Synthesis and structure-activity relationships of new chiral spiro-ß-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 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.

Keywords

Anti-HIV Agents Antiplasmodial Agents Spiro-penicillanates b-Lactams Spirocyclic compounds Spiro-3H-pyrazole-b-lactam spirocyclopentenyl-b-lactams 1,3-Dipolar Cycloaddition Phosphane-catalyzed [3þ2] annulations Allenes 2-butynoates

URI

http://hdl.handle.net/10451/58949

Citation

Alves NG, Bártolo I, Alves AJS, Fontinha D, Francisco D, Lopes SMM, et al. Synthesis and structure-activity relationships of new chiral spiro-β-lactams highly active against HIV-1 and Plasmodium. European Journal of Medicinal Chemistry [Internet]. 5 de julho de 2021;219:113439. Disponível em: https://www.sciencedirect.com/science/article/pii/S0223523421002889