Dihydrocoumarin

Dihydrocoumarin is a compound found in Melilotus officinalis. Dihydrocoumarin is a yeast Sir2p inhibitor. Dihydrocoumarin also inhibits human SIRT1 and SIRT2 with IC50s of 208 μM and 295 μM, respectively[1].

Signaling Pathways >> Cell Cycle/DNA Damage >> Sirtuin

Signaling Pathways >> Epigenetics >> Sirtuin

Natural Products >> Phenylpropanoids

Research Areas >> Cancer

hSIRT1:208 μM (IC50)

hSIRT2:295 μM (IC50)

Dihydrocoumarin induces a concentration-dependent inhibition of SIRT1 (IC50 of 208 μM) in an in vitro enzymatic assay. A decrease in SIRT1 deacetylase activity is observed even at micromolar doses (85±5.8 and 73±13.7% activity at 1.6 μM and 8 μM, respectively). The microtubule SIRT2 deacetylase is also inhibited with a similar dose dependency (IC50 of 295 μM)[1]. Dihydrocoumarin (1-5 mM) increases cytotoxicity in the TK6 cell line in a dose-dependent manner following a 24-h exposure. Dihydrocoumarin (1-5 mM) increases apoptosis in a dose-dependent manner in the TK6 cell line at the 6-h time point. A 5-mM dose of Dihydrocoumarin increases apoptosis at the 6-h time point in the TK6 cell line[1]. Dihydrocoumarin (1-5 mM) increases p53 lysine 373 and 382 acetylation in a dose-dependent manner in the TK6 cell line following a 24-h exposure period[1].

[1]. Olaharski AJ, et al. The flavoring agent Dihydrocoumarin reverses epigenetic silencing and inhibits sirtuindeacetylases. PLoS Genet. 2005 Dec;1(6):e77.

Selisistat (EX 527) | Nicotinamide | SRT1720 HCl | Sirtinol | 3-TYP | SRT 2104 | Fisetin | OSS_128167 | Thiomyristoyl | Cambinol | Tenovin-1 | CAY10602 | AK-7 | Inauhzin | Tenovin 6 Hydrochloride

DATA ITEMS CITED :

18

MOLECULAR FORMULA :

C9-H8-O2

MOLECULAR WEIGHT :

148.17

WISWESSER LINE NOTATION :

T66 BOVT&J

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

Standard Draize test

ROUTE OF EXPOSURE :

Administration onto the skin

SPECIES OBSERVED :

Rodent - rabbit

REFERENCE :

FCTXAV Food and Cosmetics Toxicology. (London, UK) V.1-19, 1963-81. For publisher information, see FCTOD7. Volume(issue)/page/year: 12,521,1974

TYPE OF TEST :

Standard Draize test

ROUTE OF EXPOSURE :

Administration onto the skin

SPECIES OBSERVED :

Rodent - guinea pig

REFERENCE :

JSCCA5 Journal of the Society of Cosmetic Chemists. (Soc. of Cosmetic Chemists, 1995 Broadway, Suite 1701, New York, NY 10023) V.1- 1947- Volume(issue)/page/year: 28,357,1977 ** ACUTE TOXICITY DATA **

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1460 mg/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity)

REFERENCE :

FCTXAV Food and Cosmetics Toxicology. (London, UK) V.1-19, 1963-81. For publisher information, see FCTOD7. Volume(issue)/page/year: 2,327,1964

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

200 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

NTIS** National Technical Information Service. (Springfield, VA 22161) Formerly U.S. Clearinghouse for Scientific & Technical Information. Volume(issue)/page/year: AD277-689

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Administration onto the skin

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

>5 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

FCTXAV Food and Cosmetics Toxicology. (London, UK) V.1-19, 1963-81. For publisher information, see FCTOD7. Volume(issue)/page/year: 12,521,1974

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

1760 mg/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity)

REFERENCE :

FCTXAV Food and Cosmetics Toxicology. (London, UK) V.1-19, 1963-81. For publisher information, see FCTOD7. Volume(issue)/page/year: 2,327,1964 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

18 gm/kg/16D-I

TOXIC EFFECTS :

Related to Chronic Data - death

REFERENCE :

NTPTR* National Toxicology Program Technical Report Series. (Research Triangle Park, NC 27709) No.206- Volume(issue)/page/year: NTP-TR-423,1993

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

19500 mg/kg/13W-I

TOXIC EFFECTS :

Liver - other changes Blood - changes in erythrocyte (RBC) count Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - true cholinesterase

REFERENCE :

NTPTR* National Toxicology Program Technical Report Series. (Research Triangle Park, NC 27709) No.206- Volume(issue)/page/year: NTP-TR-423,1993

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

27 gm/kg/16D-I

TOXIC EFFECTS :

Related to Chronic Data - death

REFERENCE :

NTPTR* National Toxicology Program Technical Report Series. (Research Triangle Park, NC 27709) No.206- Volume(issue)/page/year: NTP-TR-423,1993

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

104 gm/kg/13W-I

TOXIC EFFECTS :

Liver - changes in liver weight Related to Chronic Data - death

REFERENCE :

NTPTR* National Toxicology Program Technical Report Series. (Research Triangle Park, NC 27709) No.206- Volume(issue)/page/year: NTP-TR-423,1993 ** TUMORIGENIC DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

433 gm/kg/2Y-I

TOXIC EFFECTS :

Tumorigenic - neoplastic by RTECS criteria Kidney, Ureter, Bladder - Kidney tumors

REFERENCE :

NTPTR* National Toxicology Program Technical Report Series. (Research Triangle Park, NC 27709) No.206- Volume(issue)/page/year: NTP-TR-423,1993

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

144 gm/kg/2Y-I

TOXIC EFFECTS :

Tumorigenic - neoplastic by RTECS criteria Liver - tumors

REFERENCE :

NTPTR* National Toxicology Program Technical Report Series. (Research Triangle Park, NC 27709) No.206- Volume(issue)/page/year: NTP-TR-423,1993 *** REVIEWS *** TOXICOLOGY REVIEW PMDCAY Progress in Medical Chemistry. (Elsevier Science Pub. Co., Inc., 52 Vanderbilt Ave., New York, NY 10017) V.1- 1961- Volume(issue)/page/year: 10,85,1974 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOHS - National Occupational Hazard Survey (1974) NOHS Hazard Code - 83169 No. of Facilities: 21 (estimated) No. of Industries: 1 No. of Occupations: 2 No. of Employees: 456 (estimated) NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - 83169 No. of Facilities: 65 (estimated) No. of Industries: 3 No. of Occupations: 8 No. of Employees: 2054 (estimated) No. of Female Employees: 276 (estimated)