luotonin A: structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]
| ID Source | ID |
|---|---|
| PubMed CID | 10334120 |
| CHEMBL ID | 19163 |
| CHEBI ID | 172341 |
| MeSH ID | M0459550 |
| Synonym |
|---|
| luotonin a |
| 3,11,21-triazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,13,15,17,19-nonaen-10-one |
| CHEBI:172341 |
| CHEMBL19163 |
| bdbm50223906 |
| 205989-12-4 |
| 3,11,21-triazapentacyclo[11.8.0.02,11.0,.01,2]henicosa-1(21),2,4,6,8,13,15,17,19-nonaen-10-one |
| luotonine a |
| 3,11,21-triazapentacyclo[11.8.0.0?,??.0?,?.0??,??]henicosa-1(21),2,4,6,8,13,15,17,19-nonaen-10-one |
| DTXSID501347723 |
| HY-119458 |
| CS-0068434 |
Luotonin A is a pyrroloquinazolinoquinoline alkaloid isolated from the Chinese herbal medicinal plant Peganum nigellastrum. It has been shown to stabilize the human topoisomerase I-DNA covalent binary complex in the same fashion as camptothecin. Lu serotonin A was found to be a potent CYP1A inhibitor that might cause drug-drug interactions when co-administrated with CYP 1A substrates.
| Excerpt | Reference | Relevance |
|---|---|---|
| "Luotonin A is a cytotoxic pyrroloquinazolinoquinoline alkaloid that has been shown to stabilize the human topoisomerase I-DNA covalent binary complex in the same fashion as the antitumor alkaloid camptothecin. " | ( Synthesis and biochemical properties of E-ring modified luotonin A derivatives. Cagir, A; Eisenhauer, BM; Gao, R; Hecht, SM; Jones, SH, 2004) | 2.01 |
| "Luotonin A is a cytotoxic alkaloid that has been shown to inhibit topoisomerase I via stabilization of the binary complex topoisomerase-DNA in the same fashion as camptothecin. " | ( Synthesis and cytotoxic activity of substituted luotonin A derivatives. Beretta, GL; Dallavalle, S; Merlini, L; Tinelli, S; Zunino, F, 2004) | 2.02 |
| "Luotonin A is a natural camptothecin analogue that lacks this functional group and therefore shows a much-improved stability, but at the cost of a lower activity." | ( B-ring-aryl substituted luotonin A analogues with a new binding mode to the topoisomerase 1-DNA complex show enhanced cytotoxic activity. Bianchini, G; Fernández-Marcelo, T; González-Ruiz, V; Iniesta, P; Martín, MA; Menéndez, JC; Olives, AI; Pascua, I; Ramos, MT; Ribelles, P; Sridharan, V, 2014) | 1.43 |
| "Luotonin A was found to be a potent CYP1A inhibitor that might cause drug-drug interactions when co-administrated with CYP1A substrates." | ( In vitro inhibitory effect of luotonin A on human CYP1A. Jahng, Y; Kwon, OK; Lee, S, 2012) | 1.39 |
| "Luotonin A is a pyrroloquinazolinoquinoline alkaloid isolated from the Chinese herbal medicinal plant Peganum nigellastrum. " | ( Luotonin A. A naturally occurring human DNA topoisomerase I poison. Cagir, A; Eisenhauer, BM; Gao, R; Hecht, SM; Jones, SH, 2003) | 3.2 |
| Class | Description |
|---|---|
| quinazolines | Any organic heterobicyclic compound based on a quinazoline skeleton and its substituted derivatives. |
| [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] | |
| Protein | Taxonomy | Measurement | Average | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| DNA topoisomerase 2-alpha | Homo sapiens (human) | IC50 (µMol) | 28.5000 | 0.4800 | 4.3564 | 9.9400 | AID57196 |
| DNA topoisomerase 2-beta | Homo sapiens (human) | IC50 (µMol) | 28.5000 | 0.0300 | 2.7716 | 7.8000 | AID57196 |
| Histone deacetylase 1 | Homo sapiens (human) | IC50 (µMol) | 6.4000 | 0.0001 | 0.5543 | 9.9000 | AID1201146 |
| Histone deacetylase 2 | Homo sapiens (human) | IC50 (µMol) | 6.4000 | 0.0001 | 0.7221 | 9.9700 | AID1201146 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
| Assay ID | Title | Year | Journal | Article |
|---|---|---|---|---|
| AID1201133 | Cell cycle arrest in human HeLa cells assessed as accumulation at G0 phase at 8 uM after 48 hrs by propidium iodide staining-based flow cytometric analysis (Rvb = 3%) | 2015 | European journal of medicinal chemistry, Apr-13, Volume: 94 | Luotonin-A based quinazolinones cause apoptosis and senescence via HDAC inhibition and activation of tumor suppressor proteins in HeLa cells. |
