TY - JOUR
T1 - Interactions of a boron-containing levodopa derivative on D2 dopamine receptor and its effects in a Parkinson disease model
AU - Abad-García, Antonio
AU - Ocampo-Néstor, A. Lilia
AU - Das, Bhaskar C.
AU - Farfán-García, Eunice D.
AU - Bello, Martiniano
AU - Trujillo-Ferrara, José G.
AU - Soriano-Ursúa, Marvin A.
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Society for Biological Inorganic Chemistry (SBIC).
PY - 2022/2
Y1 - 2022/2
N2 - Levodopa is a cornerstone in Parkinson’s disease treatment. Beneficial effects are mainly by binding on D2 receptors. Docking simulations of a set of compounds including well-known D2-ligands and a pool of Boron-Containing Compounds (BCC), particularly boroxazolidones with a tri/tetra-coordinated boron atom, were performed on the D2 Dopamine receptor (D2DR). Theoretical results yielded higher affinity of the compound DPBX, a Dopaboroxazolidone, than levodopa on D2DR. Essential interactions with residues in the third and sixth transmembrane domains of the D2DR appear to be crucial to induce and stabilize interactions in the active receptor state. Results from a motor performance evaluation of a murine model of Parkinson’s disease agree with theoretical results, as DPBX showed similar efficacy to that of levodopa for diminishing MPTP-induced parkinsonism. This beneficial effect was disrupted with prior Risperidone (D2DR antagonist) administration, supporting the role of D2DR in the biological effect of DPBX. In addition, DPBX limited neuronal loss in substantia nigra in a similar manner to that of levodopa administration. Graphical abstract: [Figure not available: see fulltext.]
AB - Levodopa is a cornerstone in Parkinson’s disease treatment. Beneficial effects are mainly by binding on D2 receptors. Docking simulations of a set of compounds including well-known D2-ligands and a pool of Boron-Containing Compounds (BCC), particularly boroxazolidones with a tri/tetra-coordinated boron atom, were performed on the D2 Dopamine receptor (D2DR). Theoretical results yielded higher affinity of the compound DPBX, a Dopaboroxazolidone, than levodopa on D2DR. Essential interactions with residues in the third and sixth transmembrane domains of the D2DR appear to be crucial to induce and stabilize interactions in the active receptor state. Results from a motor performance evaluation of a murine model of Parkinson’s disease agree with theoretical results, as DPBX showed similar efficacy to that of levodopa for diminishing MPTP-induced parkinsonism. This beneficial effect was disrupted with prior Risperidone (D2DR antagonist) administration, supporting the role of D2DR in the biological effect of DPBX. In addition, DPBX limited neuronal loss in substantia nigra in a similar manner to that of levodopa administration. Graphical abstract: [Figure not available: see fulltext.]
KW - Boron
KW - Boroxazolidone
KW - Levodopa
KW - MPTP
KW - Parkinson
UR - http://www.scopus.com/inward/record.url?scp=85119609818&partnerID=8YFLogxK
U2 - 10.1007/s00775-021-01915-2
DO - 10.1007/s00775-021-01915-2
M3 - Artículo
C2 - 34806120
AN - SCOPUS:85119609818
SN - 0949-8257
VL - 27
SP - 121
EP - 131
JO - Journal of Biological Inorganic Chemistry
JF - Journal of Biological Inorganic Chemistry
IS - 1
ER -