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Synthesis, antimicrobial and cytotoxic activity of 2-azetidinone derivatives of pyridyl benzimidazoles

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Abstract

In the present study, a series of novel 6-(1H-benzo[d]imidazol-2-yl)-2-(3-chloro-2-oxo-4-phenylazetidin-1-yl)-4-(aryl)nicotinonitriles 6a–o were efficiently synthesized and evaluated for their in vitro antibacterial activity against Gram-positive (Staphylococcus aureus and Streptococcus pyogenes), Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacteria and fungal (Candida albicans, Aspergillus niger and Aspergillus clavatus) strains. The results of antimicrobial study revealed that compounds 6b, 6c, 6d, 6h and 6i exhibited substantial antibacterial activity while compounds 6c and 6h emerged as the most potent antifungal agents compared to the standard drugs chloramphenicol and ketoconazole, respectively. From the standpoint of SAR studies, it was observed that the presence of electron-withdrawing groups remarkably enhances the antibacterial activity of newly synthesized compounds. Further, the results of preliminary MTT cytotoxicity studies on HeLa cells suggested that potent antimicrobial activity of 6b, 6c, 6d, 6h and 6i is accompanied by low level of cytotoxic concentrations. All the newly synthesized analogues were characterized by IR, 1H NMR, 13C NMR and mass spectral data.

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Acknowledgments

Authors are thankful to the University Grants Commission, New Delhi and Department of Science & Technology, New Delhi for financial support under the NON-SAP and DST-FIST programs, respectively.

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Authors and Affiliations

  1. Division of Medicinal Chemistry, Department of Chemistry, UGC NON-SAP & DST-FIST Sponsored Department, Maharaja Krishnakumarsinhji Bhavnagar University, Mahatma Gandhi Campus, Bhavnagar, 364 002, India

    N. C. Desai, D. D. Pandya, G. M. Kotadiya & Priyanka Desai

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  1. N. C. Desai
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  2. D. D. Pandya
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  3. G. M. Kotadiya
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  4. Priyanka Desai
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Correspondence to N. C. Desai.

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Desai, N.C., Pandya, D.D., Kotadiya, G.M. et al. Synthesis, antimicrobial and cytotoxic activity of 2-azetidinone derivatives of pyridyl benzimidazoles. Med Chem Res 23, 1725–1741 (2014). https://doi.org/10.1007/s00044-013-0775-1

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  • DOI: https://doi.org/10.1007/s00044-013-0775-1

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