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Medicinal Chemistry Research

, Volume 28, Issue 3, pp 329–339 | Cite as

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

  • Nassim Borazjani
  • Aliasghar JarrahpourEmail author
  • Javad Ameri Rad
  • Milad Mohkam
  • Maryam Behzadi
  • Younes Ghasemi
  • Somayyeh Mirzaeinia
  • Hamid Reza Karbalaei-Heidari
  • Mohammad Mehdi Ghanbari
  • Gyula Batta
  • Edward Turos
Original Research
  • 106 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

References

  1. Ahmed A, Daneshtalab M (2012) Polycyclic quinolones (part 1) thieno [2, 3-b] benzo [h] quinoline derivatives: design, synthesis, preliminary in vitro and in silico studies. Heterocycles 85:103–122CrossRefGoogle Scholar
  2. Afzal O, Kumar S, Haider MR, Ali MR, Kumar R, Jaggi M, Bawa S (2015) A review on anticancer potential of bioactive heterocycle quinoline. Eur J Med Chem 97:871–910CrossRefPubMedGoogle Scholar
  3. Alborz M, Jarrahpour A, Pournejati R, Karbalaei-Heidari HR, Sinou V, Latour C, Brunel JM, Sharghi H, Aberi M, Turos E (2018) Synthesis and biological evaluation of some novel diastereoselective benzothiazole β-lactam conjugates. Eur J Med Chem 143:283–291CrossRefPubMedGoogle Scholar
  4. Alcaide B, Almendros P, Aragoncillo C (2007) β-Lactams: versatile building blocks for the stereoselective synthesis of non-β-lactam products. Chem Rev 107:4437–4492CrossRefPubMedGoogle Scholar
  5. Baluja SH, Chanda S (2017) Synthesis and antimicrobial screening of some novel chloroquinolines in DMF and DMSO. Int J Bioorg Chem 2:118–124Google Scholar
  6. Bandyopadhyay D, Cruz J, Banik BK (2012) Novel synthesis of 3-pyrrole substituted β-lactams via microwave-induced bismuth nitrate-catalyzed reaction. Tetrahedron 68:10686–10695CrossRefGoogle Scholar
  7. Bawa S, Kumar S, Drabu S, Kumar R (2010) Structural modifications of quinoline-based antimalarial agents: Recent developments. J Pharm Bioallied Sci 2:64–71CrossRefPubMedPubMedCentralGoogle Scholar
  8. Bhat I, Mishra SK, James J, Shastry C (2011) Antimicrobial studies of synthesized azetidinone derivatives from sulfamethoxazole moiety. J Chem Pharm Res 3:114–118Google Scholar
  9. Bhati SK, Kumar A (2008) Synthesis of new substituted azetidinoyl and thiazolidinoyl-1, 3, 4-thiadiazino (6,5-b) indoles as promising anti-inflammatory agents. Eur J Med Chem 43:2323–2330CrossRefPubMedGoogle Scholar
  10. Çelik I, Akkurt M, Jarrahpour A, Ameri Rad J, Çelik O (2015) Crystal structure of 2-[(3S,4S)-4-(anthracen-9-yl)-1-(4-methoxyphenyl)-2-oxoazetidin-3-yl]-2-aza-2H-phenalene-1,3-dione unknown solvate Acta Crystallogr Sect E Struct Rep 71:o184–o185CrossRefGoogle Scholar
  11. Cerić H, Šindler-Kulyk M, Kovačević M, Perić M, Živković A (2010) Azetidinone-isothiazolidinones: Stereoselective synthesis and antibacterial evaluation of new monocyclic β-lactams. Bioorg Med Chem 18:3053–3058CrossRefPubMedGoogle Scholar
  12. Chavan AA, Pai NR (2007) Synthesis and biological activity of N-substituted-3-chloro-2-azetidinones. Molecules 12:2467–2477CrossRefPubMedPubMedCentralGoogle Scholar
  13. Cressier D, Prouillac C, Hernandez P, Amourette C, Diserbo M, Lion C, Rima G (2009) Synthesis, antioxidant properties and radioprotective effects of new benzothiazoles and thiadiazoles. Bioorg Med Chem 17:5275–5284CrossRefPubMedGoogle Scholar
