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

• Author(s): 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.
• Date: 2021
• Persistent ID: https://hdl.handle.net/10316/107437
• Origin: Estudo Geral - Universidade de Coimbra
• Subject(s): 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; Anti-HIV Agents; Antimalarials; Cell Line; Cell Survival; Drug Design; HIV-1; Humans; Life Cycle Stages; Molecular Conformation; Plasmodium; Spiro Compounds; Stereoisomerism; Structure-Activity Relationship; beta-Lactams
• Document Type: Journal article
• Language: English

Description

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.