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

Nuno Guerreiro Alves, Inês Bártolo, Américo J.S. Alves, Diana Fontinha, Denise Francisco, Susana M.M. Lopes, Maria I.L. Soares, Carlos J.V. Simões, Miguel Prudêncio, Nuno Taveira, Teresa M.V.D. Pinho e Melo

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

The synthesis and anti-microbial 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.

Original languageEnglish
Article number113439
JournalEuropean Journal of Medicinal Chemistry
Volume219
DOIs
Publication statusPublished - 5 Jul 2021

Keywords

  • 1,3-Dipolar Cycloaddition
  • 2-butynoates
  • Allenes
  • Anti-HIV Agents
  • Antiplasmodial Agents
  • Phosphane-catalyzed [3+2] annulations
  • Spiro-3H-pyrazole-β-lactam
  • Spiro-penicillanates
  • Spirocyclic compounds
  • spirocyclopentenyl-β-lactams
  • β-Lactams

Fingerprint

Dive into the research topics of 'Synthesis and structure-activity relationships of new chiral spiro-β-lactams highly active against HIV-1 and Plasmodium'. Together they form a unique fingerprint.

Cite this