Synthesis of novel isoflavone/benzo-δ-sultam hybrids as potential anti-inflammatory drugs

Gabriel Mengheres; Craig Rice; Olumayokun Olajide; Karl Hemming

doi:10.1016/j.bmcl.2020.127761

Synthesis of novel isoflavone/benzo-δ-sultam hybrids as potential anti-inflammatory drugs

Gabriel Mengheres, Craig Rice, Olumayokun Olajide, Karl Hemming

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

7 Citations (Scopus)

Abstract

A small series of novel isoflavone/benzo-δ-sultam hybrids was synthesised and evaluated as potential anti-inflammatory and neuroprotective drugs in LPS-activated BV2 microglia. The benzo-δ-sultam core was constructed in a two-step reaction by coupling 2-halobenzenesulfonamide derivatives with terminal alkynes, followed by a 6-endo-dig cyclisation. The synthesised compounds, including precursors and hybrids, were tested for their ability to inhibit NO and TNF-α production in LPS-stimulated BV2 microglial cells, and the results are promising. The most potent hybrid reduces the NO production to 41%, and the TNF-α to 34% at 20 µM final concentration in the well.

Original language	English
Article number	127761
Number of pages	8
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	34
Early online date	24 Dec 2020
DOIs	https://doi.org/10.1016/j.bmcl.2020.127761
Publication status	Published - 15 Feb 2021

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Manuscript BMCL Synthesis of novel isoflavone hybrids Revised KH GM_KHfinalAccepted author manuscript, 554 KBLicence: CC BY-NC-ND

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title = "Synthesis of novel isoflavone/benzo-δ-sultam hybrids as potential anti-inflammatory drugs",

abstract = "A small series of novel isoflavone/benzo-δ-sultam hybrids was synthesised and evaluated as potential anti-inflammatory and neuroprotective drugs in LPS-activated BV2 microglia. The benzo-δ-sultam core was constructed in a two-step reaction by coupling 2-halobenzenesulfonamide derivatives with terminal alkynes, followed by a 6-endo-dig cyclisation. The synthesised compounds, including precursors and hybrids, were tested for their ability to inhibit NO and TNF-α production in LPS-stimulated BV2 microglial cells, and the results are promising. The most potent hybrid reduces the NO production to 41%, and the TNF-α to 34% at 20 µM final concentration in the well.",

keywords = "Isoflavone, δ-sultam, Anti-inflammatory, Microglia, TNF-α",

author = "Gabriel Mengheres and Craig Rice and Olumayokun Olajide and Karl Hemming",

note = "Funding Information: We thank the University of Huddersfield for the scholarship (to G.M.). Also, we thank Dr. Neil McLay, University of Huddersfield, for NMR support, and Dr. Jack Blackburn and Dr. Sean Ward, University of Huddersfield, for mass spectrometry support. Publisher Copyright: {\textcopyright} 2020 Elsevier Ltd Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

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doi = "10.1016/j.bmcl.2020.127761",

language = "English",

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T1 - Synthesis of novel isoflavone/benzo-δ-sultam hybrids as potential anti-inflammatory drugs

AU - Mengheres, Gabriel

AU - Rice, Craig

AU - Olajide, Olumayokun

AU - Hemming, Karl

N1 - Funding Information: We thank the University of Huddersfield for the scholarship (to G.M.). Also, we thank Dr. Neil McLay, University of Huddersfield, for NMR support, and Dr. Jack Blackburn and Dr. Sean Ward, University of Huddersfield, for mass spectrometry support. Publisher Copyright: © 2020 Elsevier Ltd Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/2/15

Y1 - 2021/2/15

N2 - A small series of novel isoflavone/benzo-δ-sultam hybrids was synthesised and evaluated as potential anti-inflammatory and neuroprotective drugs in LPS-activated BV2 microglia. The benzo-δ-sultam core was constructed in a two-step reaction by coupling 2-halobenzenesulfonamide derivatives with terminal alkynes, followed by a 6-endo-dig cyclisation. The synthesised compounds, including precursors and hybrids, were tested for their ability to inhibit NO and TNF-α production in LPS-stimulated BV2 microglial cells, and the results are promising. The most potent hybrid reduces the NO production to 41%, and the TNF-α to 34% at 20 µM final concentration in the well.

AB - A small series of novel isoflavone/benzo-δ-sultam hybrids was synthesised and evaluated as potential anti-inflammatory and neuroprotective drugs in LPS-activated BV2 microglia. The benzo-δ-sultam core was constructed in a two-step reaction by coupling 2-halobenzenesulfonamide derivatives with terminal alkynes, followed by a 6-endo-dig cyclisation. The synthesised compounds, including precursors and hybrids, were tested for their ability to inhibit NO and TNF-α production in LPS-stimulated BV2 microglial cells, and the results are promising. The most potent hybrid reduces the NO production to 41%, and the TNF-α to 34% at 20 µM final concentration in the well.

KW - Isoflavone

KW - δ-sultam

KW - Anti-inflammatory

KW - Microglia

KW - TNF-α

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U2 - 10.1016/j.bmcl.2020.127761

DO - 10.1016/j.bmcl.2020.127761

M3 - Article

VL - 34

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

M1 - 127761

ER -

Synthesis of novel isoflavone/benzo-δ-sultam hybrids as potential anti-inflammatory drugs

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