| AID1201130 | Cell cycle arrest in human HeLa cells assessed as accumulation at G0/G1 phase at 4 uM after 48 hrs by propidium iodide staining-based flow cytometric analysis (Rvb = 62%) | 2015 | European journal of medicinal chemistry, Apr-13, Volume: 94 | Luotonin-A based quinazolinones cause apoptosis and senescence via HDAC inhibition and activation of tumor suppressor proteins in HeLa cells. |
| AID1201132 | Cell cycle arrest in human HeLa cells assessed as accumulation at G2/M phase at 4 uM after 48 hrs by propidium iodide staining-based flow cytometric analysis (Rvb = 31%) | 2015 | European journal of medicinal chemistry, Apr-13, Volume: 94 | Luotonin-A based quinazolinones cause apoptosis and senescence via HDAC inhibition and activation of tumor suppressor proteins in HeLa cells. |
| AID202707 | Percent inhibitory activity of 10 uM of compound against growth of Saccharomyces cerevisiae transfected with human topoisomerase-1 in medium containing galactose | 2004 | Bioorganic & medicinal chemistry letters, May-03, Volume: 14, Issue:9 | Synthesis and biochemical properties of E-ring modified luotonin A derivatives. |
| AID1201124 | Cytotoxicity against human HeLa cells after 72 hrs by MTT assay | 2015 | European journal of medicinal chemistry, Apr-13, Volume: 94 | Luotonin-A based quinazolinones cause apoptosis and senescence via HDAC inhibition and activation of tumor suppressor proteins in HeLa cells. |
| AID1201134 | Cell cycle arrest in human HeLa cells assessed as accumulation at G1 phase at 8 uM after 48 hrs by propidium iodide staining-based flow cytometric analysis (Rvb = 68%) | 2015 | European journal of medicinal chemistry, Apr-13, Volume: 94 | Luotonin-A based quinazolinones cause apoptosis and senescence via HDAC inhibition and activation of tumor suppressor proteins in HeLa cells. |
| AID1659503 | Inhibition of human TOP1 assessed as decrease in relaxation of supercoiled DNA using supercoiled plasmid DNA pGEM1 as substrate at 1 uM preincubated for 30 mins by SDS gel electrophoresis method (Rvb = 1%) | 2020 | Bioorganic & medicinal chemistry, 05-01, Volume: 28, Issue:9 | A-ring and E-ring modifications of the cytotoxic alkaloid Luotonin A: Synthesis, computational and biological studies. |
| AID1201135 | Cell cycle arrest in human HeLa cells assessed as accumulation at S phase at 8 uM after 48 hrs by propidium iodide staining-based flow cytometric analysis (Rvb = 10%) | 2015 | European journal of medicinal chemistry, Apr-13, Volume: 94 | Luotonin-A based quinazolinones cause apoptosis and senescence via HDAC inhibition and activation of tumor suppressor proteins in HeLa cells. |
| AID1378656 | Cytotoxicity against human KB cells assessed as reduction in cell viability at 12.5 uM after 72 hrs by MTT assay | 2017 | European journal of medicinal chemistry, Sep-29, Volume: 138 | Design, synthesis and antiproliferative activity of decarbonyl luotonin analogues. |
| AID1201143 | Downregulation of HDAC-5 mRNA expression in human HeLa cells at 4 uM after 48 hrs by RT-PCR analysis | 2015 | European journal of medicinal chemistry, Apr-13, Volume: 94 | Luotonin-A based quinazolinones cause apoptosis and senescence via HDAC inhibition and activation of tumor suppressor proteins in HeLa cells. |
| AID1201123 | Cytotoxicity against human MCF7 cells after 72 hrs by MTT assay | 2015 | European journal of medicinal chemistry, Apr-13, Volume: 94 | Luotonin-A based quinazolinones cause apoptosis and senescence via HDAC inhibition and activation of tumor suppressor proteins in HeLa cells. |
| AID1659510 | Antiproliferative activity against human SW480 cells assessed as reduction in cell viability at 20 uM measured after 72 hours by MTT assay relative to control | 2020 | Bioorganic & medicinal chemistry, 05-01, Volume: 28, Issue:9 | A-ring and E-ring modifications of the cytotoxic alkaloid Luotonin A: Synthesis, computational and biological studies. |
