Sophoridine

Names

[ Name ]:
Sophoridine

[Synonym ]:
1H,5H,10H-Dipyrido[2,1-f:3',2',1'-ij][1,6]naphthyridin-10-one, dodecahydro-, (7aR,13aR,13bR,13cS)-
Allomatrine
(5β)-Matridin-15-one
Bio-0637
5-Epidihydrosophocarpine
Dihydro-5-episophocarpine
(7aR,13aR,13bR,13cS)-Dodecahydro-1H,5H,10H-dipyrido[2,1-f:3',2',1'-ij][1,6]naphthyridin-10-one
sophoridine
matridin-15-one

Biological Activity

[Description]:

Sophoridine is a quinolizidine alkaloid isolated from leafs of Leguminous plant Sophora alopecuroides.L. Sophoridine induces apoptosis. Sophoridine has the potential to be a novel, potent and selective antitumor drug candidate for pancreatic cancer with well-tolerated toxicity[1].

[Related Catalog]:

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

[In Vitro]

Sophoridine (0-500 μM; 48 hours) exhibits remarkable inhibition effects to the growth of human pancreatic, gastric, liver, colon, gallbladder, and prostate carcinoma cells with IC50 values of about 20 μM to 200 μM[1]. Sophoridine (0-20 μM; 48 hours) increases S phase cell population from 26.23% (control) to 38.67% in Miapaca-2 cells and from 29.56% (control) to 39.16% in PANC-1 cells, about a 1.5-fold and a 1.3-fold increase, respectively[1]. Sophoridine (0-20 μM; 48 hours) significantly increases bad and bax levels, and decreases bcl-2 and bcl-xl levels in contrast, with a significant increase in Bax/Bcl-2 ratio[1]. Cell Viability Assay[1] Cell Line: Normal cells: IOSE144, HL-7702 and LO2, BEAS-2B, GES-1, HEK 293 T, HPDE, FHC, Human cancer cells: PANC-1, Mapaca-1, hepG2, SGC-7901, CBC-SD,SGC-996,PC-3,MKN-45,MGC-803,Hela and HCT116 cells Concentration: 0, 3.9, 7.8, 15.5, 31, 62.5, 125, 250, 500 μM Incubation Time: 48 hours Result: Exhibited the most potent cytotoxicity to cancer cells. Cell Cycle Analysis[1] Cell Line: PANC-1 cells; Miapca-2 cells Concentration: 20 μM Incubation Time: 48 hours Result: Led to accumulated population in the S phase. Western Blot Analysis[1] Cell Line: PANC-1 cells; Miapca-2 cells Concentration: 20 μM Incubation Time: 48 hours Result: Induced the activation of intrinsic apoptosis pathway.

[In Vivo]

Sophoridine (intraperitoneal injection; 20 or 40 mg/kg; 21 days) can inhibit the growth of xenograft pancreatic tumors[1]. Animal Model: BALB/c homozygous (nu/nu) nude mice[1] Dosage: 20 or 40 mg/kg Administration: Intraperitoneal injection; 20 or 40 mg/kg; 21 days Result: Decreased xenograft pancreatic tumors mass.

[References]

[1]. Xu Z, et al. Sophoridine induces apoptosis and S phase arrest via ROS-dependent JNK and ERK activation in human pancreatic cancer cells. J Exp Clin Cancer Res. 2017 Sep 11;36(1):124.

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Boiling Point ]:
396.7±31.0 °C at 760 mmHg

[ Melting Point ]:
109 °C

[ Molecular Formula ]:
C₁₅H₂₄N₂O

[ Molecular Weight ]:
248.364

[ Flash Point ]:
172.7±17.2 °C

[ Exact Mass ]:
248.188858

[ PSA ]:
23.55000

[ LogP ]:
1.44

[ Vapour Pressure ]:
0.0±0.9 mmHg at 25°C

[ Index of Refraction ]:
1.581

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: WG1250000

CHEMICAL NAME :: Sophoridine

CAS REGISTRY NUMBER :: 6882-68-4

LAST UPDATED :: 199412

DATA ITEMS CITED :: 4

MOLECULAR FORMULA :: C15-H24-N2-O

MOLECULAR WEIGHT :: 248.41

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 243 mg/kg

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

REFERENCE :: ZYZAEU Zhongguo Yaoxue Zazhi. Chinese Pharmacuetical Journal. (China International Book Trading Corp., POB 2820, Beijing, Peop. China) V.24- 1989- Volume(issue)/page/year: 27,201,1992

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 64300 ug/kg

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

REFERENCE :: CYLPDN Zhongguo Yaoli Xuebao. Acta Pharmacologica Sinica. Chinese Journal of Pharmacology. (China International Book Trading Corp., POB 2820, Beijing, Peop. Rep. China) V.1- 1980- Volume(issue)/page/year: 8,153,1987

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 46800 ug/kg

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

REFERENCE :: YFZADL Yaowu Fenxi Zazhi. Journal of Pharmaceutical Analysis. (China International Book Trading Corp., POB 2820, Beijing, Peop. Rep. China) V.1- 1981- Volume(issue)/page/year: 6,96,1986 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 350 mg/kg/35D-I

TOXIC EFFECTS :: Blood - changes in leukocyte (WBC) count

REFERENCE :: CYLPDN Zhongguo Yaoli Xuebao. Acta Pharmacologica Sinica. Chinese Journal of Pharmacology. (China International Book Trading Corp., POB 2820, Beijing, Peop. Rep. China) V.1- 1980- Volume(issue)/page/year: 8,153,1987

Safety Information

[ Hazard Codes ]:
Xi

[ Safety Phrases ]:
24/25