Synthesis of Some 2-Thioxo-imidazolidin-4-one Derivatives and its Antimicrobial Activity

Series of newly prepared 3-{[2,6-bis(4-substituted phenyl)-1methylpiperidin-4ylidene] amino}2-thioxo-imidazolidin-4-one derivatives (3a3f) have been synthesized by the cyclization of compound (2a-2f), ethyl chloro acetate and fused sodium acetate. The chemical structures were confirmed by IR, H NMR and elemental analysis. The synthesized compounds were screened for their antimicrobial activity against four antibacterial and four antifungal organisms.

Many piperidine derivatives are found possessing pharmacological activities like anaesthetic activity 14 and antimicrobial activity 15 .2-Thioxo-imidazolindin-4-one was prepared from the reaction of aromatic aldehydes and thiosemicarbazide to give alkyl thiosemicarbazone followed by cyclization with ethyl chloroacetate in the presence of fused sodium acetate 13 .Above method was followed in the present study, thiosemicarbazide react with 2,6-diphenyl piperidin-4-one to give 2,6-disubstituted phenyl-piperidine-4thiosemicarbazone followed by cyclization with ethyl chloro acetate and fused sodium acetate.

Experimental
Melting points were recorded in open capillary tubes and are uncorrected.IR(cm -1 ) was recorded in KBr on a FT-IR shimadzu 8201 pc (4000-400 cm -1 ) and ¹H NMR and Elemental analysis (C,H,N and S) was undertaken using an Elemental analyzer model vario EL III.The purity of the compounds was checked by thin layer chromatography (TLC) with silica gel plates.

In vitro antibacterial screening
The compounds (3a-3f) were evaluated for their in vitro antibacterial activity against Staphylococcus aureus (MTCC-96), Enterococcus faecalis (MTCC-439), Escherchia coli (MTCC-739), Pseudomonas aeruginosa (MTCC-2453) by agar dilution method 18,19 was performed using Mueller -Hinton agar (Hi-Media) medium.Each compound was tested at a concentration of 100 µg/mL in DMSO.The zone of inhibition was measured after 24 h incubation at 37 ºC.Inhibition zone of the compounds clearly indicate the (3f) compound was highly active against S.aureus.The results are presented in Table 2. Inhibition of the compounds (3a-3f) were clearly observed in NO 2 substituted at benzaldehyde containing compound (3e) showed maximum antibacterial potency.Compound (3c) has nearly activity against Staphylococcus aureus, Enterococcus faecalis and compound (3d) has less activity compared with norfloxacin against all bacterial organisms.

In vitro antifungal screening
The compounds (3a-3f) were evaluated for their in vitro antifungal activity against Aspergillus niger, Candia albicans, Aspergillus fumigatus and Cryptococcus neoformans using an agar dilution method 20 with sabouraud's dextrose agar (Hi-Media).Each compound was tested at a concentration of 100 µg/mL in DMSO.The zone of inhibition was measured after incubating at 37 °C for 24 h.It was evident from screening results that only 4-OH phenyl substituted compound (3c) has remarkably enhanced the antifungal action.When compared to ketoconazole, compound (3b) is moderately active against all antifungal organisms.Compounds (3a, 3d, 3e and 3f) are less active against all antifungal organisms.All compounds are compared with ketoconazole the results are presented in Table 3.

Conclusion
The series of compound (3a-3f) 2-thioxo-imidazolidin-4-one derivatives were synthesized and screened for their antimicrobial activity.The compound (3f) has highly anti bacterial activity against S.aureus compared with norfloxacin standard and compound (3c) has highly antifungal activity aganist A. niger and A.fumigates compared with a ketoconazole standard.

Table 2 .
Antibacterial activity of the compounds (3a-3f) Zone of the inhibition measured in (mm).Indicate bacteria's are resistant to the compound 10 µg/mLNorfloxacin is used as the standard drug 100 µg/mL

Table 3 .
Antifungal activity of the compounds (3a-3f)Zone of the inhibition measured in (mm).Indicate fun gals are resistant to the compound 100 µg/mL Ketoconazole is used as the standard 100 µg/mL