| AID202699 | Percent inhibitory activity of 0.5 uM of compound against growth of Saccharomyces cerevisiae transfected with human topoisomerase-1 in medium containing galactose | 2004 | Bioorganic & medicinal chemistry letters, May-03, Volume: 14, Issue:9 | Synthesis and biochemical properties of E-ring modified luotonin A derivatives. |
| AID1201127 | Selectivity index, ratio of IC50 for HEK cells to IC50 for human MCF7 cells | 2015 | European journal of medicinal chemistry, Apr-13, Volume: 94 | Luotonin-A based quinazolinones cause apoptosis and senescence via HDAC inhibition and activation of tumor suppressor proteins in HeLa cells. |
| AID152265 | Cytotoxic activity against mouse leukemia P-388 cells | 2004 | Bioorganic & medicinal chemistry letters, Mar-08, Volume: 14, Issue:5 | Novel quinazoline-quinoline alkaloids with cytotoxic and DNA topoisomerase II inhibitory activities. |
| AID248760 | In vitro inhibitory concentration against human lung large cell carcinoma cell line, H460 (after 1 hour exposure) | 2004 | Bioorganic & medicinal chemistry letters, Dec-06, Volume: 14, Issue:23 | Synthesis and cytotoxic activity of substituted luotonin A derivatives. |
| AID1201141 | Downregulation of HDAC-1 mRNA expression in human HeLa cells at 4 uM after 48 hrs by RT-PCR analysis | 2015 | European journal of medicinal chemistry, Apr-13, Volume: 94 | Luotonin-A based quinazolinones cause apoptosis and senescence via HDAC inhibition and activation of tumor suppressor proteins in HeLa cells. |
| AID1201147 | Induction of human p16 promoter activity transfected in human HeLa cells at 4 uM after 48 hrs by luciferase-based luminescence assay | 2015 | European journal of medicinal chemistry, Apr-13, Volume: 94 | Luotonin-A based quinazolinones cause apoptosis and senescence via HDAC inhibition and activation of tumor suppressor proteins in HeLa cells. |
| AID1201142 | Downregulation of HDAC-2 mRNA expression in human HeLa cells at 4 uM after 48 hrs by RT-PCR analysis | 2015 | European journal of medicinal chemistry, Apr-13, Volume: 94 | Luotonin-A based quinazolinones cause apoptosis and senescence via HDAC inhibition and activation of tumor suppressor proteins in HeLa cells. |
| AID1201125 | Cytotoxicity against human K562 cells after 72 hrs by MTT assay | 2015 | European journal of medicinal chemistry, Apr-13, Volume: 94 | Luotonin-A based quinazolinones cause apoptosis and senescence via HDAC inhibition and activation of tumor suppressor proteins in HeLa cells. |
| AID202703 | Percent inhibitory activity of 1 uM of compound against growth of Saccharomyces cerevisiae transfected with human topoisomerase-1 in medium containing galactose | 2004 | Bioorganic & medicinal chemistry letters, May-03, Volume: 14, Issue:9 | Synthesis and biochemical properties of E-ring modified luotonin A derivatives. |
| AID202700 | Percent inhibitory activity of 0.5 uM of compound against growth of Saccharomyces cerevisiae transfected with human topoisomerase-1 in medium containing raffinose | 2004 | Bioorganic & medicinal chemistry letters, May-03, Volume: 14, Issue:9 | Synthesis and biochemical properties of E-ring modified luotonin A derivatives. |
| AID1201144 | Change in HDAC-6 mRNA expression in human HeLa cells at 4 uM after 48 hrs by RT-PCR analysis | 2015 | European journal of medicinal chemistry, Apr-13, Volume: 94 | Luotonin-A based quinazolinones cause apoptosis and senescence via HDAC inhibition and activation of tumor suppressor proteins in HeLa cells. |
| AID307323 | Growth inhibition of human CEM cells by Alamar blue assay | 2007 | Bioorganic & medicinal chemistry, Jun-15, Volume: 15, Issue:12 | Synthesis and topoisomerase poisoning activity of A-ring and E-ring substituted luotonin A derivatives. |
| AID1201126 | Cytotoxicity against HEK cells after 72 hrs by MTT assay | 2015 | European journal of medicinal chemistry, Apr-13, Volume: 94 | Luotonin-A based quinazolinones cause apoptosis and senescence via HDAC inhibition and activation of tumor suppressor proteins in HeLa cells. |
