Synthesis, characterization and antimicrobial activity of 2-azetidinone derivatives of benzimidazoles

Some new 2-azetidinone derivatives possessing benzimidazole nucleus were synthesized and characterized by IR, NMR and mass spectral analysis. All synthesized compounds were screened for antimicrobial activity using cup plate method. All the compounds showed moderate to good antimicrobial activity and anti fungal activity


INTRODUCTION
Within the wide verity of heterocycles, benzimidazole and its derivatives are found to be most promising structures investigated in the field of pharmaceutical and medicinal chemistry. Due to the unique structural features, benzimidazole is reported to shown wide range of therapeutic activities [1][2][3]. Benzimidazole scaffold is a useful moiety for the development of molecules of pharmaceutical or biological interest [4].
The treatment of bacterial infections still remains a challenge for scientists because of factors that include rising infectious diseases and the increasing number of multidrugresistant microbial pathogens. So the discovery of novel and potent antibacterial as well as antifungal agent are the critical need of nowadays [5].

EXPERIMENTAL
All chemicals and solvents were purchased from Spectrochem Pvt Ltd., Mumbai of LR grade and were used without further purification. Melting points were taken in open capillary method and are uncorrected. IR spectra were recorded on FTIR-8400 spectrophotometer (Shimadzu, Kyoto, Japan), using DRS probe KBr pallet. 1 HNMR spectra of the synthesized compounds were recorded on a Bruker-Avance-II (400 MHz) in DMSO-d 6 solvent. Chemical shifts are expressed in δ ppm downfield from TMS as an internal standard. Mass spectra were determined using direct inlet probe on a GCMS-QP 2010 mass spectrometer (Shimadzu, Kyoto, Japan).

General procedure for the synthesis of (E)-2-(1H-benzo[d]imidazol-2-yl)-N-(4-(2benzylidene hydrazine carbonyl) aryl)benzamide 2(a-l).
A mixture of (1) (1 mmol) and substituted benzaldehyde (1 mmol) in presence of catalytic amount of acetic acid was refluxed with stirring until the reaction got complete .completion of reaction was monitored by TLC. The mixture was then cooled down and poured on to crushed ice. The solid product was filtered, dried and purified by crystallization.

ANTI MICROBIAL ACTIVITY
All the glass apparatus used were sterilized before use. The Cup plate method was used to determine the minimum inhibitory concentration (MIC) of the synthesized compounds. [17] Zone of inhibition was measured in millimetre.
Bacterial strain of Staphylococcus aureus, Bacillus megaterium, Escherichia coli, Pseudomonas fluorescens and fungal strains of Aspergillus flavus, Candida albicans were used in the present study.
DMSO was used as the control solvent for the compounds. A blank test was carried out to check the antimicrobial activity of DMSO. Ampicillin, norfloxacin and Chloramphenicol were used as the standard drugs for antibacterial activity. Greseofulvin was used as the standard drug for antifungal activity.
The synthesized 2-azetidinone 3a-3lwere screened for their antimicrobial activity by the cup plate method to evaluate the minimum inhibitory concentration Table1b.
All of the precursors 3(a-l) of the title compounds showed antibacterial activity in the range of 10-18 mm for Staphylococcus aureus, 10-17 mm for Bacillus megaterium, 10-18 mm for Escherichia coli, and 10-14 mm for Pseudomonas fluorescens.
It was observed that compound 2-chloro phenyl (3C) and 2-hydroxy phenyl (3h) against bacterial strains have found to be moderately active as compared to ampicillin.
All the compounds are not found effective as compared to Norfloxacin and Chloramphenicol.
Against fungal pathogen all compound have shown moderate activity as compared to griseofulvin.

CONCLUSION
In conclusion, a new series of compound 3(a-l) were synthesized. Synthesized compounds screened for their biological study. The investigation of antimicrobial (antibacterial and antifungal) activities data revealed that the compound 3c and 3h displayed good activity, the compound 3l showed moderate activity and rested compounds showed less activity compared with standard drugs.