riddelliine: structure [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]
riddelliine : A macrodiolide that is 13,19-didehydrosenecionan bearing two additional hydroxy substituents at positions 12 and 18 as well as two additional oxo groups at positions 11 and 16. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]
| ID Source | ID |
|---|---|
| PubMed CID | 5281744 |
| CHEBI ID | 63924 |
| SCHEMBL ID | 20771236 |
| MeSH ID | M0061618 |
| Synonym |
|---|
| (15z)-12,18-dihydroxy-13,19-didehydrosenecionan-11,16-dione |
| senecionan-11,16-dione, 13,19-didehydro-12,18-dihydroxy- |
| riddeliin |
| riddeline |
| hsdb 7147 |
| ccris 4712 |
| riddeliine |
| 13,19-didehydro-12,18-dihydroxysenecionan-11,16-dione |
| riddelliine |
| (z)-ethylidene-hydroxy-(hydroxymethyl)-methylene-[?]dione |
| riddelline |
| 18-hydroxyseneciphylline |
| 23246-96-0 |
| 81yo8gx9j8 , |
| (1,6)dioxacyclododecino(2,3,4-gh)pyrrolizine-2,7-dione, 3-ethylidene-3,4,5,6,9,11,13,14,14a,14b-decahydro-6-hydroxy-6-(hydroxymethyl)-5-methylene-, (3z,6s,14ar,14br)- |
| unii-81yo8gx9j8 |
| CHEBI:63924 |
| (1,6)dioxacyclododecino(2,3,4-gh)pyrrolizine-2,7-dione, 3-ethylidene-3,4,5,6,9,11,13,14,14a,14b-decahydro-6-hydroxy-6-(hydroxymethyl)-5-methylene-, (6s-(3z,6r*,14as*,14bs*))- |
| (1,6)dioxacyclododecino(2,3,4-gh)pyrrolizine-2,7-dione, 3- ethylidene-3,4,5,6,9,11,13,14,14a,14b-decahydro-6-hydroxy-6- (hydroxymethyl)-5-methylene-, (3z,6s,14ar,14br)- |
| riddelline [hsdb] |
| [1,6]dioxacyclododecino[2,3,4-gh]pyrrolizine-2,7-dione, 3-ethylidene-3,4,5,6,9,11,13,14,14a,14b-decahydro-6-hydroxy-6-(hydroxymethyl)-5-methylene-, (3z,6s,14ar,14br)- |
| DTXSID4026006 |
| Q3935171 |
| (6s,9a1r,14ar,z)-3-ethylidene-6-hydroxy-6-(hydroxymethyl)-5-methylene-3,4,5,6,9,9a1,11,13,14,14a-decahydro-[1,6]dioxacyclododecino[2,3,4-gh]pyrrolizine-2,7-dione |
| SCHEMBL20771236 |
| HY-122099 |
| CS-0081774 |
| (1r,4z,7s,17r)-4-ethylidene-7-hydroxy-7-(hydroxymethyl)-6-methylidene-2,9-dioxa-14-azatricyclo[9.5.1.014,17]heptadec-11-ene-3,8-dione |
| AKOS040762283 |
| FS-6752 |
Riddelliine is a naturally occurring pyrrolizidine alkaloid that induces liver hemangiosarcomas in male and female F344 rats and male B6C3F(1) mice. It has been nominated to be classified as a reasonably anticipated human carcinogen by the US National Toxicology Program.
| Excerpt | Reference | Relevance |
|---|---|---|
| "Riddelliine residues have been found in meat, milk, and honey, and the plants may contaminate human food sources." | ( Toxicology and carcinogenesis studies of riddelliine (CAS No. 23246-96-0) in F344/N rats and B6C3F1 mice (gavage studies). , 2003) | 1.31 |
DNA adducts were formed in rats dosed with riddelliine, a tumorigenic pyrrolizidine alkaloid. A similar DNA adduct profile was detected in the livers of female F344 rats fed riddelline. The concentration-response curves of in vitro cytotoxicity of lasiocarpine and riddlliine defined in pooled human hepatocytes were translated to in vivo dose-response curve.