| AID1201131 | Cell cycle arrest in human HeLa cells assessed as accumulation at S phase at 4 uM after 48 hrs by propidium iodide staining-based flow cytometric analysis (Rvb = 7%) | 2015 | European journal of medicinal chemistry, Apr-13, Volume: 94 | Luotonin-A based quinazolinones cause apoptosis and senescence via HDAC inhibition and activation of tumor suppressor proteins in HeLa cells. |
| AID1201138 | Upregulation of p53 mRNA expression in human HeLa cells at 4 uM after 48 hrs by RT-PCR analysis | 2015 | European journal of medicinal chemistry, Apr-13, Volume: 94 | Luotonin-A based quinazolinones cause apoptosis and senescence via HDAC inhibition and activation of tumor suppressor proteins in HeLa cells. |
| AID307321 | Growth inhibition of HeLa cells after 4 days | 2007 | Bioorganic & medicinal chemistry, Jun-15, Volume: 15, Issue:12 | Synthesis and topoisomerase poisoning activity of A-ring and E-ring substituted luotonin A derivatives. |
| AID1587305 | Cytotoxicity against mouse P388 cells assessed as reduction in cell growth | 2019 | European journal of medicinal chemistry, Jun-01, Volume: 171 | A comprehensive review of topoisomerase inhibitors as anticancer agents in the past decade. |
| AID1859463 | Antiproliferative activity gainst mouse P388 cells assessed as cell growth inhibition | 2022 | European journal of medicinal chemistry, Jun-05, Volume: 236 | Topoisomerase I inhibitors: Challenges, progress and the road ahead. |
| AID202704 | Percent inhibitory activity of 1 uM of compound against growth of Saccharomyces cerevisiae transfected with human topoisomerase-1 in medium containing raffinose | 2004 | Bioorganic & medicinal chemistry letters, May-03, Volume: 14, Issue:9 | Synthesis and biochemical properties of E-ring modified luotonin A derivatives. |
| AID1659511 | Antiproliferative activity against human HL60 cells assessed as reduction in cell viability at 20 uM measured after 72 hrs by MTT assay relative to control | 2020 | Bioorganic & medicinal chemistry, 05-01, Volume: 28, Issue:9 | A-ring and E-ring modifications of the cytotoxic alkaloid Luotonin A: Synthesis, computational and biological studies. |
| AID307320 | Growth inhibition of adriamycin-resistant MCF7 cells after 4 days | 2007 | Bioorganic & medicinal chemistry, Jun-15, Volume: 15, Issue:12 | Synthesis and topoisomerase poisoning activity of A-ring and E-ring substituted luotonin A derivatives. |
| AID1201139 | Upregulation of p21 mRNA expression in human HeLa cells at 4 uM after 48 hrs by RT-PCR analysis | 2015 | European journal of medicinal chemistry, Apr-13, Volume: 94 | Luotonin-A based quinazolinones cause apoptosis and senescence via HDAC inhibition and activation of tumor suppressor proteins in HeLa cells. |
| AID1201145 | Change in HDAC-7 mRNA expression in human HeLa cells at 4 uM after 48 hrs by RT-PCR analysis | 2015 | European journal of medicinal chemistry, Apr-13, Volume: 94 | Luotonin-A based quinazolinones cause apoptosis and senescence via HDAC inhibition and activation of tumor suppressor proteins in HeLa cells. |
| AID1659502 | Inhibition of human TOP1 assessed as decrease in relaxation of supercoiled DNA using supercoiled plasmid DNA pGEM1 as substrate at 10 uM preincubated for 30 mins by SDS gel electrophoresis method (Rvb = 1%) | 2020 | Bioorganic & medicinal chemistry, 05-01, Volume: 28, Issue:9 | A-ring and E-ring modifications of the cytotoxic alkaloid Luotonin A: Synthesis, computational and biological studies. |
| AID1659501 | Inhibition of human TOP1 assessed as decrease in relaxation of supercoiled DNA using supercoiled plasmid DNA pGEM1 as substrate at 100 uM preincubated for 30 mins by SDS gel electrophoresis method (Rvb = 1%) | 2020 | Bioorganic & medicinal chemistry, 05-01, Volume: 28, Issue:9 | A-ring and E-ring modifications of the cytotoxic alkaloid Luotonin A: Synthesis, computational and biological studies. |
| AID248784 | In vitro inhibitory concentration against human lung large cell carcinoma cell line, H460 (after 72 hours exposure) | 2004 | Bioorganic & medicinal chemistry letters, Dec-06, Volume: 14, Issue:23 | Synthesis and cytotoxic activity of substituted luotonin A derivatives. |
