U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C22H28N2O4
Molecular Weight 384.4696
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of ISORHYNCHOPHYLLINE

SMILES

CC[C@@]1([H])CN2CC[C@]3(c4ccccc4N=C3O)[C@]2([H])C[C@]1([H])/C(=C(/[H])\OC)/C(=O)OC

InChI

InChIKey=DAXYUDFNWXHGBE-VKCGGMIFSA-N
InChI=1S/C22H28N2O4/c1-4-14-12-24-10-9-22(17-7-5-6-8-18(17)23-21(22)26)19(24)11-15(14)16(13-27-2)20(25)28-3/h5-8,13-15,19H,4,9-12H2,1-3H3,(H,23,26)/b16-13+/t14-,15-,19-,22-/m0/s1

HIDE SMILES / InChI

Molecular Formula C22H28N2O4
Molecular Weight 384.4696
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 4 / 4
E/Z Centers 1
Optical Activity UNSPECIFIED

Description
Curator's Comment:: https://www.ncbi.nlm.nih.gov/pubmed/12546715 | https://www.ncbi.nlm.nih.gov/pubmed/28534824 | https://www.ncbi.nlm.nih.gov/pubmed/27561181

Isorhynchophylline is a plant alkaloid isolated from Uncaria species with therapeutic potential for cardiovascular and central nervous system diseases. The antihypertensive effect of isorhynchophylline was firstly observed in 1989, which was strongly linked to the traditional use of Uncaria species (Gouteng in Chinese). Isorhynchophylline and rhynchophylline were the main hypotensive constituents in Uncaria rhynchophylla. In rat isolated mesenteric arteries and tail artery, isorhynchophylline inhibited the increased infusion pressure induced by high K+ and norepinephrine in a concentration-dependent manner. The potency of isorhynchophylline and rhynchophylline was similar in mesenteric arteries, but in the tail artery, the effect of isorhynchophylline on high K+ induced infusion pressure increase was stronger than that of rhynchophylline, and there was a similar trend in the contractile response induced by norepinephrine. Isorhynchophylline also inhibited the hypertensive effect of angiotensin II. The results indicate that in small blood vessels of rat, isorhynchophylline can directly inhibit the contractile responses induced by several agonists. In vivo, ouabain and CaCl2 were used to establish experimental arrhythmic models in guinea pigs and rats. In vitro, the whole-cell patch-clamp technique was used to study the effect of isorhynchophylline on action potential duration and calcium channels in acutely isolated guinea pig and rat cardiomyocytes. Isorhynchophylline, infusion 0–16 mg/kg at a constant rate, dose-dependently decreased heart rate, prolonged sinus node recovery time, and PR, AH, HV intervals. Isorhynchophylline significantly inhibited the heart rate and atrioventricular conduction. These inhibitory effects of isorhynchophylline were partially antagonized by isoprenaline, but not by atropine. Isorhynchophylline inhibited the automaticity and contractile force of isolated guinea pig atrium in a concentration-dependent manner. Isorhynchophylline significantly depressed adrenaline-induced automaticity, and prolonged functional refractory period and decreased excitability. Furthermore, 10 μmol/L of isorhynchophylline reduced the effect of ouabain on the contractile force in the left atrium and significantly inhibited the response to paired stimulation. In anesthetized dogs, isorhynchophylline markedly reduced the tension-time index which indicated myocardial oxygen consumption. The result indicates that the decrease of myocardial oxygen consumption by isorhynchophylline would protect the heart against ischemia induced by hypertension. Isorhynchophylline showed a mild central depressive effect in mice. Isorhynchophylline significantly decreased locomotor activity after oral administration to mice. The depression of locomotor activity upon administration of the alkaloid appears to be due to mediating of the central dopaminergic system. Isorhynchophylline dose-dependently inhibited 5-hydroxytryptamine (5-HT)2A receptor-mediated head-twitch but not 5-HT1A receptor-mediated head-weaving responses evoked by 5-methoxy-N, N-dimethyltryptamine. Isorhynchophylline attenuated the in vitro ischemia-induced neuronal damage in a dose-dependent manner. Isorhynchophylline protects against glutamate-induced neuronal death in cultured cerebellar granule cells by inhibition of Ca2+ influx. Pretreatment with isorhynchophylline significantly elevated cell viability, decreased the levels of intracellular reactive oxygen species and malondialdehyde, increased the level of glutathione, and stabilized mitochondrial membrane potential in β- amyloid(25–35)-induced neurotoxicity in rat pheochromocytoma cells. In unthoracotomized dogs, isorhynchophylline (5 mg/kg, iv) reduced the mean arterial pressure but did not affect renal blood flow. Isorhynchophylline did not block nictitating membrane contraction induced by stimulating collum sympathetic nerve and did not decrease blood pressure after injected in the cerebral ventricle.

