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Design, synthesis and biological evaluation of some novel diastereoselective β-lactams bearing 2-mercaptobenzothiazole and benzoquinoline

  • Nassim Borazjani
  • Aliasghar Jarrahpour
  • Javad Ameri Rad
  • Milad Mohkam
  • Maryam Behzadi
  • Younes Ghasemi
  • Somayyeh Mirzaeinia
  • Hamid Reza Karbalaei-Heidari
  • Mohammad Mehdi Ghanbari
  • Gyula Batta
  • Edward Turos
Original Research
  • 13 Downloads

Abstract

We report the synthesis of some novel β-lactam hybrids of 2-mercaptobenzothiazole and benzoquinoline. These compounds were synthesized by a [2 + 2]-cycloaddition reaction of imines 8a-d and ketenes derived from substituted acetic acids. The reaction was totally diastereoselective leading exclusively to the formation of cis-β-lactams 10a-m. All products were obtained in good to excellent yields and their structures were established based on IR, 1H NMR, 13C NMR spectral data and elemental analysis. Schiff bases 8a-d and β-lactam hybrids 10a-m were evaluated for antimicrobial activities against six bacterial species. The minimum inhibitory concentration (MIC) values indicate that two of the β-lactams, 10k and 10m, have good activities against the two Gram-negative bacteria, E. coli and P. aeruginosa, while three of the Schiff bases, 8a-c, are active against P. aeruginosa and the Gram-positive pathogen S. aureus. The molecular and cellular basis for these observed antibacterial properties are not determined. Moreover, the five most active compounds showed acceptably low cytotoxicity (less than 25% cell growth inhibition after 72 h of incubation) against the MCF-7 cell line, and below 10% in vitro hemolytic activity at 50 and 200 µM concentrations. These results suggest a need for further inquiry into the reason for why these compounds are bioactive, and as to what their full biological activities and antibiotic potential may be. The cis stereochemistry of β-lactam 10a was confirmed by X-ray crystallographic studies.

Keywords

β-Lactam Hybrid 2-Mercaptobenzothiazole Benzoquinoline Antimicrobial Hemolysis Mammalian cell toxicity 

Notes

Acknowledgements

The authors would like to thank the Shiraz University Research Council for financial support (Grant No. 97-GR-SC-23) and Dr. Attila Benyei for collecting X-ray data.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

44_2018_2287_MOESM1_ESM.docx (1.5 mb)
Supporting information

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Nassim Borazjani
    • 1
  • Aliasghar Jarrahpour
    • 1
  • Javad Ameri Rad
    • 1
  • Milad Mohkam
    • 2
  • Maryam Behzadi
    • 2
  • Younes Ghasemi
    • 3
    • 4
  • Somayyeh Mirzaeinia
    • 5
  • Hamid Reza Karbalaei-Heidari
    • 5
  • Mohammad Mehdi Ghanbari
    • 6
  • Gyula Batta
    • 6
  • Edward Turos
    • 7
  1. 1.Department of Chemistry, College of SciencesShiraz UniversityShirazIran
  2. 2.Biotechnology Research CenterShiraz University of Medical SciencesShirazIran
  3. 3.Pharmaceutical Research CenterShiraz University of Medical SciencesShirazIran
  4. 4.Department of Biotechnology, School of PharmacyShiraz University of Medical SciencesShirazIran
  5. 5.Molecular Biotechnology Lab., Department of Biology, Faculty of SciencesShiraz UniversityShirazIran
  6. 6.Department of ChemistryUniversity of DebrecenDebrecenHungary
  7. 7.Center for Molecular Diversity in Drug Design, Discovery, and Delivery, Department of ChemistryUniversity of South FloridaTampaUSA

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