TY - JOUR
T1 - Synthesis, biological activity and molecular modelling studies of shikimic acid derivatives as inhibitors of the shikimate dehydrogenase enzyme of Escherichia coli
AU - Díaz-Quiroz, Dulce Catalina
AU - Cardona-Félix, César Salvador
AU - Viveros-Ceballos, José Luis
AU - Reyes-González, Miguel Angel
AU - Bolívar, Franciso
AU - Ordoñez, Mario
AU - Escalante, Adelfo
N1 - Publisher Copyright:
© 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Shikimic acid (SA) pathway is the common route used by bacteria, plants, fungi, algae, and certain Apicomplexa parasites for the biosynthesis of aromatic amino acids and other secondary metabolites. As this essential pathway is absent in mammals designing inhibitors against implied enzymes may lead to the development of antimicrobial and herbicidal agents harmless to humans. Shikimate dehydrogenase (SDH) is the fourth enzyme of the SA pathway. In this contribution, a series of SA amide derivatives were synthesised and evaluated for in vitro SDH inhibition and antibacterial activity against Escherichia coli. All tested compounds showed to be mixed type inhibitors; diamide derivatives displayed more inhibitory activity than synthesised monoamides. Among the evaluated compounds, molecules called 4a and 4b were the most active derivatives with IC50 588 and 589 µM, respectively. Molecular modelling studies suggested two different binding modes of monoamide and diamide derivatives to the SDH enzyme of E. coli.
AB - Shikimic acid (SA) pathway is the common route used by bacteria, plants, fungi, algae, and certain Apicomplexa parasites for the biosynthesis of aromatic amino acids and other secondary metabolites. As this essential pathway is absent in mammals designing inhibitors against implied enzymes may lead to the development of antimicrobial and herbicidal agents harmless to humans. Shikimate dehydrogenase (SDH) is the fourth enzyme of the SA pathway. In this contribution, a series of SA amide derivatives were synthesised and evaluated for in vitro SDH inhibition and antibacterial activity against Escherichia coli. All tested compounds showed to be mixed type inhibitors; diamide derivatives displayed more inhibitory activity than synthesised monoamides. Among the evaluated compounds, molecules called 4a and 4b were the most active derivatives with IC50 588 and 589 µM, respectively. Molecular modelling studies suggested two different binding modes of monoamide and diamide derivatives to the SDH enzyme of E. coli.
KW - Escherichia coli
KW - Shikimate dehydrogenase
KW - amide derivative synthesis
KW - enzyme inhibition
KW - molecular docking
KW - shikimic acid
UR - http://www.scopus.com/inward/record.url?scp=85041856736&partnerID=8YFLogxK
U2 - 10.1080/14756366.2017.1422125
DO - 10.1080/14756366.2017.1422125
M3 - Artículo
C2 - 29363372
SN - 1475-6366
VL - 33
SP - 397
EP - 404
JO - Journal of Enzyme Inhibition and Medicinal Chemistry
JF - Journal of Enzyme Inhibition and Medicinal Chemistry
IS - 1
ER -