Synthesis and antimicrobial/antimalarial activities of novel naphthalimido trans-β-lactam derivatives
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.
Keywordsβ-Lactam 1,8-Naphthalimide Staudinger reaction Alrestatin Antimalarial
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).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
- Alcaide B, Aragoncillo C, Almendros P (2008) Comprehensive heterocyclic chemistry III. Taylor ARKARFVSJK (ed.), 111–171Google Scholar
- Armarego W, Chai C (2003) Purification of laboratory chemicals, 5th edn. Butter Worth, OxfordGoogle Scholar
- Coates C, Kabir J, Turos E (2005) β-Lactams. Compounds with Four and Three Carbon-Heteroatom Bonds. Houben-Weyl Met Mol Trans 21.9:609–646Google Scholar
- Jung SO, Yuan W, Ju JU, Zhang S, Kim YH, Je JT, Kwon SK (2009) A new orange-light-emitting materials based on (N-naphthyl)-1, 8-naphthalimide for OLED applications. Mol Cryst Liq Cryst 514:45/–54/Google Scholar
- Kaddouri H, Nakache S, Houzé S, Mentré F, Le Bras J (2006) Assessment of the drug susceptibility of Plasmodium falciparum clinical isolates from africa by using a Plasmodium lactate dehydrogenase immunodetection assay and an inhibitory maximum effect model for precise measurement of the 50-percent inhibitory concentration. Antimicrob Agents Chemother 50:3343–3349CrossRefPubMedPubMedCentralGoogle Scholar
- Morin RB, Gorman M (eds) (1982) Chemistry and Biology of β-Lactam Antibiotics. Vol 1–3, Academic Press: New York, NY, USAGoogle Scholar
- Rosenblum SB, Huynh T, Afonso A, Davis HR, Yumibe N, Clader JW, Burnett DA (1998) Discovery of 1-(4-fluorophenyl)-(3 R)-[3-(4-fluorophenyl)-(3 S)-hydroxypropyl]-(4 S)-(4-hydroxyphenyl)-2-azetidinone (SCH 58235): a designed, potent, orally active inhibitor of cholesterol absorption. J Med Chem 41:973–980CrossRefPubMedGoogle Scholar
- Stolarski R (2009) Fluorescent naphthalimide dyes for polyester fibres. Fibres Text East Eur 17:91–95Google Scholar
- Wild H, Georg G (1993) The organic chemistry of β-lactams. VCH, New York, NYGoogle Scholar