Securinine

Names

[ Name ]:
Securinine

[Synonym ]:
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

Biological Activity

[Description]:

(-)-Securinine is plant-derived alkaloid and also a GABAA receptor antagonist.

[Related Catalog]:

Signaling Pathways >> Membrane Transporter/Ion Channel >> GABA Receptor

Signaling Pathways >> Neuronal Signaling >> GABA Receptor

Natural Products >> Alkaloid

Research 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.

[Related Small Molecules]

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

[ 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

Articles

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...

Related Compounds

The content on this webpage is sourced from various professional data sources. If you have any questions or concerns regarding the content, please feel free to contact service1@chemsrc.com.