TY - JOUR
T1 - Myeloperoxidase inhibitory and antioxidant activities of (E)-2-hydroxy-α-aminocinnamic acids obtained through microwave-assisted synthesis
AU - Rivera-Antonio, Astrid
AU - Rosales-Hernández, Martha Cecilia
AU - Balbuena-Rebolledo, Irving
AU - Santiago-Quintana, José Martín
AU - Mendieta-Wejebe, Jessica Elena
AU - Correa-Basurto, José
AU - García-Vázquez, Juan Benjamín
AU - García-Báez, Efrén Venancio
AU - Padilla-Martínez, Itzia I.
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/6/1
Y1 - 2021/6/1
N2 - Myeloperoxidase (MPO) is an enzyme present in human neutrophils, whose main role is to provide defenses against invading pathogens. However, highly reactive oxygen species (ROS), such as HOCl, are generated from MPO activity, leading to chronic diseases. Herein, we report the microwave-assisted synthesis of a new series of stable (E)-(2-hydroxy)-α-aminocinnamic acids, in good yields, which are structurally analogous to the natural products (Z)-2-hydroxycinnamic acids. The radical scavenging activity (RSA), MPO inhibitory activity and cytotoxicity of the reported compounds were evaluated. The hydroxy derivatives showed the most potent RSA, reducing the presence of DPPH and ABTS radicals by 77% at 0.32 mM and 100% at 0.04 mM, respectively. Their mechanism of action was modeled with BDEOH, IP and ∆EH-L theoretical calculations at the B3LYP/6 − 31 + G(d,p) level. Compounds showed in vitro inhibitory activity of MPO with IC50 values comparable to indomethacin and 5-ASA, but cytotoxicities below 15% at 100–200 µM. Docking calculations revealed that they reach the amino acid residues present in the distal cavity of the MPO active site, where both the amino and carboxylic acid groups of the α-aminopropenoic acid arm are structural requirements for anchoring. (E)-2-hydroxy-α-aminocinnamic acids have been synthesized for the first time with a reliable method and their antioxidant properties demonstrated.
AB - Myeloperoxidase (MPO) is an enzyme present in human neutrophils, whose main role is to provide defenses against invading pathogens. However, highly reactive oxygen species (ROS), such as HOCl, are generated from MPO activity, leading to chronic diseases. Herein, we report the microwave-assisted synthesis of a new series of stable (E)-(2-hydroxy)-α-aminocinnamic acids, in good yields, which are structurally analogous to the natural products (Z)-2-hydroxycinnamic acids. The radical scavenging activity (RSA), MPO inhibitory activity and cytotoxicity of the reported compounds were evaluated. The hydroxy derivatives showed the most potent RSA, reducing the presence of DPPH and ABTS radicals by 77% at 0.32 mM and 100% at 0.04 mM, respectively. Their mechanism of action was modeled with BDEOH, IP and ∆EH-L theoretical calculations at the B3LYP/6 − 31 + G(d,p) level. Compounds showed in vitro inhibitory activity of MPO with IC50 values comparable to indomethacin and 5-ASA, but cytotoxicities below 15% at 100–200 µM. Docking calculations revealed that they reach the amino acid residues present in the distal cavity of the MPO active site, where both the amino and carboxylic acid groups of the α-aminopropenoic acid arm are structural requirements for anchoring. (E)-2-hydroxy-α-aminocinnamic acids have been synthesized for the first time with a reliable method and their antioxidant properties demonstrated.
KW - (E)-dehydro-Phe
KW - (Z)-2-hydroxycinnamic acid
KW - 3-acetamidocoumarins
KW - 3-aminocoumarins
KW - Antioxidants
KW - Hypochlorous acid
UR - http://www.scopus.com/inward/record.url?scp=85107728647&partnerID=8YFLogxK
U2 - 10.3390/ph14060513
DO - 10.3390/ph14060513
M3 - Artículo
C2 - 34071735
AN - SCOPUS:85107728647
SN - 1424-8247
VL - 14
JO - Pharmaceuticals
JF - Pharmaceuticals
IS - 6
M1 - 513
ER -