N-i-Propoxy-N-biphenylsulfonylaminobutylhydroxamic acids as potent and selective inhibitors of MMP-2 and MT1-MMP

Armando Rossello; Elisa Nuti; Paolo Carelli; Elisabetta Orlandini; Marco Macchia; Susanna Nencetti; Maurizio Zandomeneghi; Federica Balzano; Gloria Uccello Barretta; Adriana Albini; Roberto Benelli; Giovanni Cercignani; Gillian Murphy; Aldo Balsamo

doi:10.1016/j.bmcl.2005.01.024

N-i-Propoxy-N-biphenylsulfonylaminobutylhydroxamic acids as potent and selective inhibitors of MMP-2 and MT1-MMP

Armando Rossello, Elisa Nuti, Paolo Carelli, Elisabetta Orlandini, Marco Macchia, Susanna Nencetti, Maurizio Zandomeneghi, Federica Balzano, Gloria Uccello Barretta, Adriana Albini, Roberto Benelli, Giovanni Cercignani, Gillian Murphy, Aldo Balsamo

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

Abstract

Structural manipulation of the pharmacophoric model of type A selective MMP inhibitors (MMPi), obtained by the insertion of some alkyl substituents R ₂ possessing an appropriate geometry, steric bulkiness and lipophilicity, is able to improve potency, in the subnanomolar range on MMP-2, and to give a good MMP inhibition on MMP-14 (MT1-MMP) in the designed MMPi of type C, while maintaining a good MMP-1/MMP-2 selectivity profile. The simultaneous inhibition of these two enzymes yields type C compounds, which are potent antiangiogenic agents, able to block a chemoinvasion model on HUVEC cells in the micromolar range.

Original language	English
Pages (from-to)	1321-1326
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	15
Issue number	5
DOIs	https://doi.org/10.1016/j.bmcl.2005.01.024
Publication status	Published - Mar 1 2005

Keywords

Antiangiogenic agents
MMP-2/MT1-MMP selective inhibitors
MMP-inhibitors

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Organic Chemistry
Drug Discovery
Pharmaceutical Science

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10.1016/j.bmcl.2005.01.024

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Rossello, A., Nuti, E., Carelli, P., Orlandini, E., Macchia, M., Nencetti, S., Zandomeneghi, M., Balzano, F., Barretta, G. U., Albini, A., Benelli, R., Cercignani, G., Murphy, G., & Balsamo, A. (2005). N-i-Propoxy-N-biphenylsulfonylaminobutylhydroxamic acids as potent and selective inhibitors of MMP-2 and MT1-MMP. Bioorganic and Medicinal Chemistry Letters, 15(5), 1321-1326. https://doi.org/10.1016/j.bmcl.2005.01.024

N-i-Propoxy-N-biphenylsulfonylaminobutylhydroxamic acids as potent and selective inhibitors of MMP-2 and MT1-MMP. / Rossello, Armando; Nuti, Elisa; Carelli, Paolo; Orlandini, Elisabetta; Macchia, Marco; Nencetti, Susanna; Zandomeneghi, Maurizio; Balzano, Federica; Barretta, Gloria Uccello; Albini, Adriana ; Benelli, Roberto; Cercignani, Giovanni; Murphy, Gillian; Balsamo, Aldo.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 15, No. 5, 01.03.2005, p. 1321-1326.

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

Rossello, A, Nuti, E, Carelli, P, Orlandini, E, Macchia, M, Nencetti, S, Zandomeneghi, M, Balzano, F, Barretta, GU, Albini, A , Benelli, R, Cercignani, G, Murphy, G & Balsamo, A 2005, 'N-i-Propoxy-N-biphenylsulfonylaminobutylhydroxamic acids as potent and selective inhibitors of MMP-2 and MT1-MMP', Bioorganic and Medicinal Chemistry Letters, vol. 15, no. 5, pp. 1321-1326. https://doi.org/10.1016/j.bmcl.2005.01.024

Rossello, Armando ; Nuti, Elisa ; Carelli, Paolo ; Orlandini, Elisabetta ; Macchia, Marco ; Nencetti, Susanna ; Zandomeneghi, Maurizio ; Balzano, Federica ; Barretta, Gloria Uccello ; Albini, Adriana ; Benelli, Roberto ; Cercignani, Giovanni ; Murphy, Gillian ; Balsamo, Aldo. / N-i-Propoxy-N-biphenylsulfonylaminobutylhydroxamic acids as potent and selective inhibitors of MMP-2 and MT1-MMP. In: Bioorganic and Medicinal Chemistry Letters. 2005 ; Vol. 15, No. 5. pp. 1321-1326.

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abstract = "Structural manipulation of the pharmacophoric model of type A selective MMP inhibitors (MMPi), obtained by the insertion of some alkyl substituents R 2 possessing an appropriate geometry, steric bulkiness and lipophilicity, is able to improve potency, in the subnanomolar range on MMP-2, and to give a good MMP inhibition on MMP-14 (MT1-MMP) in the designed MMPi of type C, while maintaining a good MMP-1/MMP-2 selectivity profile. The simultaneous inhibition of these two enzymes yields type C compounds, which are potent antiangiogenic agents, able to block a chemoinvasion model on HUVEC cells in the micromolar range.",

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AU - Orlandini, Elisabetta

AU - Macchia, Marco

AU - Nencetti, Susanna

AU - Zandomeneghi, Maurizio

AU - Balzano, Federica

AU - Barretta, Gloria Uccello

AU - Albini, Adriana

AU - Benelli, Roberto

AU - Cercignani, Giovanni

AU - Murphy, Gillian

AU - Balsamo, Aldo

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AB - Structural manipulation of the pharmacophoric model of type A selective MMP inhibitors (MMPi), obtained by the insertion of some alkyl substituents R 2 possessing an appropriate geometry, steric bulkiness and lipophilicity, is able to improve potency, in the subnanomolar range on MMP-2, and to give a good MMP inhibition on MMP-14 (MT1-MMP) in the designed MMPi of type C, while maintaining a good MMP-1/MMP-2 selectivity profile. The simultaneous inhibition of these two enzymes yields type C compounds, which are potent antiangiogenic agents, able to block a chemoinvasion model on HUVEC cells in the micromolar range.

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N-i-Propoxy-N-biphenylsulfonylaminobutylhydroxamic acids as potent and selective inhibitors of MMP-2 and MT1-MMP

Abstract

Keywords

ASJC Scopus subject areas

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