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Synthesis and antimicrobial/antimalarial activities of novel naphthalimido trans-β-lactam derivatives

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Abstract

This paper describes for the first time the synthesis and microbiological assessment of some new β-lactam derivatives containing a 1,8-naphthalimide functional group. These compounds were obtained through a [2 + 2] cyclocondensation (Staudinger reaction) of a ketene derived from 2-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl) acetic acid (Alrestatin) and various N-arylimines. The reaction was totally diastereoselective leading exclusively to the formation of trans-β-lactam adducts 3a–l, which were characterized by FT-Infra Red, 1H NMR, 13C NMR, mass spectrometry, elemental analyses, and X-ray crystallography, and then individually evaluated for antibacterial and antimalarial activities. Two of the β-lactams, 3c and 3l, afforded IC50 values of 3 and 5 µM, respectively, against Plasmodium falciparum K1 resistant strain.

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Acknowledgements

The authors would like to thank the Shiraz University Research Council for financial support (Grant No. 95-GR-SC-23). T.B.H. and Y.N.M. extend their sincere appreciation to the Deanship of Scientific Research at King Saud University for funding this Prolific Research Group (PRG-1437-29).

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Authors and Affiliations

  1. Department of Chemistry, College of Sciences, Shiraz University, Shiraz, 71946-84795, Iran

    Javad Ameri Rad & Aliasghar Jarrahpour

  2. Aix-Marseille Université, UMR-MD3 Relation hôte-parasites, Physiopathologie & Pharmacologie, Faculté de pharmacie, Bd Jean Moulin, F-13385, Marseille, France

    Christine Latour & Veronique Sinou

  3. Centre de Recherche en Cancérologie de Marseille (CRCM), CNRS, UMR7258, Institut Paoli Calmettes, Aix-Marseille Université, UM 105, Inserm, U1068, Faculté de Pharmacie, Bd Jean Moulin, F-13385, Marseille, France

    Jean Michel Brunel

  4. Ibn Zohr University, Polydisciplinary Faculty, 45000, Ouarzazate, Morocco

    Hsaine Zgou

  5. Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia

    Yahia Mabkhot

  6. LCM Laboratory, FSO, University of Mohammed Premier, Faculty of Sciences, 60000, Oujda, Morocco

    Taibi Ben Hadda

  7. Center for Molecular Diversity in Drug Design, Discovery, and Delivery, Department of Chemistry, University of South Florida, CHE 205, 4202 East Fowler Avenue, Tampa, FL, 33620, USA

    Edward Turos

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  1. Javad Ameri Rad
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  2. Aliasghar Jarrahpour
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Correspondence to Aliasghar Jarrahpour.

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Rad, J.A., Jarrahpour, A., Latour, C. et al. Synthesis and antimicrobial/antimalarial activities of novel naphthalimido trans-β-lactam derivatives. Med Chem Res 26, 2235–2242 (2017). https://doi.org/10.1007/s00044-017-1920-z

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