CAS 5610-40-2|Securinine

Introduction：Basic information about CAS 5610-40-2|Securinine, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. Securinine BiologicalActivity
3. Chemical & Physical Properties
4. Toxicological Information
CHEMICAL IDENTIFICATION
HEALTH HAZARD DATA
ACUTE TOXICITY DATA
5. Safety Information
6. Articles24
7. Synonyms

Common Name	Securinine
CAS Number	5610-40-2	Molecular Weight	217.264
Density	1.3±0.1 g/cm3	Boiling Point	459.0±45.0 °C at 760 mmHg
Molecular Formula	C₁₃H₁₅NO₂	Melting Point	140-142ºC
MSDS	ChineseUSA	Flash Point	197.0±19.6 °C
Symbol	GHS07	Signal Word	Warning

Names

Name	Securinine
Synonym	More Synonyms

Securinine BiologicalActivity

Description	(-)-Securinine is plant-derived alkaloid and also a GABAA receptor antagonist.
Related Catalog	Signaling Pathways >>Membrane Transporter/Ion Channel >>GABA ReceptorSignaling Pathways >>Neuronal Signaling >>GABA ReceptorNatural Products >>AlkaloidResearch Areas >>Neurological Disease
Target	GABAA receptor[1]
In Vitro	(-)-Securinine is a major plant-derived alkaloid and also a GABAA receptor antagonist. (-)-Securinine is significantly potent on HeLa cells growth inhibition with IC50 values of 7.02±0.52 μg/mL (32.3 μM). (-)-Securinine induces apoptosis in a dose-dependent manner in the tested cells, increases the percentage of ROS positive cells and depolarized cells as well as stimulates the activity of ERK1/2, caspase-9 and -3/7. (-)-Securinine also induces cell cycle arrest in S phase. Real-time PCR analysis shows high expression of tumor necrosis factor receptor superfamily (TNFRSF) genes in the cells stimulated with (-)-Securinine[1].
In Vivo	In this tumor model, tumor growth is significantly impaired with (-)-Securinine treatment indicating that (-)-Securinine has potential as an Acute Myeloid Leukemia (AML) therapeutic. (-)-Securinine treated mice (n=5 mice, bilateral tumors), exhibit an average of more than 75% smaller tumors than vehicle treated mice at the end of the study period[2].
Kinase Assay	The cells are seeded in 12-well plates (1×105/well) and treated with (-)-Securinine at concentrations of 1.0 to 50.0 μg/mL. The control cells are exposed to DMSO at a concentration of 0.5% (v/v). After 6 h and 24 h of exposure, the activity of caspase-9 is measured by Caspase-Glo 9 Assay Kit and Glomax Multi+ Detection System, according to the manufacturer’s instruction. The activity of caspase-3/7 is assessed after 24 h of exposure the cells to (-)-Securinine. Then the cells are harvested and prepared using Muse Caspase-3/7 Assay Kit according with the manufacturer’s protocol. The stained cells are analyzed by Muse Cell Analyzer. The experiments are performed at least in three independent repeats[1].
Cell Assay	The viability of the cells is determined by MTT assay. HeLa cells are seeded in 96-well plates at a density of 5×103 cells/well and treated for 24 h with (-)-Securinine in the concentration range of 1.0 to 20.0 μg/mL. The maximal concentrations of the solvents used in all the MTT experiments are 5.0% (v/v) and 1.0% (v/v) for methanol and DMSO, respectively. The absorption of the obtained formazan solution is measured with a plate reader. The viability results are presented as IC50 mean values of at least three independent experiments[1].
Animal Admin	6 week old female nude mice are used and injected bilaterally s.c. with 10×106 HL-60 cells. (-)-Securinine treatment is started 10 days after tumor cell injection. Palpable tumors are present for the established tumor model prior to initiating drug treatment. 15 mg/kg of (-)-Securinine or vehicle (30 µL of DMSO and 70 µL of water) are injected i.p. 2 or 3 times a day for 5 days followed by once a day for two days. This injection schedule is repeated for two additional weeks[2].
References	[1]. Stefanowicz-Hajduk J, et al. Securinine from Phyllanthus glaucus Induces Cell Cycle Arrest and Apoptosis in Human Cervical Cancer HeLa Cells. PLoS One. 2016 Oct 28;11(10):e0165372. [2]. Kalpana Gupta, et al. Securinine, a Myeloid Differentiation Agent with Therapeutic Potential for AML. PLoS One. 2011; 6(6): e21203.

