Synthesis of Symmetrical Monocarbonyl Analogs of Curcumin Containing a 2-Bromobenzylidene Moiety and Spectrophotometric Assessment of Their Reactivity with 2-(Dimethylamino)ethanthiol

The cross-conjugated dienones containing the 1,5-diaryl-3-oxo-1,4-pentadienyl pharmacophore have diverse biological activities. These sometimes-called monocarbonyl analogs of curcumin (MACs) have especially pronounced biological activity when containing an electron-withdrawing group at the ortho-pos...

Full description

Saved in:
Bibliographic Details
Main Authors: Zlatko Lozanovski, Ivana Todorovska, Katerina Dragarska, Jane Bogdanov
Format: Article
Language:English
Published: MDPI AG 2023-11-01
Series:Chemistry Proceedings
Subjects:
Online Access:https://www.mdpi.com/2673-4583/14/1/7
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1846105355102191616
author Zlatko Lozanovski
Ivana Todorovska
Katerina Dragarska
Jane Bogdanov
author_facet Zlatko Lozanovski
Ivana Todorovska
Katerina Dragarska
Jane Bogdanov
author_sort Zlatko Lozanovski
collection DOAJ
description The cross-conjugated dienones containing the 1,5-diaryl-3-oxo-1,4-pentadienyl pharmacophore have diverse biological activities. These sometimes-called monocarbonyl analogs of curcumin (MACs) have especially pronounced biological activity when containing an electron-withdrawing group at the ortho-position of the benzene ring. Their biological activity most likely stems from a selective Michael reaction with thiols. It has been reported in the literature that certain MACs (in particular, <b>EF24</b>) react as electrophiles with glutathione and form bis adducts in vitro. Five MACs were prepared ((<i>2E</i>,<i>5E</i>)-2,5-bis(2-bromobenzylidene)cyclopentanone, (<b>2BrCP</b>), (<i>2E</i>,<i>6E</i>)-2,6-bis(2-bromobenzylidene)cyclohexanone (<b>2BrCX</b>, <b>B2BrBC</b>), (<i>2E</i>,<i>6E</i>)-2,6-bis(2-bromobenzylidene)- 4-<i>tert</i>-butyl-cyclohexanone (<b>4tB2BrCX</b>), (3<i>E</i>,5<i>E</i>)-3,5-bis(2-bromobenzylidene)-4-piperidone, (<b>2Br4PIP</b>) and (<i>3E</i>,<i>5E</i>)-3,5-bis(2-fluorobenzylidene)-4-piperidone, <b>EF24</b>), purified and characterized by spectroscopic means. The relative reactivity of these MACs towards 2-(dimethylamino)ethanethiol was assessed via a previously developed UV-Vis spectroscopic method and compared to <b>EF24</b>, which reacts readily in solution with thiols such as glutathione and cysteamine. All of the bis(2-bromobenzylidene) MACs react slower with 2-(dimethylamino)ethanethiol in 80:20 (v/v) acetonitrile/water compared to <b>EF24</b>. The relative reactivity of the analogs with 2-(dimethylamino)ethanethiol followed the order <b>EF24</b> > <b>2Br4PIP</b> > <b>2BrCX</b> > <b>2BrCP</b> > <b>4tB2BrCX</b>.
format Article
id doaj-art-6fd14adf68e048fbb0ab9b0bac8ff1ac
institution Kabale University
issn 2673-4583
language English
publishDate 2023-11-01
publisher MDPI AG
record_format Article
series Chemistry Proceedings
spelling doaj-art-6fd14adf68e048fbb0ab9b0bac8ff1ac2024-12-27T14:17:16ZengMDPI AGChemistry Proceedings2673-45832023-11-01141710.3390/ecsoc-27-16084Synthesis of Symmetrical Monocarbonyl Analogs of Curcumin Containing a 2-Bromobenzylidene Moiety and Spectrophotometric Assessment of Their Reactivity with 2-(Dimethylamino)ethanthiolZlatko Lozanovski0Ivana Todorovska1Katerina Dragarska2Jane Bogdanov3Higher Medical School, St. Kliment Ohridski University, Partizanska bb, 7000 Bitola, North MacedoniaInstitute of Chemistry, Faculty of Natural Sciences and Mathematics, Ss. Cyril and Methodius University in Skopje, Arhimedova 5, 1000 Skopje, North MacedoniaInstitute of Chemistry, Faculty of Natural Sciences and Mathematics, Ss. Cyril and Methodius University in Skopje, Arhimedova 5, 1000 Skopje, North MacedoniaInstitute of Chemistry, Faculty of Natural Sciences and Mathematics, Ss. Cyril and Methodius University in Skopje, Arhimedova 5, 1000 Skopje, North MacedoniaThe cross-conjugated dienones containing the 1,5-diaryl-3-oxo-1,4-pentadienyl pharmacophore have diverse biological activities. These sometimes-called monocarbonyl analogs of curcumin (MACs) have especially pronounced biological activity when containing