TY - JOUR
T1 - Identification of a prenyl chalcone as a competitive lipoxygenase inhibitor
T2 - Screening, biochemical evaluation and molecular modeling studies
AU - Zeraik, Maria Luiza
AU - Pauli, Ivani
AU - Dutra, Luiz A.
AU - Cruz, Raquel S.
AU - Valli, Marilia
AU - Paracatu, Luana C.
AU - de Faria, Carolina M.Q.G.
AU - Ximenes, Valdecir F.
AU - Regasini, Luis O.
AU - Andricopulo, Adriano D.
AU - Bolzani, Vanderlan S.
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/4/2
Y1 - 2021/4/2
N2 - Cyclooxygenase (COX) and lipoxygenase (LOX) are key targets for the development of new anti-inflammatory agents. LOX, which is involved in the biosynthesis of mediators in inflammation and allergic reactions, was selected for a biochemical screening campaign to identify LOX inhibitors by employing the main natural product library of Brazilian biodiversity. Two prenyl chalcones were identified as potent inhibitors of LOX-1 in the screening. The most active compound, (E)-2-O-farnesyl chalcone, decreased the rate of oxygen consumption to an extent similar to that of the positive control, nordihydroguaiaretic acid. Additionally, studies on the mechanism of the action indicated that (E)-2-O-farnesyl chalcone is a competitive LOX-1 inhibitor. Molecular modeling studies indicated the importance of the prenyl moieties for the binding of the inhibitors to the LOX binding site, which is related to their pharmacological properties.
AB - Cyclooxygenase (COX) and lipoxygenase (LOX) are key targets for the development of new anti-inflammatory agents. LOX, which is involved in the biosynthesis of mediators in inflammation and allergic reactions, was selected for a biochemical screening campaign to identify LOX inhibitors by employing the main natural product library of Brazilian biodiversity. Two prenyl chalcones were identified as potent inhibitors of LOX-1 in the screening. The most active compound, (E)-2-O-farnesyl chalcone, decreased the rate of oxygen consumption to an extent similar to that of the positive control, nordihydroguaiaretic acid. Additionally, studies on the mechanism of the action indicated that (E)-2-O-farnesyl chalcone is a competitive LOX-1 inhibitor. Molecular modeling studies indicated the importance of the prenyl moieties for the binding of the inhibitors to the LOX binding site, which is related to their pharmacological properties.
KW - Chalcones
KW - Docking
KW - Inflammation
KW - NuBBE database
UR - http://www.scopus.com/inward/record.url?scp=85105159530&partnerID=8YFLogxK
U2 - 10.3390/molecules26082205
DO - 10.3390/molecules26082205
M3 - Article
C2 - 33921198
AN - SCOPUS:85105159530
SN - 1420-3049
VL - 26
JO - Molecules
JF - Molecules
IS - 8
M1 - 2205
ER -