Chemical & Physical Properties

Density	1.3±0.1 g/cm3
Boiling Point	459.0±45.0 °C at 760 mmHg
Melting Point	140-142ºC
Molecular Formula	C₁₃H₁₅NO₂
Molecular Weight	217.264
Flash Point	197.0±19.6 °C
Exact Mass	217.110275
PSA	29.54000
LogP	0.60
Vapour Pressure	0.0±1.1 mmHg at 25°C
Index of Refraction	1.633
InChIKey	SWZMSZQQJRKFBP-WZRBSPASSA-N
SMILES	O=C1C=C2C=CC3CC2(O1)C1CCCCN31
Storage condition	2-8C

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: VS4115000

CHEMICAL NAME :: Securinine, (-)-

CAS REGISTRY NUMBER :: 5610-40-2

LAST UPDATED :: 199201

DATA ITEMS CITED :: 18

MOLECULAR FORMULA :: C13-H15-N-O2

MOLECULAR WEIGHT :: 217.29

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >800 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: CHHTAT Zhonghua Yixue Zazhi. Chinese Medical Journal. (China International Book Trading Corp., POB 2820, Beijing, Peop. Rep. China) V.1- 1915- Suspended 1967-72. Volume(issue)/page/year: 54,234,1974

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 41 mg/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - other changes

REFERENCE :: CHHTAT Zhonghua Yixue Zazhi. Chinese Medical Journal. (China International Book Trading Corp., POB 2820, Beijing, Peop. Rep. China) V.1- 1915- Suspended 1967-72. Volume(issue)/page/year: 54,234,1974

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 15100 ug/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - other changes

REFERENCE :: CHHTAT Zhonghua Yixue Zazhi. Chinese Medical Journal. (China International Book Trading Corp., POB 2820, Beijing, Peop. Rep. China) V.1- 1915- Suspended 1967-72. Volume(issue)/page/year: 54,234,1974

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intramuscular

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 17400 ug/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - other changes

REFERENCE :: CHHTAT Zhonghua Yixue Zazhi. Chinese Medical Journal. (China International Book Trading Corp., POB 2820, Beijing, Peop. Rep. China) V.1- 1915- Suspended 1967-72. Volume(issue)/page/year: 54,234,1974

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Unreported

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 4300 ug/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: YKKZAJ Yakugaku Zasshi. Journal of Pharmacy. (Nippon Yakugakkai, 2-12-15 Shibuya, Shibuya-ku, Tokyo 150, Japan) No.1- 1881- Volume(issue)/page/year: 83,800,1963

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 270 mg/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - other changes

REFERENCE :: CHHTAT Zhonghua Yixue Zazhi. Chinese Medical Journal. (China International Book Trading Corp., POB 2820, Beijing, Peop. Rep. China) V.1- 1915- Suspended 1967-72. Volume(issue)/page/year: 54,234,1974

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 31800 ug/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - other changes

REFERENCE :: CHHTAT Zhonghua Yixue Zazhi. Chinese Medical Journal. (China International Book Trading Corp., POB 2820, Beijing, Peop. Rep. China) V.1- 1915- Suspended 1967-72. Volume(issue)/page/year: 54,234,1974

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 20420 ug/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - other changes

REFERENCE :: CHHTAT Zhonghua Yixue Zazhi. Chinese Medical Journal. (China International Book Trading Corp., POB 2820, Beijing, Peop. Rep. China) V.1- 1915- Suspended 1967-72. Volume(issue)/page/year: 54,234,1974

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 6230 ug/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - other changes

REFERENCE :: CHHTAT Zhonghua Yixue Zazhi. Chinese Medical Journal. (China International Book Trading Corp., POB 2820, Beijing, Peop. Rep. China) V.1- 1915- Suspended 1967-72. Volume(issue)/page/year: 54,234,1974

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intramuscular

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 19320 ug/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - other changes

REFERENCE :: CHHTAT Zhonghua Yixue Zazhi. Chinese Medical Journal. (China International Book Trading Corp., POB 2820, Beijing, Peop. Rep. China) V.1- 1915- Suspended 1967-72. Volume(issue)/page/year: 54,234,1974

TYPE OF TEST :: LD - Lethal dose

ROUTE OF EXPOSURE :: Intramuscular

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: >10 mg/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold

REFERENCE :: CHHTAT Zhonghua Yixue Zazhi. Chinese Medical Journal. (China International Book Trading Corp., POB 2820, Beijing, Peop. Rep. China) V.1- 1915- Suspended 1967-72. Volume(issue)/page/year: 54,234,1974

TYPE OF TEST :: LD - Lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: >54 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: CHHTAT Zhonghua Yixue Zazhi. Chinese Medical Journal. (China International Book Trading Corp., POB 2820, Beijing, Peop. Rep. China) V.1- 1915- Suspended 1967-72. Volume(issue)/page/year: 54,234,1974

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intramuscular

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: 8 mg/kg

TOXIC EFFECTS :: Cardiac - pulse rate increase, without fall in BP Behavioral - convulsions or effect on seizure threshold Gastrointestinal - changes in structure or function of salivary glands

