MRSA pyruvate kinase inhibitory activity of synthetically derived thiazole containing deoxytopsentin analogues
- Veale, Clinton G L, Zoraghi, Roya, Lobb, Kevin A, Reiner, Neil E, Andersen, Raymond J, Davies-Coleman, Michael T
- Authors: Veale, Clinton G L , Zoraghi, Roya , Lobb, Kevin A , Reiner, Neil E , Andersen, Raymond J , Davies-Coleman, Michael T
- Date: 2014
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/448923 , vital:74771 , xlink:href="https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0034-1382365"
- Description: The health care crisis caused by methicillin resistant Staphylococcus aureus (MRSA) is due in part to a lack of fundamental drug discovery research into new antibiotics with novel modes of action. Marine bis-indole alkaloids have proved to be effective in vitro antibacterials. We present the synthesis of thiazole containing analogues of the marine natural product MRSA pyruvate kinase (PK) inhibitor, 6-bromodeoxytopsenin. The synthetic analogues showed moderate activity compared to the marine natural product against MRSA PK, an evolutionary conserved hub protein critical for bacterial survival. Our synthesis, via a Hantzsch thiazole condensation of α-oxo-1H-indole-3-thioacetamides with 2-bromo-1-(1H-indol-3-yl)-ethanones provided several challenges.
- Full Text:
- Date Issued: 2014
- Authors: Veale, Clinton G L , Zoraghi, Roya , Lobb, Kevin A , Reiner, Neil E , Andersen, Raymond J , Davies-Coleman, Michael T
- Date: 2014
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/448923 , vital:74771 , xlink:href="https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0034-1382365"
- Description: The health care crisis caused by methicillin resistant Staphylococcus aureus (MRSA) is due in part to a lack of fundamental drug discovery research into new antibiotics with novel modes of action. Marine bis-indole alkaloids have proved to be effective in vitro antibacterials. We present the synthesis of thiazole containing analogues of the marine natural product MRSA pyruvate kinase (PK) inhibitor, 6-bromodeoxytopsenin. The synthetic analogues showed moderate activity compared to the marine natural product against MRSA PK, an evolutionary conserved hub protein critical for bacterial survival. Our synthesis, via a Hantzsch thiazole condensation of α-oxo-1H-indole-3-thioacetamides with 2-bromo-1-(1H-indol-3-yl)-ethanones provided several challenges.
- Full Text:
- Date Issued: 2014
Synthesis and MRSA PK inhibitory activity of thiazole containing deoxytopsentin analogues
- Veale, Clinton G L, Lobb, Kevin A, Zoraghi, Roya, Morrison, James P, Reiner, Neil E, Andersen, Raymond J, Davies-Coleman, Michael T
- Authors: Veale, Clinton G L , Lobb, Kevin A , Zoraghi, Roya , Morrison, James P , Reiner, Neil E , Andersen, Raymond J , Davies-Coleman, Michael T
- Date: 2014
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/448028 , vital:74692 , xlink:href="https://doi.org/10.1016/j.tet.2014.09.007"
- Description: The public health care crisis caused by the emergence of drug resistant bacterial strains, e.g., methicillin resistant Staphylococcus aureus (MRSA) has underlined the urgent need to accelerate the discovery of new chemical entities active against antibiotic resistant bacteria. We report here the synthesis of a series thiazole containing deoxytopsentin analogues, which show moderate activity against a target MRSA pyruvate kinase enzyme: an evolutionary conserved hub protein critical for bacterial survival. A Hantzsch thiazole coupling between a-oxo-1H-indole-3-thioacetamides and 2-bromo-1-(1H-indol-3-yl)-ethanones provided facile access to the thiazole containing deoxytopsentin compounds.
- Full Text:
- Date Issued: 2014
- Authors: Veale, Clinton G L , Lobb, Kevin A , Zoraghi, Roya , Morrison, James P , Reiner, Neil E , Andersen, Raymond J , Davies-Coleman, Michael T
- Date: 2014
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/448028 , vital:74692 , xlink:href="https://doi.org/10.1016/j.tet.2014.09.007"
- Description: The public health care crisis caused by the emergence of drug resistant bacterial strains, e.g., methicillin resistant Staphylococcus aureus (MRSA) has underlined the urgent need to accelerate the discovery of new chemical entities active against antibiotic resistant bacteria. We report here the synthesis of a series thiazole containing deoxytopsentin analogues, which show moderate activity against a target MRSA pyruvate kinase enzyme: an evolutionary conserved hub protein critical for bacterial survival. A Hantzsch thiazole coupling between a-oxo-1H-indole-3-thioacetamides and 2-bromo-1-(1H-indol-3-yl)-ethanones provided facile access to the thiazole containing deoxytopsentin compounds.
- Full Text:
- Date Issued: 2014
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