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

• Autor(a) principal: Alves, Nuno Guerreiro
• Data de Publicação: 2021
• Outros Autores: 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.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10316/107437; https://doi.org/10.1016/j.ejmech.2021.113439
• topic: 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

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.