REFERENCE :: CHHTAT Zhonghua Yixue Zazhi. Chinese Medical Journal. (China International Book Trading Corp., POB 2820, Beijing, Peop. Rep. China) V.1- 1915- Suspended 1967-72. Volume(issue)/page/year: 54,234,1974

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - cat

DOSE/DURATION :: 500 mg/kg

TOXIC EFFECTS :: Behavioral - tremor Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - other changes

REFERENCE :: CHHTAT Zhonghua Yixue Zazhi. Chinese Medical Journal. (China International Book Trading Corp., POB 2820, Beijing, Peop. Rep. China) V.1- 1915- Suspended 1967-72. Volume(issue)/page/year: 54,234,1974

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Mammal - cat

DOSE/DURATION :: 10 mg/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Gastrointestinal - changes in structure or function of salivary glands

REFERENCE :: CHHTAT Zhonghua Yixue Zazhi. Chinese Medical Journal. (China International Book Trading Corp., POB 2820, Beijing, Peop. Rep. China) V.1- 1915- Suspended 1967-72. Volume(issue)/page/year: 54,234,1974

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 10 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - miosis (pupillary constriction) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea

REFERENCE :: CHHTAT Zhonghua Yixue Zazhi. Chinese Medical Journal. (China International Book Trading Corp., POB 2820, Beijing, Peop. Rep. China) V.1- 1915- Suspended 1967-72. Volume(issue)/page/year: 54,234,1974

TYPE OF TEST :: LD - Lethal dose

ROUTE OF EXPOSURE :: Unreported

SPECIES OBSERVED :: Amphibian - frog

DOSE/DURATION :: >100 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Ear) - change in acuity Behavioral - somnolence (general depressed activity) Kidney, Ureter, Bladder - other changes

REFERENCE :: CHHTAT Zhonghua Yixue Zazhi. Chinese Medical Journal. (China International Book Trading Corp., POB 2820, Beijing, Peop. Rep. China) V.1- 1915- Suspended 1967-72. Volume(issue)/page/year: 54,234,1974 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 50 mg/kg

SEX/DURATION :: male 5 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count)

REFERENCE :: NATWAY Naturwissenschaften. (Springer-Verlag, Heidelberger Platz 3, D-1000 Berlin 33, Fed. Rep. Ger.) V.1- 1913- Volume(issue)/page/year: 52,483,1965

Safety Information

Symbol	GHS07
Signal Word	Warning
Hazard Statements	H302
Hazard Codes	T: Toxic;
Risk Phrases	R23/24/25
Safety Phrases	36/37/39-45
RIDADR	NONH for all modes of transport
WGK Germany	3
RTECS	VS4115000

Articles24

Proteomic and systems biology analysis of monocytes exposed to securinine, a GABA(A) receptor antagonist and immune adjuvant.

PLoS ONE 7(9) , e41278, (2012)

Securinine, a GABA(A) receptor antagonist, has been reported to enhance monocyte cell killing of Coxiella burnetii without obvious adverse effects in vivo. We employed multiplex 2D gel electrophoresis...

Securinine, a myeloid differentiation agent with therapeutic potential for AML.

PLoS ONE 6(6) , e21203, (2011)

As the defining feature of Acute Myeloid Leukemia (AML) is a maturation arrest, a highly desirable therapeutic strategy is to induce leukemic cell maturation. This therapeutic strategy has the potenti...

L-securinine induced the human colon cancer SW480 cell autophagy and its molecular mechanism.

Fitoterapia 82(8) , 1258-64, (2011)

To investigate the anti-tumor effects of L-securinine inducing colon cancer SW480 cell autophagy and explore its potential molecular mechanism.MTT method was used to detect the antitumor effect of SW4...

Synonyms

1,2,3,4,10,10a-Hexahydro-10-hydroxy

securinine

securinin

Securinan-11-one (9CI)

(1S,2R,8S)-14-Oxa-7-azatetracyclo[6.6.1.0.0]pentadeca-9,11-dien-13-one

8H-6,11b-Methanofuro[2,3-c]pyrido[1,2-a]azepin-2(6H)-one, 9,10,11,11a-tetrahydro-, (6S,11aR,11bS)-

Securan one

(6S,11aR,11bS)-9,10,11,11a-Tetrahydro-8H-6,11b-methanofuro(2,3-c)pyrido(1,2-a)azepin-2(6H)-one

(6S,11aR,11bS)-9,10,11,11a-Tetrahydro-8H-6,11b-methanofuro[2,3-c]-pyrido[1,2-a]azepin-2(6H)-one

SECURAN-11-ONE

Securinan-11-one

Securinan-11-on

(-)-Securinine

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