Synthesis and structure-activity relationships of new chiral spiro-β-lactams highly active against HIV-1 and Plasmodium

The synthesis and antimicrobial activity of new spiro-β-lactams is reported. The design of the new molecules was based on the structural modulation of two previously identified lead spiro-penicillanates with dual activity against HIV and Plasmodium. The spiro-β-lactams synthesized were assayed for t...

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Bibliographic Details
Published in:	European journal of medicinal chemistry 2021-07, Vol.219, p.113439-113439, Article 113439
Main Authors:	Alves, Nuno Guerreiro, Bártolo, Inês, Alves, Américo J.S., Fontinha, Diana, Francisco, Denise, Lopes, Susana M.M., Soares, Maria I.L., Simões, Carlos J.V., Prudêncio, Miguel, Taveira, Nuno, Pinho e Melo, Teresa M.V.D.
Format:	Article
Language:	eng
Subjects:	1,3-Dipolar cycloaddition 2-Butynoates Allenes Anti-HIV agents Antiplasmodial agents Phosphane-catalyzed [3+2] annulations Spiro-3H-pyrazole-β-lactams Spiro-penicillanates Spirocyclic compounds Spirocyclopentenyl-β-lactams β-Lactams
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Summary:	The synthesis and antimicrobial activity of new spiro-β-lactams is reported. The design of the new molecules was based on the structural modulation of two previously identified lead spiro-penicillanates with dual activity against HIV and Plasmodium. The spiro-β-lactams synthesized were assayed for their in vitro activity against HIV-1, providing relevant structure-activity relationship information. Among the tested compounds, two spirocyclopentenyl-β-lactams were identified as having remarkable nanomolar activity against HIV-1. Additionally, the same molecules showed promising antiplasmodial activity, inhibiting both the hepatic and blood stages of Plasmodium infection. [Display omitted] •Structural modulation of lead compounds led to synthesis of twenty-three new spirocyclic β-lactams.•Anti-HIV-1 activity studies provided relevant information concerning structure-activity relationships.•Two new spirocyclopentenyl-β-lactams showed outstanding dual activity against HIV-1 and Plasmodium.•The potential of spiro-penicillanates as highly promising anti-microbial agents was strengthen.
ISSN:	0223-5234 1768-3254