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Synthesis and Antimicrobial Activity of Some 2-Alkyl-5,6-diphenylimidazo[2,1-b]thiazolidin-3-ones

Miroslav Koos*, Jan Gajdos, and Bohumil Steiner

Institute of Chemistry, Slovak Academy of Sciences, Dubravska cesta 9, SK-84238 Bratislava, Slovak Republic Phone: +421-7-378-2540; Fax: +421-7-375565; E-mail: chemmiro@savba.sk

Introduction

In our previous papers [1,2] we have reported that some nitrogen containing heterocycles with a long alkyl chain in the molecule exhibit remarkable antimicrobial efficiency, especially against gram-positive bacteria. In this respect, we have also prepared some fused heterocycles [35]. This work is an extension of our study on imidazo[2,1-b]thiazolidin-3-ones bearing an alkyl at C-2 position [5].
 

Results and Discussion

The title compounds were prepared (in about 50% yields) by intramolecular cyclization of corresponding 2-[2-(4,5-diphenylimidazolyl)thio]alkanoic acids (Scheme 1) using acetic anhydride and pyridine. The cyclic structures were confirmed on the basis of  1H and 13C NMR spectra as well as mass spectral data (intensive peaks corresponding to the molecular ions were observed).
 

 

 
 

The results of antimicrobial activity testing revealed that some of the prepared compounds 17 exhibit moderate activity against selected gram-positive bacteria (Table 1). Similarly to our previous findings [1,2], the best efficiency (expressed by the integer values of minimum inhibitory concentration - MIC) was exhibited by those derivatives where the alkyl chain R represented hexyl or octyl. Derivatives with shorter or longer alkyl chains showed considerably lower activity.
 

Table 1. Antimicrobial activity (MIC, mg.cm-3 ) of the prepared imidazo[2,1-b]thiazolidin-3-ones
 

Compound Staphyloc. 
aureus
Bacillus 
subtilis
Streptococcus 
faecalis
Escherichia 
coli
Pseudomonas 
aeruginosa
Salmonella 
typhimurium
1 1000 1000 >1000 >1000   1000   1000
2 1000 1000   1000 >1000   1000   1000
3 1000 1000   1000   1000   1000   1000
4    10  <10    100   1000 <1000 <1000
5    10    10    100   1000 <1000 <1000
6  100   100  >100   1000   1000   1000
7 1000  1000   1000   1000   1000   1000
 
 

Experimental

General procedure for the preparation of compounds 17:

A mixture of 2-[2-(4,5-diphenylimidazolyl)thio]alkanoic acid (5 mmol), acetic anhydride (2 ml) and pyridine (5 ml) was heated under reflux for 1 h. After cooling, methanol (5 ml) was carefully added and the solvents were evaporated under reduced pressure. Cold water (25 ml) was added to the residue and the product was filtered and recrystallized from ethanol to give the title compound. Yield: ~ 50%.
 

MIC determination:

MIC was determined by using the suspension method on solid cultivation media [1]. As a standard for MIC value determination we have used [1-(ethoxycarbonyl)-pentadecyl]-trimethylammonium bromide (Septonex), a commercial antiseptic agent.
 

Acknowledgment

Financial support of this research by the Scientific Grant Agency (VEGA, Slovak Academy of Sciences and Ministry of Education, Bratislava, Project No. 4144) is gratefully appreciated.
 

References

1. Koos, M.; Steiner, B.; Repas, M. Chem. Papers 1991, 45, 279.
2. Koos, M.; Zvakova, A.; Steiner, B.; Matulova, M. Chem. Papers 1992, 46, 50.
3. Steiner, B.; Koos, M.; Matulova, M.; Proksa, B. Monatsh. Chem. 1993, 124, 425.
4. Koos, M. Chem. Papers 1994, 48, 108.
5. Koos, M. Monatsh. Chem. 1994, 125, 1011.