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, G. Batta, Edward Turos

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish
JournalMedicinal Chemistry Research
DOIs
Publication statusAccepted/In press - Jan 1 2019

Fingerprint

Bearings (structural)
Lactams
Schiff Bases
Nuclear magnetic resonance
Stereochemistry
Imines
Cycloaddition
MCF-7 Cells
Cycloaddition Reaction
Cell growth
Microbial Sensitivity Tests
Pathogens
Cytotoxicity
Bioactivity
Gram-Negative Bacteria
Escherichia coli
Bacteria
Acetates
Cells
X-Rays

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

Design, synthesis and biological evaluation of some novel diastereoselective β-lactams bearing 2-mercaptobenzothiazole and benzoquinoline. / Borazjani, Nassim; Jarrahpour, Aliasghar; Rad, Javad Ameri; Mohkam, Milad; Behzadi, Maryam; Ghasemi, Younes; Mirzaeinia, Somayyeh; Karbalaei-Heidari, Hamid Reza; Ghanbari, Mohammad Mehdi; Batta, G.; Turos, Edward.

In: Medicinal Chemistry Research, 01.01.2019.

Research output: Contribution to journalArticle

Borazjani, N, Jarrahpour, A, Rad, JA, Mohkam, M, Behzadi, M, Ghasemi, Y, Mirzaeinia, S, Karbalaei-Heidari, HR, Ghanbari, MM, Batta, G & Turos, E 2019, 'Design, synthesis and biological evaluation of some novel diastereoselective β-lactams bearing 2-mercaptobenzothiazole and benzoquinoline', Medicinal Chemistry Research. https://doi.org/10.1007/s00044-018-02287-0
Borazjani, Nassim ; Jarrahpour, Aliasghar ; Rad, Javad Ameri ; Mohkam, Milad ; Behzadi, Maryam ; Ghasemi, Younes ; Mirzaeinia, Somayyeh ; Karbalaei-Heidari, Hamid Reza ; Ghanbari, Mohammad Mehdi ; Batta, G. ; Turos, Edward. / Design, synthesis and biological evaluation of some novel diastereoselective β-lactams bearing 2-mercaptobenzothiazole and benzoquinoline. In: Medicinal Chemistry Research. 2019.
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AU - Borazjani, Nassim

AU - Jarrahpour, Aliasghar

AU - Rad, Javad Ameri

AU - Mohkam, Milad

AU - Behzadi, Maryam

AU - Ghasemi, Younes

AU - Mirzaeinia, Somayyeh

AU - Karbalaei-Heidari, Hamid Reza

AU - Ghanbari, Mohammad Mehdi

AU - Batta, G.

AU - Turos, Edward

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N2 - 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.

AB - 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.

KW - 2-Mercaptobenzothiazole

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KW - Mammalian cell toxicity

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