an electron-withdrawing group at the ortho-position of the benzene ring. Their biological activity most likely stems from a selective Michael reaction with thiols. It has been reported in the literature that certain MACs (in particular, <b>EF24</b>) react as electrophiles with glutathione and form bis adducts in vitro. Five MACs were prepared ((<i>2E</i>,<i>5E</i>)-2,5-bis(2-bromobenzylidene)cyclopentanone, (<b>2BrCP</b>), (<i>2E</i>,<i>6E</i>)-2,6-bis(2-bromobenzylidene)cyclohexanone (<b>2BrCX</b>, <b>B2BrBC</b>), (<i>2E</i>,<i>6E</i>)-2,6-bis(2-bromobenzylidene)- 4-<i>tert</i>-butyl-cyclohexanone (<b>4tB2BrCX</b>), (3<i>E</i>,5<i>E</i>)-3,5-bis(2-bromobenzylidene)-4-piperidone, (<b>2Br4PIP</b>) and (<i>3E</i>,<i>5E</i>)-3,5-bis(2-fluorobenzylidene)-4-piperidone, <b>EF24</b>), purified and characterized by spectroscopic means. The relative reactivity of these MACs towards 2-(dimethylamino)ethanethiol was assessed via a previously developed UV-Vis spectroscopic method and compared to <b>EF24</b>, which reacts readily in solution with thiols such as glutathione and cysteamine. All of the bis(2-bromobenzylidene) MACs react slower with 2-(dimethylamino)ethanethiol in 80:20 (v/v) acetonitrile/water compared to <b>EF24</b>. The relative reactivity of the analogs with 2-(dimethylamino)ethanethiol followed the order <b>EF24</b> > <b>2Br4PIP</b> > <b>2BrCX</b> > <b>2BrCP</b> > <b>4tB2BrCX</b>.https://www.mdpi.com/2673-4583/14/1/7monocarbonyl analogs of curcuminsymmetrical 2-bromobenzylidene MACssynthesis2-(dimethylamino)ethanethiolMichael reaction with thiolsUV-Vis spectroscopy
spellingShingle Zlatko Lozanovski
Ivana Todorovska
Katerina Dragarska
Jane Bogdanov
Synthesis of Symmetrical Monocarbonyl Analogs of Curcumin Containing a 2-Bromobenzylidene Moiety and Spectrophotometric Assessment of Their Reactivity with 2-(Dimethylamino)ethanthiol
Chemistry Proceedings
monocarbonyl analogs of curcumin
symmetrical 2-bromobenzylidene MACs
synthesis
2-(dimethylamino)ethanethiol
Michael reaction with thiols
UV-Vis spectroscopy
title Synthesis of Symmetrical Monocarbonyl Analogs of Curcumin Containing a 2-Bromobenzylidene Moiety and Spectrophotometric Assessment of Their Reactivity with 2-(Dimethylamino)ethanthiol
title_full Synthesis of Symmetrical Monocarbonyl Analogs of Curcumin Containing a 2-Bromobenzylidene Moiety and Spectrophotometric Assessment of Their Reactivity with 2-(Dimethylamino)ethanthiol
title_fullStr Synthesis of Symmetrical Monocarbonyl Analogs of Curcumin Containing a 2-Bromobenzylidene Moiety and Spectrophotometric Assessment of Their Reactivity with 2-(Dimethylamino)ethanthiol
title_full_unstemmed Synthesis of Symmetrical Monocarbonyl Analogs of Curcumin Containing a 2-Bromobenzylidene Moiety and Spectrophotometric Assessment of Their Reactivity with 2-(Dimethylamino)ethanthiol
title_short Synthesis of Symmetrical Monocarbonyl Analogs of Curcumin Containing a 2-Bromobenzylidene Moiety and Spectrophotometric Assessment of Their Reactivity with 2-(Dimethylamino)ethanthiol
title_sort synthesis of symmetrical monocarbonyl analogs of curcumin containing a 2 bromobenzylidene moiety and spectrophotometric assessment of their reactivity with 2 dimethylamino ethanthiol
topic monocarbonyl analogs of curcumin
symmetrical 2-bromobenzylidene MACs
synthesis
2-(dimethylamino)ethanethiol
Michael reaction with thiols
UV-Vis spectroscopy
url https://www.mdpi.com/2673-4583/14/1/7
work_keys_str_mv AT zlatkolozanovski synthesisofsymmetricalmonocarbonylanalogsofcurcumincontaininga2bromobenzylidenemoietyandspectrophotometricassessmentoftheirreactivitywith2dimethylaminoethanthiol
AT ivanatodorovska synthesisofsymmetricalmonocarbonylanalogsofcurcumincontaininga2bromobenzylidenemoietyandspectrophotometricassessmentoftheirreactivitywith2dimethylaminoethanthiol
AT katerinadragarska synthesisofsymmetricalmonocarbonylanalogsofcurcumincontaininga2bromobenzylidenemoietyandspectrophotometricassessmentoftheirreactivitywith2dimethylaminoethanthiol
AT janebogdanov synthesisofsymmetricalmonocarbonylanalogsofcurcumincontaininga2bromobenzylidenemoietyandspectrophotometricassessmentoftheirreactivitywith2dimethylaminoethanthiol