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

Research output: Contribution to journal › Article › peer-review

27 Citations (Scopus)

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.

Original language	English
Article number	113439
Journal	European Journal of Medicinal Chemistry
Volume	219
DOIs	https://doi.org/10.1016/j.ejmech.2021.113439
Publication status	Published - 5 Jul 2021

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.ejmech.2021.113439

Cite this

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, Article 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

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

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this