Elucidation of Antimicrobials and Biofilm Inhibitors Derived from a Polyacetylene Core

The development of new antibiotics with unique mechanisms of action is paramount to combating the growing threat of antibiotic resistance. Recently, based on inspiration from natural products, an asymmetrical polyacetylene core structure was examined for its bioactivity and found to have differentia...

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Main Authors: Tyler L. Skeen, Rebekah L. Gresham, Katherine A. Agamaite, Olivia M. Molz, Isabelle F. Westlake, Sage M. Kregenow, Al K. Romero, Brian M. Flood, Lauren E. Mazur, Robert J. Hinkle, Douglas D. Young
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/29/24/5945
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author Tyler L. Skeen
Rebekah L. Gresham
Katherine A. Agamaite
Olivia M. Molz
Isabelle F. Westlake
Sage M. Kregenow
Al K. Romero
Brian M. Flood
Lauren E. Mazur
Robert J. Hinkle
Douglas D. Young
author_facet Tyler L. Skeen
Rebekah L. Gresham
Katherine A. Agamaite
Olivia M. Molz
Isabelle F. Westlake
Sage M. Kregenow
Al K. Romero
Brian M. Flood
Lauren E. Mazur
Robert J. Hinkle
Douglas D. Young
author_sort Tyler L. Skeen
collection DOAJ
description The development of new antibiotics with unique mechanisms of action is paramount to combating the growing threat of antibiotic resistance. Recently, based on inspiration from natural products, an asymmetrical polyacetylene core structure was examined for its bioactivity and found to have differential specificity for different bacterial species based on the substituents around the conjugated alkyne. This research further probes the structural requirements for bioactivity through a systematic synthesis and investigation of new compounds with variable carbon chain length, alkynyl subunits, and alcohol substitution. Furthermore, the research examines the activity of the new compounds towards the inhibition of biofilm formation. Overall, several key new polyyne compounds have been identified in both decreasing bacterial viability and in disrupting pre-formed biofilms. These properties are key in the fight against bacterial infections and will be helpful in the further development of new antibiotic agents.
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spelling doaj-art-0214c84781a047cc8aebaf0949b7568d2025-08-20T02:01:20ZengMDPI AGMolecules1420-30492024-12-012924594510.3390/molecules29245945Elucidation of Antimicrobials and Biofilm Inhibitors Derived from a Polyacetylene CoreTyler L. Skeen0Rebekah L. Gresham1Katherine A. Agamaite2Olivia M. Molz3Isabelle F. Westlake4Sage M. Kregenow5Al K. Romero6Brian M. Flood7Lauren E. Mazur8Robert J. Hinkle9Douglas D. Young10Department of Chemistry, William & Mary, Williamsburg, VA 23185, USADepartment of Chemistry, William & Mary, Williamsburg, VA 23185, USADepartment of Chemistry, William & Mary, Williamsburg, VA 23185, USADepartment of Chemistry, William & Mary, Williamsburg, VA 23185, USADepartment of Chemistry, William & Mary, Williamsburg, VA 23185, USADepartment of Chemistry, William & Mary, Williamsburg, VA 23185, USADepartment of Chemistry, William & Mary, Williamsburg, VA 23185, USADepartment of Chemistry, William & Mary, Williamsburg, VA 23185, USADepartment of Chemistry, William & Mary, Williamsburg, VA 23185, USADepartment of Chemistry, William & Mary, Williamsburg, VA 23185, USADepartment of Chemistry, William & Mary, Williamsburg, VA 23185, USAThe development of new antibiotics with unique mechanisms of action is paramount to combating the growing threat of antibiotic resistance. Recently, based on inspiration from natural products, an asymmetrical polyacetylene core structure was examined for its bioactivity and found to have differential specificity for different bacterial species based on the substituents around the conjugated alkyne. This research further probes the structural requirements for bioactivity through a systematic synthesis and investigation of new compounds with variable carbon chain length, alkynyl subunits, and alcohol substitution. Furthermore, the research examines the activity of the new compounds towards the inhibition of biofilm formation. Overall, several key new polyyne compounds have been identified in both decreasing bacterial viability and in disrupting pre-formed biofilms. These properties are key in the fight against bacterial infections and will be helpful in the further development of new antibiotic agents.https://www.mdpi.com/1420-3049/29/24/5945antibioticsalkynesbiofilmsstructure–activity relationshipsGlaser–Hay reaction
spellingShingle Tyler L. Skeen
Rebekah L. Gresham
Katherine A. Agamaite
Olivia M. Molz
Isabelle F. Westlake
Sage M. Kregenow
Al K. Romero
Brian M. Flood
Lauren E. Mazur
Robert J. Hinkle
Douglas D. Young
Elucidation of Antimicrobials and Biofilm Inhibitors Derived from a Polyacetylene Core
Molecules
antibiotics
alkynes
biofilms
structure–activity relationships
Glaser–Hay reaction
title Elucidation of Antimicrobials and Biofilm Inhibitors Derived from a Polyacetylene Core
title_full Elucidation of Antimicrobials and Biofilm Inhibitors Derived from a Polyacetylene Core
title_fullStr Elucidation of Antimicrobials and Biofilm Inhibitors Derived from a Polyacetylene Core
title_full_unstemmed Elucidation of Antimicrobials and Biofilm Inhibitors Derived from a Polyacetylene Core
title_short Elucidation of Antimicrobials and Biofilm Inhibitors Derived from a Polyacetylene Core
title_sort elucidation of antimicrobials and biofilm inhibitors derived from a polyacetylene core
topic antibiotics
alkynes
biofilms
structure–activity relationships
Glaser–Hay reaction
url https://www.mdpi.com/1420-3049/29/24/5945
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