| Excerpt | Relevance | Reference |
|---|---|---|
| " We have evaluated the ability of RID to induce unscheduled DNA synthesis (UDS) in hepatocytes, S-phase synthesis (SPS) in hepatocytes, and micronuclei in bone marrow from animals dosed for 5 or 30 days in conjunction with prechronic toxicity testing conducted for the National Toxicology Program." | ( Evaluation of the potential of riddelliine to induce unscheduled DNA synthesis, S-phase synthesis, or micronuclei following in vivo treatment with multiple doses. Blazak, WF; Mirsalis, JC; Spalding, JW; Steinmetz, KL, 1993) | 0.57 |
| " A similar DNA adduct profile was detected in the livers of female F344 rats fed riddelliine, and a dose-response relationship was obtained for the level of the total (eight) DHR-derived DNA adducts and the level of the DHR-3'-dGMP adducts." | ( Metabolic activation of the tumorigenic pyrrolizidine alkaloid, riddelliine, leading to DNA adduct formation in vivo. Chan, PC; Chou, MW; Doerge, DR; Fu, PP; Yan, J; Yang, YC, 2001) | 0.78 |
| " Female rats and male and female mice were dosed for 2 years; due to high mortality, the study in male rats was terminated at week 72." | ( Toxicology and carcinogenesis studies of riddelliine (CAS No. 23246-96-0) in F344/N rats and B6C3F1 mice (gavage studies). , 2003) | 0.58 |
| " The dose groups were purposely designed to evaluate the dose-response relationship only in female rats and male mice." | ( Toxicity and carcinogenicity of riddelliine in rats and mice. Chan, PC; Haseman, JK; Nyska, A; Prejean, JD, 2003) | 0.6 |
| " Using LC-ESI/MS/MS analysis, we previously determined that four DNA adducts (DHP-dG-3, DHP-dG-4, DHP-dA-3, and DHP-dA-4) were formed in rats dosed with riddelliine, a tumorigenic pyrrolizidine alkaloid." | ( Full structure assignments of pyrrolizidine alkaloid DNA adducts and mechanism of tumor initiation. Cai, L; Fu, PP; Gamboa da Costa, G; Xia, Q; Yu, H; Zhao, Y, 2012) | 0.58 |
| " To develop a small animal model that may be used to compare the carcinogenic potential of the various DHPAs, male heterozygous p53 knockout mice were administered a short-term treatment of riddelliine 5, 15 or 45 mg kg(-1) bodyweight day(-1) by oral gavage for 14 days, or dosed a long-term treatment of riddelliine 1 mg kg(-1) bodyweight day(-1) in pelleted feed for 12 months." | ( Heterozygous p53 knockout mouse model for dehydropyrrolizidine alkaloid-induced carcinogenesis. Brown, AW; Colegate, SM; Hall, JO; Knoppel, EL; Panter, KE; Stegelmeier, BL, 2015) | 0.61 |
| " Concentration-response curves obtained from in vitro cytotoxicity assays in primary rat hepatocytes were converted to in vivo dose-response curves from which points of departure (PODs) were derived and that were compared to available literature data on in vivo liver toxicity." | ( Use of physiologically based kinetic modelling-facilitated reverse dosimetry to convert in vitro cytotoxicity data to predicted in vivo liver toxicity of lasiocarpine and riddelliine in rat. Chen, L; Louisse, J; Ning, J; Rietjens, IMCM; Wesseling, S, 2018) | 0.67 |
| " The concentration-response curves of in vitro cytotoxicity of lasiocarpine and riddelliine defined in pooled human hepatocytes were translated to in vivo dose-response curves by PBK models developed using kinetic data obtained from incubations with pooled tissue fractions from Chinese and Caucasian individuals, providing PBK models for the average Chinese and average Caucasian, respectively." | ( Use of an in vitro-in silico testing strategy to predict inter-species and inter-ethnic human differences in liver toxicity of the pyrrolizidine alkaloids lasiocarpine and riddelliine. Chen, L; Louisse, J; Ning, J; Rietjens, IMCM; Strikwold, M; Wesseling, S, 2019) | 0.93 |
| " The in vitro concentration-response curves obtained from primary rat hepatocytes were subsequently converted to in vivo dose-response curves from which points of departure (PoDs) were derived that were compared to available in vivo genotoxicity data." | ( Prediction of in vivo genotoxicity of lasiocarpine and riddelliine in rat liver using a combined in vitro-physiologically based kinetic modelling-facilitated reverse dosimetry approach. Chen, L; de Haan, L; Peijnenburg, A; Rietjens, IMCM, 2019) | 0.76 |
| Role | Description |
|---|---|
| genotoxin | A role played by a chemical compound to induce direct or indirect DNA damage. Such damage can potentially lead to the formation of a malignant tumour, but DNA damage does not lead inevitably to the creation of cancerous cells. |
| mutagen | An agent that increases the frequency of mutations above the normal background level, usually by interacting directly with DNA and causing it damage, including base substitution. |
| carcinogenic agent | A role played by a chemical compound which is known to induce a process of carcinogenesis by corrupting normal cellular pathways, leading to the acquistion of tumoral capabilities. |
| [role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res] | |
| Class | Description |
|---|---|
| pyrrolizine alkaloid | |
| organic heterotricyclic compound | An organic tricyclic compound in which at least one of the rings of the tricyclic skeleton contains one or more heteroatoms. |
| olefinic compound | Any organic molecular entity that contains at least one C=C bond. |
| macrodiolide | A macropolylide which contains two ester linkages in one macrocyclic ring. |
| [compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res] | |
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 0 (0.00) | 18.7374 |
| 1990's | 3 (6.82) | 18.2507 |
| 2000's | 24 (54.55) | 29.6817 |
| 2010's | 13 (29.55) | 24.3611 |
| 2020's | 4 (9.09) | 2.80 |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be strong demand-to-supply ratio for research on this compound.
| This Compound (35.02) All Compounds (24.57) |
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 0 (0.00%) | 5.53% |
| Reviews | 0 (0.00%) | 6.00% |
| Case Studies | 0 (0.00%) | 4.05% |
| Observational | 0 (0.00%) | 0.25% |
| Other | 45 (100.00%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||