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

doi:10.1016/j.ejmech.2021.113439

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

Resultado de pesquisa: ???type-name??? › ???researchoutput.researchoutputtypes.contributiontojournal.article??? › revisão de pares

30 Citações (Scopus)

Resumo

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.

Idioma original	???core.languages.en_GB???
Número do artigo	113439
Revista	European Journal of Medicinal Chemistry
Volume	219
DOIs	https://doi.org/10.1016/j.ejmech.2021.113439
Estado da publicação	???researchoutput.status.published??? - 5 jul. 2021

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10.1016/j.ejmech.2021.113439

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Alves, N. G., Bártolo, I., Alves, A. J. S., Fontinha, D., Francisco, D., Lopes, S. M. M., Soares, M. I. L., Simões, C. J. V., Prudêncio, M., Taveira, N., & Pinho e Melo, T. M. V. D. (2021). Synthesis and structure-activity relationships of new chiral spiro-β-lactams highly active against HIV-1 and Plasmodium. European Journal of Medicinal Chemistry, 219, Artigo 113439. https://doi.org/10.1016/j.ejmech.2021.113439

@article{0a48963f009a48e89e13dd85c3512fbe,

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

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.",

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",

author = "Alves, \{Nuno Guerreiro\} and In{\^e}s B{\'a}rtolo and Alves, \{Am{\'e}rico J.S.\} and Diana Fontinha and Denise Francisco and Lopes, \{Susana M.M.\} and Soares, \{Maria I.L.\} and Sim{\~o}es, \{Carlos J.V.\} and Miguel Prud{\^e}ncio and Nuno Taveira and \{Pinho e Melo\}, \{Teresa M.V.D.\}",

note = "Publisher Copyright: {\textcopyright} 2021 Elsevier Masson SAS",

year = "2021",

month = jul,

day = "5",

doi = "10.1016/j.ejmech.2021.113439",

language = "English",

volume = "219",

journal = "European Journal of Medicinal Chemistry",

issn = "0223-5234",

publisher = "Elsevier Masson s.r.l.",

}

Alves, NG, Bártolo, I, Alves, AJS, Fontinha, D, Francisco, D, Lopes, SMM, Soares, MIL, Simões, CJV, Prudêncio, M, Taveira, N & Pinho e Melo, TMVD 2021, 'Synthesis and structure-activity relationships of new chiral spiro-β-lactams highly active against HIV-1 and Plasmodium', European Journal of Medicinal Chemistry, vol. 219, 113439. https://doi.org/10.1016/j.ejmech.2021.113439

Synthesis and structure-activity relationships of new chiral spiro-β-lactams highly active against HIV-1 and Plasmodium. / Alves, Nuno Guerreiro; Bártolo, Inês; Alves, Américo J.S. et al.
Em: European Journal of Medicinal Chemistry, Vol. 219, 113439, 05.07.2021.

Resultado de pesquisa: ???type-name??? › ???researchoutput.researchoutputtypes.contributiontojournal.article??? › revisão de pares

TY - JOUR

T1 - Synthesis and structure-activity relationships of new chiral spiro-β-lactams highly active against HIV-1 and Plasmodium

AU - Alves, Nuno Guerreiro

AU - Bártolo, Inês

AU - Alves, Américo J.S.

AU - Fontinha, Diana

AU - Francisco, Denise

AU - Lopes, Susana M.M.

AU - Soares, Maria I.L.

AU - Simões, Carlos J.V.

AU - Prudêncio, Miguel

AU - Taveira, Nuno

AU - Pinho e Melo, Teresa M.V.D.

PY - 2021/7/5

Y1 - 2021/7/5

N2 - 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.

AB - 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.

KW - 1,3-Dipolar Cycloaddition

KW - 2-butynoates

KW - Allenes

KW - Anti-HIV Agents

KW - Antiplasmodial Agents

KW - Phosphane-catalyzed [3+2] annulations

KW - Spiro-3H-pyrazole-β-lactam

KW - Spiro-penicillanates

KW - Spirocyclic compounds

KW - spirocyclopentenyl-β-lactams

KW - β-Lactams

UR - https://www.scopus.com/pages/publications/85104448348

U2 - 10.1016/j.ejmech.2021.113439

DO - 10.1016/j.ejmech.2021.113439

M3 - Article

C2 - 33887681

AN - SCOPUS:85104448348

SN - 0223-5234

VL - 219

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

M1 - 113439

ER -

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

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