1-(2-Hydroxy-5-((trimethylsilyl)ethynyl)phenyl)ethanone based α,β-unsaturated derivatives an alternate to non-sulfonamide carbonic anhydrase II inhibitors, synthesis via Sonogashira coupling, binding analysis, Lipinsk's rule validation

Jamaluddin Mahar, Aamer Saeed, Kevin Belfield, Fayaz Ali Larik, Pervaiz Ali Channar, Mehar Ali Kazi, Qamar Abbas, Mubashir Hassan, Hussain Raza, Sung Yum Seo

Research output: Contribution to journalArticle

Abstract

A novel series of silyl-yne containing chalcone derivatives 5a-5j was synthesized by exploiting Sonogashira coupling reaction and Claisen-Schimdt condensation reaction. The synthesized derivative were characterized by spectroscopic and elemental analysis. The selective inhibition of carbonic anhydrases is considered critical in the field of medicinal chemistry because carbonic anhydrases exits in several isoforms. Synthesized compounds were subjected to carbonic anhydrase –II assay. Except 5j, the other derivatives exhibited better potential than standard acetazolamide. Compound 5e was found to be potent derivative in the series with IC 50 value 0.054 ± 0.001 µM. Binding analysis revealed that most potent derivative 5e binds in the active site of CA-II and single π-π stacking interaction was observed between ring structure of ligand and Phe129 having bond length 4.90 Å. Pharmacokinetics elicited that compounds obey Lipinski's rule and show significant drug score.

Original languageEnglish (US)
Pages (from-to)170-176
Number of pages7
JournalBioorganic Chemistry
Volume84
DOIs
StatePublished - Mar 1 2019
Externally publishedYes

Fingerprint

Carbonic Anhydrase II
Carbonic Anhydrase Inhibitors
Carbonic Anhydrases
Derivatives
Chalcone
Acetazolamide
Pharmaceutical Chemistry
Catalytic Domain
Protein Isoforms
Pharmacokinetics
Ligands
Condensation reactions
Spectroscopic analysis
Pharmaceutical Preparations
Bond length
Assays
Chemical analysis

All Science Journal Classification (ASJC) codes

  • Drug Discovery
  • Molecular Biology
  • Biochemistry
  • Organic Chemistry

Cite this

Mahar, Jamaluddin ; Saeed, Aamer ; Belfield, Kevin ; Ali Larik, Fayaz ; Ali Channar, Pervaiz ; Ali Kazi, Mehar ; Abbas, Qamar ; Hassan, Mubashir ; Raza, Hussain ; Seo, Sung Yum. / 1-(2-Hydroxy-5-((trimethylsilyl)ethynyl)phenyl)ethanone based α,β-unsaturated derivatives an alternate to non-sulfonamide carbonic anhydrase II inhibitors, synthesis via Sonogashira coupling, binding analysis, Lipinsk's rule validation. In: Bioorganic Chemistry. 2019 ; Vol. 84. pp. 170-176.
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abstract = "A novel series of silyl-yne containing chalcone derivatives 5a-5j was synthesized by exploiting Sonogashira coupling reaction and Claisen-Schimdt condensation reaction. The synthesized derivative were characterized by spectroscopic and elemental analysis. The selective inhibition of carbonic anhydrases is considered critical in the field of medicinal chemistry because carbonic anhydrases exits in several isoforms. Synthesized compounds were subjected to carbonic anhydrase –II assay. Except 5j, the other derivatives exhibited better potential than standard acetazolamide. Compound 5e was found to be potent derivative in the series with IC 50 value 0.054 ± 0.001 µM. Binding analysis revealed that most potent derivative 5e binds in the active site of CA-II and single π-π stacking interaction was observed between ring structure of ligand and Phe129 having bond length 4.90 {\AA}. Pharmacokinetics elicited that compounds obey Lipinski's rule and show significant drug score.",
author = "Jamaluddin Mahar and Aamer Saeed and Kevin Belfield and {Ali Larik}, Fayaz and {Ali Channar}, Pervaiz and {Ali Kazi}, Mehar and Qamar Abbas and Mubashir Hassan and Hussain Raza and Seo, {Sung Yum}",
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1-(2-Hydroxy-5-((trimethylsilyl)ethynyl)phenyl)ethanone based α,β-unsaturated derivatives an alternate to non-sulfonamide carbonic anhydrase II inhibitors, synthesis via Sonogashira coupling, binding analysis, Lipinsk's rule validation. / Mahar, Jamaluddin; Saeed, Aamer; Belfield, Kevin; Ali Larik, Fayaz; Ali Channar, Pervaiz; Ali Kazi, Mehar; Abbas, Qamar; Hassan, Mubashir; Raza, Hussain; Seo, Sung Yum.

In: Bioorganic Chemistry, Vol. 84, 01.03.2019, p. 170-176.

Research output: Contribution to journalArticle

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AU - Mahar, Jamaluddin

AU - Saeed, Aamer

AU - Belfield, Kevin

AU - Ali Larik, Fayaz

AU - Ali Channar, Pervaiz

AU - Ali Kazi, Mehar

AU - Abbas, Qamar

AU - Hassan, Mubashir

AU - Raza, Hussain

AU - Seo, Sung Yum

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AB - A novel series of silyl-yne containing chalcone derivatives 5a-5j was synthesized by exploiting Sonogashira coupling reaction and Claisen-Schimdt condensation reaction. The synthesized derivative were characterized by spectroscopic and elemental analysis. The selective inhibition of carbonic anhydrases is considered critical in the field of medicinal chemistry because carbonic anhydrases exits in several isoforms. Synthesized compounds were subjected to carbonic anhydrase –II assay. Except 5j, the other derivatives exhibited better potential than standard acetazolamide. Compound 5e was found to be potent derivative in the series with IC 50 value 0.054 ± 0.001 µM. Binding analysis revealed that most potent derivative 5e binds in the active site of CA-II and single π-π stacking interaction was observed between ring structure of ligand and Phe129 having bond length 4.90 Å. Pharmacokinetics elicited that compounds obey Lipinski's rule and show significant drug score.

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