| AID202708 | Percent inhibitory activity of 10 uM of compound against growth of Saccharomyces cerevisiae transfected with human topoisomerase-1 in medium containing raffinose | 2004 | Bioorganic & medicinal chemistry letters, May-03, Volume: 14, Issue:9 | Synthesis and biochemical properties of E-ring modified luotonin A derivatives. |
| AID57196 | Inhibitory activity against human DNA topoisomerase II | 2004 | Bioorganic & medicinal chemistry letters, Mar-08, Volume: 14, Issue:5 | Novel quinazoline-quinoline alkaloids with cytotoxic and DNA topoisomerase II inhibitory activities. |
| AID1201129 | Selectivity index, ratio of IC50 for HEK cells to IC50 for human K562 cells | 2015 | European journal of medicinal chemistry, Apr-13, Volume: 94 | Luotonin-A based quinazolinones cause apoptosis and senescence via HDAC inhibition and activation of tumor suppressor proteins in HeLa cells. |
| AID1201146 | Inhibition of HDAC1/2 in human HeLa cells using color de lys as substrate after 30 mins by colorimetric analysis | 2015 | European journal of medicinal chemistry, Apr-13, Volume: 94 | Luotonin-A based quinazolinones cause apoptosis and senescence via HDAC inhibition and activation of tumor suppressor proteins in HeLa cells. |
| AID1201140 | Downregulation of EZH2 mRNA expression in human HeLa cells at 4 uM after 48 hrs by RT-PCR analysis | 2015 | European journal of medicinal chemistry, Apr-13, Volume: 94 | Luotonin-A based quinazolinones cause apoptosis and senescence via HDAC inhibition and activation of tumor suppressor proteins in HeLa cells. |
| AID1201136 | Cell cycle arrest in human HeLa cells assessed as accumulation at G2/M phase at 8 uM after 48 hrs by propidium iodide staining-based flow cytometric analysis (Rvb = 19%) | 2015 | European journal of medicinal chemistry, Apr-13, Volume: 94 | Luotonin-A based quinazolinones cause apoptosis and senescence via HDAC inhibition and activation of tumor suppressor proteins in HeLa cells. |
| AID307324 | Growth inhibition of topoisomerase 1 mutated CEM/C2 cells by Alamar blue assay | 2007 | Bioorganic & medicinal chemistry, Jun-15, Volume: 15, Issue:12 | Synthesis and topoisomerase poisoning activity of A-ring and E-ring substituted luotonin A derivatives. |
| AID1859464 | Inhibition of full-length recombinant human Top1 expressed in baculovirus infected Sf9 insect cells at 5 uM incubated for 30 mins relative to control | 2022 | European journal of medicinal chemistry, Jun-05, Volume: 236 | Topoisomerase I inhibitors: Challenges, progress and the road ahead. |
| AID307322 | Growth inhibition of MCF7 cells after 4 days | 2007 | Bioorganic & medicinal chemistry, Jun-15, Volume: 15, Issue:12 | Synthesis and topoisomerase poisoning activity of A-ring and E-ring substituted luotonin A derivatives. |
| AID1201137 | Induction of senescence in human HeLa cells at 4 uM after 72 hrs by X-gal staining-based beta-galactosidase assay | 2015 | European journal of medicinal chemistry, Apr-13, Volume: 94 | Luotonin-A based quinazolinones cause apoptosis and senescence via HDAC inhibition and activation of tumor suppressor proteins in HeLa cells. |
| AID1201128 | Selectivity index, ratio of IC50 for HEK cells to IC50 for human HeLa cells | 2015 | European journal of medicinal chemistry, Apr-13, Volume: 94 | Luotonin-A based quinazolinones cause apoptosis and senescence via HDAC inhibition and activation of tumor suppressor proteins in HeLa cells. |
| [information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||||
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 0 (0.00) | 18.7374 |
| 1990's | 0 (0.00) | 18.2507 |
| 2000's | 16 (41.03) | 29.6817 |
| 2010's | 18 (46.15) | 24.3611 |
| 2020's | 5 (12.82) | 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 moderate demand-to-supply ratio for research on this compound.
| This Compound (20.20) All Compounds (24.57) |
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 0 (0.00%) | 5.53% |
| Reviews | 3 (7.69%) | 6.00% |
| Case Studies | 0 (0.00%) | 4.05% |
| Observational | 0 (0.00%) | 0.25% |
| Other | 36 (92.31%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||