Quinacrine Dihydrochloride Dihydrate

Names

[ Name ]:
Quinacrine Dihydrochloride Dihydrate

[Synonym ]:
Atebrin hydrochloride
Quinacrinehydrochlorid
MFCD00150069
866 R.P.
Chemiochin
Acrichine
mepacrinehydrochloridedihydrate
atabrinehydrochloridedihydrate
QuinacrineHCl
QUINACRINE,ATABRINE MEPACNINE
Mepacrine dihydrochloride
Chinacrin hydrochloride
hloride2h2-o
ochloride,dihydrate
Mecryl
Erion
Pentilen
mepacrinehcl
N-(6-Chloro-2-methoxy-9-acridinyl)-N,N-diethyl-1,4-pentanediamine dihydrochloride dihydrate
AtabrineMepacnine
QUINACRINE DIHYDROCHLORIDE
Palusan
1,4-Pentanediamine, N-(6-chloro-2-methoxy-9-acridinyl)-N,N-diethyl-, hydrochloride, hydrate (1:2:2)
Crinodora
Akrichin
Italchin
Metochin
Metoquine
Palacrin
69-05-6 {Anhydrous}
Acriquine
Malaricida

Biological Activity

[Description]:

Quinacrine hydrochloride hydrate (Mepacrine hydrochloride hydrate) is an antimalarial agent, which possess anticancer effect both in vitro and vivo. Quinacrine hydrochloride hydrate suppresses NF-κB and activates p53 signaling, which results in the induction of the apoptosis[1].

[Related Catalog]:

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Research Areas >> Infection

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> Autophagy >> Mitophagy

[In Vitro]

Quinacrine (5-20 μM; 24 hours) inhibits the growth of SGC-7901 cells[1]. Quinacrine (7.5 and 15 μM; 24 hours) induces apoptosis in SGC-7901 cells, which is associated with mitochondria-dependent signal pathway and involves p53 upregulation and caspase-3 activation pathway[1]. Quinacrine (15 μM; 24 hours) treatment significantly increased the levels of proapoptotic proteins, including cytochrome c, Bax, and p53, and decreased the levels of antiapoptotic protein Bcl-2, thus shifting the ratio of Bax/Bcl-2 in favor of apoptosis [1]. Cell Viability Assay[1] Cell Line: SGC-7901 cells Concentration: 0, 5, 10, 15, and 20 μM Incubation Time: 24 hours Result: Cell viability was inhibited in a dose-dependent manner, and the mean IC50 value is 16.18 μM. Apoptosis Analysis[1] Cell Line: SGC-7901 cells Concentration: 7.5 and 15 μM Incubation Time: 24 hours Result: The percentage of apoptotic cells, including the early phase and late phase apoptosis, increased to 26.30%, compared with control group of 3.37%. Western Blot Analysis[1] Cell Line: SGC-7901 cells Concentration: 15 μM Incubation Time: 24 hours Result: The relative quantity of cytochrome c protein was upregulated, increased from 0.10 to 0.24. The relative quantity of p53 protein was dramatically increased, from 0.06 to 0.19. The Bax/Bcl-2 ratio was dramatically elevated from 1.21 to 2.59.

[In Vivo]

Quinacrine (100 mg/kg three times per week for two consecutive weeks) significantly suppresses circulating blast cells at days 30/31 and increases the median survival time (MST). Quinacrine does not decrease the body weight of treated animals at the tested dose[2]. Animal Model: Female SCID mice with acute myeloid leukemia (AML)-PS model[2] Dosage: 100 mg/kg Administration: Administered by oral gavage (po); three times a week for two consecutive weeks Result: In the first AML mouse in vivo study, evaluation of circulating leukemic cells detected in blood samples (in percent of white blood cells (WBC)) at day 30/31 showed 72% human tumor cells in the control mice, whereas in mice treated with Quinacrine, this was only 2.2%. The MST of control mice was 34 days whereas it was 46 days in Quinacrine-treated mice.

[References]

[1]. Xiaoyang Wu, et al. Quinacrine Inhibits Cell Growth and Induces Apoptosis in Human Gastric Cancer Cell Line SGC-7901. Curr Ther Res Clin Exp. 2012 Feb;73(1-2):52-64.

[2]. Anna Eriksson, et al. Towards repositioning of quinacrine for treatment of acute myeloid leukemia - Promising synergies and in vivo effects. Leuk Res. 2017 Dec;63:41-46.

Chemical & Physical Properties

[ Boiling Point ]:
557.1ºC at 760 mmHg

[ Melting Point ]:
247 °C

[ Molecular Formula ]:
C₂₃H₃₆Cl₃N₃O₃

[ Molecular Weight ]:
508.909

[ Exact Mass ]:
507.182220

[ PSA ]:
55.85000

[ LogP ]:
7.52080

[ Storage condition ]:
-20℃

[ Water Solubility ]:
2.8 g/100 mL

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: AR7876000

CHEMICAL NAME :: Acridine, 6-chloro-9-((4-(diethylamino)-1-methylbutyl)amino)-2- methoxy-, dihydrochloride, dihydrate

CAS REGISTRY NUMBER :: 6151-30-0

LAST UPDATED :: 199112

DATA ITEMS CITED :: 2

MOLECULAR FORMULA :: C23-H30-Cl-N3-O.2Cl-H.2H2-O

MOLECULAR WEIGHT :: 507.96

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 37 mg/kg

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

REFERENCE :: TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 44,225,1978 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intratesticular

DOSE :: 4 mg/kg

SEX/DURATION :: male 1 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - testes, epididymis, sperm duct

REFERENCE :: CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 6,329,1972

Safety Information

[ Hazard Codes ]:
Xn: Harmful;

[ Risk Phrases ]:
R22;R36/37/38

[ Safety Phrases ]:
S26-S37/39