  14. D’hooghe M, Dekeukeleire S, Leemans E, De Kimpe N (2010) Use of functionalized β-lactams as building blocks in heterocyclic chemistry. Pure Appl Chem 82:1749–1759CrossRefGoogle Scholar
  15. El-Gamal K, Sherbiny F, El-Morsi A, Abu-El-khair H, Eissa I, El-Sebaei M (2015) Design, synthesis and antimicrobial evaluation of some novel quinoline derivatives. Pharm Pharmacol Int J 2:00036Google Scholar
  16. Galletti P, Giacomini D (2011) Monocyclic β-lactams: new structures for new biological activities. Curr Med Chem 18:4265–4283CrossRefPubMedGoogle Scholar
  17. Herrera Cano N, Ballari MS, Lopez AG, Santiago AN (2015) New synthesis and biological evaluation of benzothiazole derivates as antifungal agents. J Agric Food Chem 63:3681–3686CrossRefPubMedGoogle Scholar
  18. Hosseyni S, Jarrahpour A (2018) Org Bimol Chem.  https://doi.org/10.1039/C8OB01833B.
  19. Huang W, Yang GF (2006) Microwave-assisted, one-pot syntheses and fungicidal activity of polyfluorinated 2-benzylthiobenzothiazoles. Bioorg Med Chem 14:8280–8285CrossRefPubMedGoogle Scholar
  20. Indrani B, Fredrick FB, Bimal KB (2017) Microwave-induced synthesis of enantiopure β-lactams. Mod Chem Appl 5:2329–6798Google Scholar
  21. Islami MR, Allen AD, Vukovic S, Tidwell TT (2010) N-pyrrolylketene: a nonconjugated heteroarylketene. Org Lett 13:494–497CrossRefPubMedGoogle Scholar
  22. Jarrahpour A, Zarei M (2006) Synthesis of novel N-sulfonyl monocyclic β-lactams as potential antibacterial agents. Molecules 11:49–58CrossRefPubMedPubMedCentralGoogle Scholar
  23. Jarrahpour A, Rezaei S, Sinou V, Latour C, Brunel JM (2017) Synthesis of some novel 3-spiro monocyclic b-lactams and their antibacterial and antifungal investigations. Iran J Sci Technol Trans A Sci 41:337–342CrossRefGoogle Scholar
  24. Kamath A, Ojima I (2012) Advances in the chemistry of β-lactam and its medicinal applications. Tetrahedron 68:10640–10664CrossRefPubMedPubMedCentralGoogle Scholar
  25. Kumar S, Bawa S, Gupta H (2009) Biological activities of quinoline derivatives. Mini Rev Med Chem 9:1648–1654CrossRefPubMedGoogle Scholar
  26. Letavic MA, Bronk BS, Bertsche CD, Casavant JM, Cheng H, Daniel KL, George DM, Hayashi SF, Kamicker BJ, Kolosko NL (2002) Synthesis and activity of a novel class of tribasic macrocyclic antibiotics: the triamilides. Bioorg Med Chem Lett 12:2771–2774CrossRefPubMedGoogle Scholar
  27. Ling LL, Schneider T, Peoples AJ, Spoering AL, Engels I, Conlon BP, Mueller A, Schäberle TF, Hughes DE, Epstein S (2015) A new antibiotic kills pathogens without detectable resistance. Nature 517:455–459CrossRefPubMedGoogle Scholar
  28. Meunier B (2007) Hybrid molecules with a dual mode of action: dream or reality? Acc Chem Res 41:69–77CrossRefPubMedGoogle Scholar
  29. Mishra RK, Coates CM, Revell KD, Turos E (2007) Synthesis of 2-oxazolidinones from β-lactams: Stereospecific total synthesis of (−)-cytoxazone and all of its stereoisomers. Org Lett 9:575–578CrossRefPubMedGoogle Scholar
  30. Morphy R, Rankovic Z (2006) The physicochemical challenges of designing multiple ligands. J Med Chem 49:4961–4970CrossRefPubMedGoogle Scholar
