2,2'-Dithiobis(pyridine-N-oxide)

Dipyrithione is a potent antimicrobial agent. Dipyrithione shows antifungal activity and antiproliferative activity. Dipyrithione induces apoptosis and cycle arrest at G1 phase. Dipyrithione shows anti-inflammatory activity in vivo. Dipyrithione shows anti-tumor activity. Dipyrithione has the potential for the research of dermatophytosis[1][2][3].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Research Areas >> Infection

Signaling Pathways >> Anti-infection >> Fungal

Research Areas >> Inflammation/Immunology

Signaling Pathways >> Anti-infection >> Bacterial

Dipyrithione (20 μg/mL) shows antifungal activity with MIC values of 6.03 µM for Trichophyton rubrum[1]. Dipyrithione (72 h) shows cytotoxic activity against 293 T cells with an IC50 value of 0.22 µM[1]. Dipyrithione (1-5 µM; 8.5 h) inhibits LPS (100 ng/ml)-induced up-regulation of iNOS and COX-2 in RAW264.7 cells in a dose-dependent manner[2]. Dipyrithione (1 µM; 8.5 h) suppresses LPS-induced increase of iNOS but not COX-2 mRNA level, inhibits LPS-increased NO production[2]. Dipyrithione (3 µM; 2, 5 h) decreases phosphorylation of STAT1 induced by LPS and does not influence LPS-induced MAPK and NF-κB activation in RAW 246.7 cells[2]. Dipyrithione (0-5 μg/mL; 48 h) shows antiproliferative activity for KB, 231, U937 and K562 cells in a dose dependent manner[3]. Dipyrithione (2.5 μg/ml) induces apoptosis and cycle arrest at G1 phase[3]. Western Blot Analysis[2] Cell Line: RAW264.7 cells Concentration: 1-5 µM Incubation Time: 8.5 h Result: Inhibited the expression of LPS (100 ng/ml)-induced up-regulation of iNOS and COX-2 in a dose-dependent manner. Cell Proliferation Assay[2] Cell Line: KB, 231, U937, K562 cells Concentration: 2.5 μg/ml Incubation Time: 24 h Result: Induced cell cycle arrest at G1 phase with induced p21 accumulation, CyclinD1 and CyclinE1 expressions were downregulated. Apoptosis Analysis[3] Cell Line: KB, 231, U937, K562 cells Concentration: 2.5 μg/ml Incubation Time: 36 h Result: Induced apoptosis by induced cleavage of caspase-9, caspase-3 and PARP. Western Blot Analysis[3] Cell Line: RAW264.7 cells Concentration: 1-5 µM Incubation Time: 8.5 h Result: Inhibited the expression of LPS (100 ng/ml)-induced up-regulation of iNOS and COX-2 in a dose-dependent manner.

Dipyrithione (0.2 mg/cm2; externally once daily for 10 days) shows great anti-dermatophyte activity effects in guinea pig[1]. Dipyrithione (1, 2.5, 5 mg/kg; i.p.) shows anti-inflammatory activity in mouse[2].Dipyrithione (5 mg/kg; i.p.; daily for 10 days) shows anti-tumor acyivity in mouse[3]. Animal Model: Guinea pig (infected with Trichophyton rubrum)[1] Dosage: 0.2 mg/cm2 Administration: Externally once daily for 10 days Result: Showed normal hair growth, with no scaly skin. Animal Model: 18-22g male ICR mice2 Dosage: 1, 2.5, 5 mg/kg Administration: I.p. Result: Raised the survival rate from 10% to 30%, 60% and 90%, respectively. Animal Model: 6 weeks, 18-20 g male ICR mice (hepatoma 22 (H22) cells)[3] Dosage: 2.5 mg/kg Administration: I.p.; daily for 10 days Result: Inhibited the growth of tumor.

[1]. Song X, et al. In vivo antifungal activity of dipyrithione against Trichophyton rubrum on guinea pig dermatophytosis models. Biomed Pharmacother. 2018 Dec;108:558-564.

[2]. Liu Z, et al. Dipyrithione inhibits lipopolysaccharide-induced iNOS and COX-2 up-regulation in macrophages and protects against endotoxic shock in mice. FEBS Lett. 2008 May 28;582(12):1643-50.

[3]. Fan Y, et al. Dipyrithione induces cell-cycle arrest and apoptosis in four cancer cell lines in vitro and inhibits tumor growth in a mouse model. BMC Pharmacol Toxicol. 2013 Oct 21;14:54.

DATA ITEMS CITED :

6

MOLECULAR FORMULA :

C10-H8-N2-O2-S2

MOLECULAR WEIGHT :

252.32

WISWESSER LINE NOTATION :

T6NJ AO BSS- BT6NJ AO

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

Standard Draize test

ROUTE OF EXPOSURE :

Administration into the eye

SPECIES OBSERVED :

Rodent - rabbit

REFERENCE :

NTIS** National Technical Information Service. (Springfield, VA 22161) Formerly U.S. Clearinghouse for Scientific & Technical Information. Volume(issue)/page/year: OTS0535316 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

5280 ug/kg

SEX/DURATION :

female 16 day(s) pre-mating female 1-6 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - other measures of fertility

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 15,947,1978

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

1600 ug/kg

SEX/DURATION :

female 6-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Effects on Newborn - behavioral

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 15,1169,1978

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

1344 ug/kg

SEX/DURATION :

female 15-21 day(s) after conception lactating female 21 day(s) post-birth

TOXIC EFFECTS :

Reproductive - Effects on Newborn - behavioral Reproductive - Effects on Newborn - physical

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 16,131,1978