Spiro-β-lactam BSS-730A Displays Potent Activity against HIV and Plasmodium

• DOI: 10.1021/acsinfecdis.0c00768
• Publication Date: 2021-01-04T20:16:54Z
• Authors: Inês Bártolo; Bruna S. Santos; Diana Fontinha; Marta Machado; Denise Francisco; Bruno Sepodes; João Rocha; Hélder Mota-Filipe; Rui Pinto; Maria E. Figueira; Helena Barroso; Teresa Nascimento; António P. Alves ...; Américo J. S. Alves; Nuno G. Alves; Carlos J. V. Simões; Miguel Prudêncio; Teresa M. V. D. P...; Nuno Taveira
• Keywords: Tolerability; Plasmodium berghei; IC50

The high burden of malaria and HIV/AIDS prevents economic social progress in developing countries. A continuing need exists for development novel drugs treatment regimens both diseases order to address the tolerability long-term safety concerns associated with current options emergence drug resistance. We describe new spiro-β-lactam derivatives potent (nM) activity against HIV Plasmodium no bacteria yeast. best performing molecule series, BSS-730A, inhibited HIV-1 HIV-2 replication an IC50 13 ± 9.59 nM P. berghei hepatic infection 0.55 0.14 μM a clear impact on parasite development. BSS-730A was also active erythrocytic stages falciparum, estimated 0.43 0.04 μM. Time-of-addition studies showed that potentially affects all replicative cycle, suggesting complex mechanism action. multidrug-resistant isolates, median 2.4-fold higher relative control isolates. equally R5 X4 isolates displayed strong synergism entry inhibitor AMD3100. is promising candidate as potential therapeutic and/or prophylactic agent Plasmodium.