Novel quinolinonyl diketo acid derivatives as HIV-1 integrase inhibitors: Design, synthesis, and biological activities

Roberto Di Santo, Roberta Costi, Alessandra Roux, Gaetano Miele, Giuliana Cuzzucoli Crucitti, Alberto Iacovo, Federica Rosi, Antonio Lavecchia, Luciana Marinelli, Carmen Di Giovanni, Ettore Novellino, Lucia Palmisano, Mauro Andreotti, Roberta Amici, Clementina Maria Galluzzo, Lucia Nencioni, Anna Teresa Palamara, Yves Pommier, Christophe Marchand

Research output: Contribution to journalArticle

Abstract

Novel quinolinonyl diketo acids were designed to obtain integrase (IN) inhibitors selectively active against the strand transfer (ST) step of the HIV integration process. Those new compounds are characterized by a single aryl diketo acid (DKA) chain in comparison to 4, a bifunctional diketo acid reported by our group as an anti-IN agent highly potent against both the 3′-processing and ST steps. Compound 6d was the most potent derivative in IN enzyme assays, while 6i showed the highest potency against HIV-1 in acutely infected cells. The selective inhibition of ST suggested the newly designed monofunctional DKAs bind the IN-DNA acceptor site without affecting the DNA donor site.

Original languageEnglish
Pages (from-to)4744-4750
Number of pages7
JournalJournal of Medicinal Chemistry
Volume51
Issue number15
DOIs
Publication statusPublished - Aug 14 2008

Fingerprint

HIV Integrase Inhibitors
Integrase Inhibitors
Integrases
Bioactivity
Derivatives
Acids
DNA
Enzyme Assays
HIV-1
Assays
HIV
Enzymes
Processing
p31 integrase protein, Human immunodeficiency virus 1

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Di Santo, R., Costi, R., Roux, A., Miele, G., Crucitti, G. C., Iacovo, A., ... Marchand, C. (2008). Novel quinolinonyl diketo acid derivatives as HIV-1 integrase inhibitors: Design, synthesis, and biological activities. Journal of Medicinal Chemistry, 51(15), 4744-4750. https://doi.org/10.1021/jm8001422

Novel quinolinonyl diketo acid derivatives as HIV-1 integrase inhibitors : Design, synthesis, and biological activities. / Di Santo, Roberto; Costi, Roberta; Roux, Alessandra; Miele, Gaetano; Crucitti, Giuliana Cuzzucoli; Iacovo, Alberto; Rosi, Federica; Lavecchia, Antonio; Marinelli, Luciana; Di Giovanni, Carmen; Novellino, Ettore; Palmisano, Lucia; Andreotti, Mauro; Amici, Roberta; Galluzzo, Clementina Maria; Nencioni, Lucia; Palamara, Anna Teresa; Pommier, Yves; Marchand, Christophe.

In: Journal of Medicinal Chemistry, Vol. 51, No. 15, 14.08.2008, p. 4744-4750.

Research output: Contribution to journalArticle

Di Santo, R, Costi, R, Roux, A, Miele, G, Crucitti, GC, Iacovo, A, Rosi, F, Lavecchia, A, Marinelli, L, Di Giovanni, C, Novellino, E, Palmisano, L, Andreotti, M, Amici, R, Galluzzo, CM, Nencioni, L, Palamara, AT, Pommier, Y & Marchand, C 2008, 'Novel quinolinonyl diketo acid derivatives as HIV-1 integrase inhibitors: Design, synthesis, and biological activities', Journal of Medicinal Chemistry, vol. 51, no. 15, pp. 4744-4750. https://doi.org/10.1021/jm8001422
Di Santo, Roberto ; Costi, Roberta ; Roux, Alessandra ; Miele, Gaetano ; Crucitti, Giuliana Cuzzucoli ; Iacovo, Alberto ; Rosi, Federica ; Lavecchia, Antonio ; Marinelli, Luciana ; Di Giovanni, Carmen ; Novellino, Ettore ; Palmisano, Lucia ; Andreotti, Mauro ; Amici, Roberta ; Galluzzo, Clementina Maria ; Nencioni, Lucia ; Palamara, Anna Teresa ; Pommier, Yves ; Marchand, Christophe. / Novel quinolinonyl diketo acid derivatives as HIV-1 integrase inhibitors : Design, synthesis, and biological activities. In: Journal of Medicinal Chemistry. 2008 ; Vol. 51, No. 15. pp. 4744-4750.
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