Approval Year

PubMed

PubMed

TitleDatePubMed
Patents

Patents

Sample Use Guides

5mg/kg
Route of Administration: Intravenous
Five human cancer cell lines, human myeloid leukemia HL-60, lung cancer A549, hepatocellular carcinoma SMMC-7721, breast cancer MCF-7, and colon cancer SW480 cells, were used in the cytotoxic assay. Cells were cultured in RPMI-1640 or in DMEM medium (Hyclone, USA), supplemented with 10% fetal bovine serum (Hyclone, USA) in 5% CO2 at 37 C. The cytotoxicity assay was performed according to the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) method in 96-well microplates. 100 μL of adherent cells was seeded into each well of 96-well cell culture plates and allowed to adhere for 12 h before addition of Isorhynchophylline, while suspended cells were seeded just before drug addition with initial density of 1 x 10^5 cells/mL. Each tumor cell line was exposed to the test compound at concentrations of 0.0625, 0.32, 1.6, 8, and 40 μM in triplicates for 48 h, with cisplatin (Sigma, USA) as a positive control. After compound treatment, cell viability was detected and a cell growth curve was graphed.
Substance Class Chemical
Created
by admin
on Sat Jun 26 14:29:23 UTC 2021
Edited
by admin
on Sat Jun 26 14:29:23 UTC 2021
Record UNII
7F4P99KHLJ
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ISORHYNCHOPHYLLINE
Common Name English
ISORHYNCHOPHYLLINE (CONSTITUENT OF CAT'S CLAW) [DSC]
Common Name English
CORYNOXAN-16-CARBOXYLIC ACID, 16,17-DIDEHYDRO-17-METHOXY-2-OXO-, METHYL ESTER, (16E,20.ALPHA.)-
Common Name English
7-ISORHYNCOPHYLLINE
Common Name English
SPIRO(3H-INDOLE-3,1'(5'H)-INDOLIZINE)-7'-ACETIC ACID, 6'-ETHYL-1,2,2',3',6',7',8',8'A-OCTAHYDRO-.ALPHA.-(METHOXYMETHYLENE)-2-OXO-, METHYL ESTER, (.ALPHA.E,1'S,6'R,7'S,8'AS)-
Systematic Name English
Code System Code Type Description
CAS
6859-01-4
Created by admin on Sat Jun 26 14:29:23 UTC 2021 , Edited by admin on Sat Jun 26 14:29:23 UTC 2021
PRIMARY
FDA UNII
7F4P99KHLJ
Created by admin on Sat Jun 26 14:29:23 UTC 2021 , Edited by admin on Sat Jun 26 14:29:23 UTC 2021
PRIMARY
PUBCHEM
3037048
Created by admin on Sat Jun 26 14:29:23 UTC 2021 , Edited by admin on Sat Jun 26 14:29:23 UTC 2021
PRIMARY
Related Record Type Details
CONSTITUENT ALWAYS PRESENT -> PARENT
PARENT -> CONSTITUENT ALWAYS PRESENT
Constituent of Uncaria tomentosa stem?s inner bark of Uncaria tomentosa stem.