np9b00418_si_001.pdf (2.48 MB)
Synthesis, Purification, and Selective β2‑AR Agonist and Bronchodilatory Effects of Catecholic Tetrahydroisoquinolines from Portulaca oleracea
journal contribution
posted on 2019-10-18, 12:38 authored by Er-Lan Yang, Bin Sun, Zi-Yi Huang, Jian-Guang Lin, Bo Jiao, Lan XiangA green, biomimetic, phosphate-mediated
Pictet–Spengler
reaction was used in the synthesis of three catecholic tetrahydroisoquinolines, 1, 2, and 12, present in the medicinal
plant Portulaca oleracea, as well as their analogues 3–11, 13, and 14, with dopamine hydrochloride and aldehydes as the substrates. AB-8
macroporous resin column chromatography was applied for purification
of the products from the one-step high-efficacy synthesis. It eliminated
the difficulties in the isolation of catecholic tetrahydroisoquinolines
from the aqueous reaction system and unreacted dopamine hydrochloride.
Activity screening in CHO-K1/Gα15 cell models consistently expressing
α1B-, β1-, or β2-adrenergic receptors indicated that 12 and 2, compounds that are present in P. oleracea, possessed
the most potent β2-adrenergic receptor agonist activity
and 2 was a selective β2-adrenergic
receptor agonist at the concentration of 100 μM. Both 12 and 2 exhibited dose-dependent bronchodilator
effects on the histamine-induced contraction of isolated guinea-pig
tracheal smooth muscle, with EC50 values of 0.8 and 2.8
μM, respectively. These findings explain the scientific rationale
of P. oleracea use as an antiasthmatic herb in folk
medicine and provide the basis for the discovery of novel antiasthma
drugs.
History
Usage metrics
Categories
Keywords
dose-dependent bronchodilator effectscatecholic tetrahydroisoquinolinesnovel antiasthma drugsEC 50 values100 μ Mplant Portulaca oleraceaadrenergic receptor agonist activityab -8 macroporous resin column chromatographyCHO-Kunreacted dopamine hydrochloridesynthesis2.8 μ Mβ 2adrenergic receptor agonistAR
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC