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. 2019 Spring;18(2):596-606.
doi: 10.22037/ijpr.2017.2024.

Diastereoselective Synthesis of Potent Antimalarial Cis-β-lactam Agents

Aliasghar Jarrahpour  1 , Maryam Rostami  1 , Véronique Sinou  2 , Christine Latour  2 , Lamia Djouhri-Bouktab  3 , Jean Michel Brunel  3
Affiliations

Diastereoselective Synthesis of Potent Antimalarial Cis-β-lactam Agents

Aliasghar Jarrahpour et al. Iran J Pharm Res. 2019 Spring.

Abstract

Fifteen novel β-lactams bearing N-ethyl tert-butyl carbamate group 5a-o and fifteen N-(2- aminoethyl) β-lactams 6a-o were synthesized by [2+2] ketene-imine cycloaddition reaction (Staudinger). The cycloaddition reaction was found to be totally diastereoselective leading exclusively to theformation of cis-β-lactam derivatives. These newly synthesized β-lactams were evaluated for their antimalarial activity against p. falciparum K14 resistant strain and showed good to excellent EC50 values. Of the thirty β-lactams tested, 5 h, 6a and 6c showed IC50 < 20 µM while 5b, 5c, 5e, 5f, 5g, 5i, 5j, 6d, 6g and 6h exhibited IC50 <50 . Compounds 5c, 5h, and 5q-t were examined for their anticancer properties against K562 Leukemia cell line and 5s showed the best activity. Compounds 3a-j, 5a-o, 6a-o, were tested against S. aureus , E. coli, C. albicans and showed no activity below 125 µg/mL.

Keywords: 2-Azetidinones; Antimalarial activity; N-(2-aminoethyl) β-lactams; P. falciparum; Staudinger; tert-butyl carbamate.

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Figures

Scheme 1
Scheme 1
Synthesis of cis-β-lactams 5a-o and 6a-o
See this image and copyright information in PMC

References

    1. Kar S, Kar S. Control of malaria. Nat. Rev. Drug Discov. 2010;9:511–2. - PubMed
    1. Aviles E, Rodriguez AD. Monamphilectine A, a Potent Antimalarial β-Lactam from Marine Sponge Hymeniacidon sp: Isolation, Structure, Semisynthesis, and Bioactivity Org. Lett. 2010;12:5290–3. - PMC - PubMed
    1. Ridley RG. Planting the seeds of new antimalarial drugs. Science. 1999;285:1502–150. - PubMed
    1. Peters W. Chemotherapy and Drug Resistance in Malaria. 2nd ed. London: Academic; 1987.
    1. Jarrahpour A, Ebrahimi E, De Clercq E, Sinou V, Latour C, Bouktab LD, Brunel JM. Synthesis of mono-, bis-spiro- and dispiro-b-lactams and evaluation of their antimalarial activities. Tetrahedron. 2011;67:8699–704.

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