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

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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, 1 H NMR, 13 C 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.

Original languageEnglish
Pages (from-to)329-339
Number of pages11
JournalMedicinal Chemistry Research
Volume28
Issue number3
DOIs
Publication statusPublished - Mar 15 2019

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Keywords

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

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry

Cite this

Borazjani, N., Jarrahpour, A., Rad, J. A., Mohkam, M., Behzadi, M., Ghasemi, Y., Mirzaeinia, S., Karbalaei-Heidari, H. R., Ghanbari, M. M., Batta, G., & Turos, E. (2019). Design, synthesis and biological evaluation of some novel diastereoselective β-lactams bearing 2-mercaptobenzothiazole and benzoquinoline. Medicinal Chemistry Research, 28(3), 329-339. https://doi.org/10.1007/s00044-018-02287-0