  31. Nagarajan S, Arjun P, Raaman N, Shah A, Sobhia ME, Das TM (2012) Stereoselective synthesis of sugar-based β-lactam derivatives: docking studies and its biological evaluation. Tetrahedron 68:3037–3045CrossRefGoogle Scholar
  32. Piens N, De Kimpe N, D'hooghe M (2016) Recent progress in the use of functionalized á-lactams as building blocks in heterocyclic chemistry. progress in heterocyclic chemistry 28:27–55Google Scholar
  33. Raj R, Sharma V, Hopper MJ, Patel N, Hall D, Wrischnik LA, Land KM, Kumar V (2014) Synthesis and preliminary in vitro activity of mono-and bis-1H-1, 2, 3-triazole-tethered β-lactam–isatin conjugates against the human protozoal pathogen Trichomonas vaginalis. Med Chem Res 23:3671–3680CrossRefGoogle Scholar
  34. Rajamäki SH, De Luca L, Capitta F, Porcheddu A (2016) A telescopic one-pot synthesis of β-lactam rings using amines as a convenient source of imines. RSC Adv 6:38553–38557CrossRefGoogle Scholar
  35. Ramachandran E, Thomas SP, Poornima P, Kalaivani P, Prabhakaran R, Padma VV, Natarajan K (2012) Evaluation of DNA binding, antioxidant and cytotoxic activity of mononuclear Co (III) complexes of 2-oxo-1, 2-dihydrobenzo[h]quinoline-3-carbaldehyde thiosemicarbazones. Eur J Med Chem 50:405–415CrossRefPubMedGoogle Scholar
  36. Riss TL, Moravec RA, Niles AL, Benink HA, Worzella TJ, Minor L (2013) Cell viability assays, assay guidance manual. Eli Lilly & Company and the National Center for Advancing Translational Sciences, Bethesda, MD, p 1–23Google Scholar
  37. Salunkhe D, Piste P (2014) A brief review on recent synthesis of 2-azetidinone derivatives. Int J Pharm Life Sci 5:666–689Google Scholar
  38. Shipra H, Baluja H, Kajal H (2015) Biological activities of some novel quinoline derivatives. Int J Basic Appl Chem Sci 5:45–60. InternationalGoogle Scholar
  39. Srivastava A, Singh R (2005) Vilsmeier-Haack reagent: a facile synthesis of 2-chloro-3-formylquinolines from N-arylacetamides and transformation into different functionalities. Indian J Chem 44:1868–1875Google Scholar
  40. Vandekerckhove S, D’hooghe M (2013) Exploration of aziridine-and β-lactam-based hybrids as both bioactive substances and synthetic intermediates in medicinal chemistry. Bioorg Med Chem 21:3643–3647CrossRefPubMedGoogle Scholar
  41. Wang F, Cai S, Wang Z, Xi C (2011) Synthesis of 2-mercaptobenzothiazoles via DBU-promoted tandem reaction of o-haloanilines and carbon disulfide. Org Lett 13:3202–3205CrossRefPubMedGoogle Scholar
  42. Westrip SP (2010) Document origin: publCIF. J Apply Cryst 43:920–925CrossRefGoogle Scholar
  43. Zhilitskaya LV, Yarosh NO, Shagun LG, Dorofeev IA, Larina LI (2017) Siloxane derivatives of 2-mercaptobenzothiazole. Mendeleev Commun 27:352–354CrossRefGoogle Scholar
  44. Zhong W, Ma W, Liu Y (2011) First construction of 12H-thiochromeno [2,3-b] quinolines and 5H-benzo [7,8] thiocino-[2,3-b] quinolines via intramolecular Friedel–Crafts reaction of Morita–Baylis–Hillman adducts. Tetrahedron 67:3509–3518CrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  • Nassim Borazjani
    • 1
  • Aliasghar Jarrahpour
    • 1
    Email author
  • 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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