. World Appl Sci J 2009;6:1563-8.
  8. Jamila K, Wajid R, Bakhtiar M, Danish M. Biologically active organotin IV schiff bases complex. J Iran Chem Soc 2010;7:495-9.
  9. Prakas CR, Raja Selvam TP, Saravanam G, Karthick V, Kumar PD. Synthesis and antimicrobial activities of some novel schiff bases of 5 substituted Isatin derivatives. Rasayan J Chem 2009;2:960-8.
  10. Ferreira MDL, Vasconcelos TRA, Carvalho EMD, Lourenco MCS, Wardell JL, Ferreira VF, et al. Synthesis and antitubercular activity of novel schiff bases derived from D-Mannitol. Carbohydr Res 2009;344:2042-7.
  11. Sondhi SM, Kinodia M, Jain S, Kumar A. Synthesis of biologically active novel bis schiff bases, Bis hydrazine and bis gunidine derivatives. Indian J Chem 2009;48(B):1128-36.
  12. Vazzana I, Terranova E, Mattioli F, Sparatore F. Aromatic schiff bases and 2,3 disubstituted 1,3 thiazolidin-4-one derivatives as antiinflammotory agents. ARKIVOC 2004;5:364-74.
  13. Bairagi S, Bhosale A, Deodhar Meenakshi N. Design, Synthesis and evaluation of schiff bases of 4 chloro 3 coumarin aldehyde as antimicrobial agents. E J Chem 2009;6:759-62.
  14. Kumar S, Dhar DN, Saxena PN. Synthesis, Characterization and antimicrobial properties of schiff bases derived from condensation of 8-formyl 7-hydroxy-4-methyl coumarin and substituted triazole derivatives. J Sci Ind Res 2009;68:181-7.
  15. Ravichandran V, Mohan S, Kumar KS. Synthesis and antimicrobial activity of mannich bases of isatin and its derivatives with2-[(2,6 dichlorophenyl)amino] phenyl acetic acid. ARKIVOC 2007;14:51-7.
  16. Satyanarayana VSV, Sreevani P, Sivakumar A, Vijayakumar V. Synthesis and antimicrobial activity ofnew schiff bases containing coumarinmoeity and their spectral characterization. ARKIVOC 2008;17:221-33.
  17. Jarrahpour A, Khalili D. Synthesis, Antibacterial, Antifungal and antiviral activity evaluation. Molecules 2006;11:59-63.
  18. Valentina P, Ilango K, Deepthi M, Harusha P, Pavani G, Sindhura KL, et al. Antioxidant activity of some substituted 1,2,4–triazo-5-thion schiff bases. J Pharm Sci Res 2009;1:74-7.
  19. Ocal N, Yolacan C, Kaban S, Leonor Y, Vargas M, Kouznetsov VJ. Transformations of schiff bases derived from quinoline-8-carbaldehyde. Synthesis of C-8 sunbstituted quinoline. Heterocycl Chem 2001;38:233-6.
  20. Aydogan F, Ocal N, Turgut Z, Yolacan C. Transformations of aldimines derived from pyrrole-2-carbaldehyde. synthesis of thiazolidino fused complexes. Bull Korean Chem Soc 2001;22:476-80.
  21. Ocal N, Aydogan F, Yolacan C, Turgut Z. Synthesis of some furo-thiazolidine derivatives starting from aldimines. J Heterocycl Chem 2003;40:721-4.
  22. Barbuliene MM, Sakociute V, Vainilavicius P. Synthesis and characterization of new pyrimidine-based 1,3,4–oxa (thia) diazoles, 1,2,4–triazoles and 4-thiazolidinones. ARKIVOC 2009;12:281-9.