Сиросингопин

Description

Syrosingopine is a yohimban alkaloid, a semi-synthetic derivative of reserpine. It differs from the original alkaloid by replacing the trimethoxybenzoyl residue with a syringoyl residue with an ethyl carbonate group, hence the name and synonyms of the type “methyl resernate ester of ethyl carbonate of syringic acid.” It was developed as an antihypertensive agent under the designation Su 3118 and produced under the names Singoserp, Isotens, Raunova, Londomin, Seniramine. The mechanism of hypotensive action is the same as that of reserpine: depletion of peripheral stores of norepinephrine.

Basic Attributes

• CAS No.: 84-36-6
• Chemical formula: C35H42N2O11
• Molecular Weight: 666.71
• Exact weight according to card: 666.71
• EU number: 201-527-0
• UNII:PPG46JF0EG
• NSC number: 77030
• DSSTox ID: DTXSID9023629
• PSA Specs: 144
• XLogP3: 4.63570

Physico-chemical properties

• Density: 1.35 g/cm³
• Melting point: 177 °C
• Boiling point: 795 °C at 760 mm Hg. Art.
• Flash point: 434.6 °C
• Refractive index: 1.615
• Solubility in water: insoluble, 3.1 × 10⁻⁴ g/l at 25 °C

A solubility of 0.00031 g/l with a molecular weight of 667 and a lipophilicity of XLogP3 of 4.64 means almost complete hydrophobicity: working solutions are prepared in dimethyl sulfoxide or ethanol. The exact mass value in the card coincides with the molecular weight and the monoisotopic mass of the formula C35H42N2O11 does not correspond - an artifact of data transfer.

Pharmacological action

The classic direction is to lower blood pressure. Like reserpine, syrosingopine depletes peripheral norepinephrine stores, which weakens sympathetic transmission and decreases vascular tone.

The modern line of research is related to oncology. Syrosingopine was found to be a dual inhibitor of the monocarboxylate lactate transporters MCT1 and MCT4 with IC50 values ​​of 2500 nM and 40 nM, respectively, that is, approximately 60 times more active against MCT4. These proteins remove lactate from the cell along with protons. Their blockade stops the export of lactate, which causes a block in glycolysis, ATP depletion and cell death. Dual inhibition of MCT1 and MCT4 has been shown to be synthetically lethal in combination with metformin due to depletion of the NAD⁺ pool in tumor cells: syrosingopine at a concentration of 5 μM together with metformin suppresses the growth of HL-60 cells. It is noted that the combination enhances the antitumor effect of metformin and phenformin without damaging effects on normal cells.

Toxicity

• LD50 oral, rat: more than 2 g/kg

Scope of application

• research reagent: a tool for blocking lactate transport in cell models
• reference substance in the analysis of rauwolfia alkaloids and their derivatives
• object of research in the field of oncometabolism and combination therapy with biguanides

Safety Information

• Packing level: III
• Hazard category: 6.1(b) - toxic substances
• Transport codes: 1544
• Harmonized phrases H and P, labels and hazard class codes are not given on the card - check with the batch passport

Storage and handling

The product is pharmacologically active and classified as a toxic substance, therefore access to it is limited and separate records are maintained. Store in a tightly closed container, protect from light: yohimban alkaloids are sensitive to light and oxidative destruction. Prepare solutions in organic solvents immediately before the experiment. Carry out work under a hood, wearing gloves and safety glasses, avoiding dust and ingestion. Collect waste and contaminated consumables separately.