(-)-Quinine dihydrochloride

Quinine dihydrochloride is an orally active alkaloid extracted from cinchona bark and can be used in anti-malarial studies. Quinine dihydrochloride is a potassium channel inhibitor that inhibits WT mouse Slo3 (KCa5.1) channel currents evoked by voltage pulses to +100 mV with an IC50 of 169 μM[1][2].

Research Areas >> Infection

Signaling Pathways >> Membrane Transporter/Ion Channel >> Potassium Channel

Quinine dihydrochloride (150 μM, 30 min) inhibits the proliferation and cytostatic effects of DENV (Dengue virus) in human hepatocarcinoma HepG2 cell line[1]. Quinine dihydrochloride (37.5-150 μM, 24 hours) significantly reduces viral DENV RNA and protein levels in a dose-dependent manner in human hepatocarcinoma HepG2 cell line [1]. Cell Proliferation Assay[1] Cell Line: Human hepatocarcinoma cell line(HepG2) Concentration: 150 μM Incubation Time: 30 min Result: Inhibited DENV virus replication with 19% yield compared to untreated. Reduced DENV-positive cells from 23.28% to 12.05% in a dose-dependent manner.

Quinine dihydrochloride (oral gavage, 12 or 15 mg/kg, every week, 16 weeks) has some tumor suppressing effect on skin cancer in Swiss albino mice[2]. Quinine dihydrochloride (oral gavage, 10 mg/kg, everyday, 8 weeks) causes a decrease in the antioxidant defense system of rat testicular tissue such as SOD, CAT and GSH enzyme activity in male adult albino rats[3]. Animal Model: Swiss albino mice 7-8-weeks (weighing 24 g)[2] Dosage: 12 mg/kg, 15 mg/kg Administration: Oral gavage; every week; 16 weeks Result: Resulted in a significant reduction in tumor size and weight at 12 mg/kg and little effect at higher dose of 15 mg/kg.

[1]. Shilu Malakar，et al. Drug repurposing of quinine as antiviral against dengue virus infection. Virus Res. 2018 Aug 15;255:171-178. doi: 10.1016/j.virusres.2018.07.018. Epub 2018 Jul 25.

[2]. Jhanwar, Deepika，et al. Chemoprevention of DMBA induced skin carcinogenesis in swiss albino mice by quinine sulfate.(2016): 2636-2640.

[3]. Ebenezer O Farombi, et al. Quercetin protects against testicular toxicity induced by chronic administration of therapeutic dose of quinine sulfate in rats. J Basic Clin Physiol Pharmacol. 2012 Feb 27;23(1):39-44.

MOLECULAR FORMULA :

C20-H24-N2-O2.2Cl-H

MOLECULAR WEIGHT :

397.38

WISWESSER LINE NOTATION :

T66 BNJ HO1 EYQ- DT66 A B CNTJ A1U1 &GH 2

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 :

1392 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

78 mg/kg

TOXIC EFFECTS :

Behavioral - altered sleep time (including change in righting reflex) Behavioral - convulsions or effect on seizure threshold

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

660 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

86 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

641 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

35 mg/kg

TOXIC EFFECTS :

Behavioral - altered sleep time (including change in righting reflex)

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

199 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

57 mg/kg

TOXIC EFFECTS :

Behavioral - altered sleep time (including change in righting reflex) Behavioral - convulsions or effect on seizure threshold

MUTATION DATA

TYPE OF TEST :

Mutation in microorganisms

TEST SYSTEM :

Bacteria - Salmonella typhimurium

DOSE/DURATION :

2800 nmol/plate

REFERENCE :

MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 66,33,1979