Design and Properties of New Multi-target Michael Acceptors

a 2024

Design and Properties of New Multi-target Michael Acceptors

JAMPÍLEK, Jsoef; Tomáš STRHÁRSKY; Lucia VRÁBLOVÁ; Dominika KOS; Tomáš GONĚC et al.

Základní údaje

Originální název

Design and Properties of New Multi-target Michael Acceptors

Autoři

JAMPÍLEK, Jsoef; Tomáš STRHÁRSKY; Lucia VRÁBLOVÁ; Dominika KOS ; Tomáš GONĚC a Jiří KOS

Vydání

Novel Trends in Chemistry, Research and Education 2024, 2024

Další údaje

Jazyk

angličtina

Typ výsledku

Konferenční abstrakt

Obor

30107 Medicinal chemistry

Stát vydavatele

Slovensko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/24:00137891

Organizační jednotka

Lékařská fakulta

ISBN

978-80-574-0370-8

DOI

https://doi.org/10.33542/NTI-0370-8

Klíčová slova anglicky

Multi-target; Michael Acceptors; Azanaphthalene Bioisosteres

Změněno: 5. 12. 2024 14:16, doc. PharmDr. Jiří Kos, Ph.D.

Anotace

V originále

Increasing microbial burden and the development of antimicrobial resistance (AMR) pose a major threat to human health worldwide. In addition to the increased risk of patient death, AMR represents a longer hospital stay and increased health care costs. This state of affairs is extremely undesirable and, apart from various approaches , it is of course most advantageous to design new entities with a new/innovative mechanism of action. One possibility for the design of new drugs is inspiration from natural compounds with multiple activities. Our team specializes in the investigations of multi-target anti-invasive agents based on ring-substituted azanaphthalene bioisosteres; such as hydroxynaphthanilides with activity against Gram-positive bacteria and mycobacteria. Modifications to increase solubility led to the removal of one ring, resulting in the (E)-prop-1-en-1-ylbenzene scaffold. A number of different ring-substituted anilides were designed, prepared and tested. Moieties with electron-withdrawing properties were chosen as substituents of the anilide ring. These designed agents meet the definition of so-called Michael acceptors, i.e. compounds in which double/triple bonds are conjugated with electron-withdrawing groups and which are able to react with nucleophiles, i.e., electron-rich substrates, and thus have the ability to interact with many biological targets. This contribution focuses on the design, biological investigations and discussion of structure-activity relationships within several series of new amides.

Citovat

JAMPÍLEK, Jsoef; Tomáš STRHÁRSKY; Lucia VRÁBLOVÁ; Dominika KOS; Tomáš GONĚC a Jiří KOS. Design and Properties of New Multi-target Michael Acceptors. In Novel Trends in Chemistry, Research and Education 2024. 2024. ISBN 978-80-574-0370-8. Dostupné z: https://doi.org/10.33542/NTI-0370-8.

@proceedings{2457623,
   author = {Jampílek, Jsoef and Strhársky, Tomáš and Vráblová, Lucia and Kos, Dominika and Goněc, Tomáš and Kos, Jiří},
   booktitle = {Novel Trends in Chemistry, Research and Education 2024},
   doi = {https://doi.org/10.33542/NTI-0370-8},
   keywords = {Multi-target; Michael Acceptors; Azanaphthalene Bioisosteres},
   language = {eng},
   isbn = {978-80-574-0370-8},
   title = {Design and Properties of New Multi-target Michael Acceptors},
   url = {https://zenodo.org/records/14259662},
   year = {2024}
}

TY  - CONF
ID  - 2457623
AU  - Jampílek, Jsoef - Strhársky, Tomáš - Vráblová, Lucia - Kos, Dominika - Goněc, Tomáš - Kos, Jiří
PY  - 2024
TI  - Design and Properties of New Multi-target Michael Acceptors
SN  - 9788057403708
KW  - Multi-target
KW  - Michael Acceptors
KW  - Azanaphthalene Bioisosteres
UR  - https://zenodo.org/records/14259662
N2  - Increasing microbial burden and the development of antimicrobial resistance (AMR) pose a major threat to human health worldwide. In addition to the increased risk of patient death, AMR represents a longer hospital stay and increased health care costs. This state of affairs is extremely undesirable and, apart from various approaches , it is of course most advantageous to design new entities with a new/innovative mechanism of action. One possibility for the design of new drugs is inspiration from natural compounds with multiple activities. Our team specializes in the investigations of multi-target anti-invasive agents based on ring-substituted azanaphthalene bioisosteres; such as hydroxynaphthanilides with activity against Gram-positive bacteria and mycobacteria. Modifications to increase solubility led to the removal of one ring, resulting in the (E)-prop-1-en-1-ylbenzene scaffold. A number of different ring-substituted anilides were designed, prepared and tested. Moieties with electron-withdrawing properties were chosen as substituents of the anilide ring. These designed agents meet the definition of so-called Michael acceptors, i.e. compounds in which double/triple bonds are conjugated with electron-withdrawing groups and which are able to react with nucleophiles, i.e., electron-rich substrates, and thus have the ability to interact with many biological targets. This contribution focuses on the design, biological investigations and discussion of structure-activity relationships within several series of new amides.
ER  -

JAMPÍLEK, Jsoef; Tomáš STRHÁRSKY; Lucia VRÁBLOVÁ; Dominika KOS; Tomáš GONĚC a Jiří KOS. Design and Properties of New Multi-target Michael Acceptors. In \textit{Novel Trends in Chemistry, Research and Education 2024}. 2024. ISBN~978-80-574-0370-8. Dostupné z: https://doi.org/10.33542/NTI-0370-8.

Přehled o publikaci