205989-12-4

Basic information

• Product Name: Luotonine A
• Synonyms: Luotonine A;LUMDXNLBIYLTER-UHFFFAOYSA-N
• CAS NO: 205989-12-4
• Molecular Formula: C₁₈H₁₁N₃O
• Molecular Weight: 285.29944
• Mol File: 205989-12-4.mol
• Article Data: 12

Chemical Properties

• Melting Point: 283-285 °C
• Boiling Point: 530.9±60.0 °C(Predicted)
• Appearance: /
• Density: 1.44±0.1 g/cm3(Predicted)
• Solubility: ≤3mg/ml in DMSO;3mg/ml in dimethyl formamide
• PKA: 1.61±0.20(Predicted)
• CAS DataBase Reference: Luotonine A(CAS DataBase Reference)
• NIST Chemistry Reference: Luotonine A(205989-12-4)
• EPA Substance Registry System: Luotonine A(205989-12-4)

Safety Data

• Hazardous Substances Data: 205989-12-4(Hazardous Substances Data)

Usage

Description

Luotonin A is an alkaloid originally isolated from a plant used in traditional Chinese medicine. It is structurally similar to the alkaloid camptothecin and possesses the ability to inhibit the growth of mouse leukemia P388 cells. Luotonin A binds to and stabilizes the topoisomerase I-DNA binary complex, leading to DNA breakage and cell death. Additionally, it forms non-covalent complexes with double-stranded DNA in the minor groove and selectively inhibits the cytochrome P450 (CYP) isoforms CYP1A1 and CYP1A2 in human liver microsomes.

Uses

Used in Anticancer Applications:
Luotonin A is used as an anticancer agent for its ability to inhibit the growth of mouse leukemia P388 cells and stabilize the topoisomerase I-DNA binary complex, leading to DNA breakage and cell death.
Used in Drug Development:
Luotonin A is used as a potential drug candidate for its structural similarity to camptothecin and its ability to selectively inhibit cytochrome P450 (CYP) isoforms CYP1A1 and CYP1A2 in human liver microsomes.
Used in DNA Interaction Studies:
Luotonin A is used as a research tool for studying its non-covalent complexes with double-stranded DNA in the minor groove and the associated native fluorescence, which can provide insights into DNA-drug interactions and potential therapeutic applications.

in vitro

luotonin a was isolated as a pyrroloquinazolinoquinoline alkaloid from the chinese medicinal plant peganum nigellastrum. luotonin a could stabilize the human dna topoisomerase i-dna covalent binary complex and mediate topoisomerase i-dependent cytotoxicity in intact cells. similar to camptothecin, luotonin a was able to effect concentration-dependent stabilization of the enzyme-dna binary complex. however, neither camptothecin nor luotonin a had any measurable effect on dna in the absence of topoisomerase i. in addition, luotonin a was evaluated in a strain of saccharomyces cerevisiae lacking yeast topoisomerase i, but having a plasmid having the human topoisomerase i gene under the control of a galactose promoter. results showed that luotonin a at 1 μm concentration could produce 36% inhibition of growth in the presence of galactose. moreover, in replicate experiments, lutonin a exhibited ic50 values from 5.7 to 12.6 μm in the presence of galactose, while the comparable values for camptothecin were from 0.74 to 0.86 μm [1].

IC 50

1.8 μg/ml for p-388 cell line

references

[1] cagir, a. ,jones, s.h.,gao, r., et al. luotonin a. a naturally occurring human dna topoisomerase i poison. journal of the american chemical society 125(45), 13628-13629 (2003).

Upstream product

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Downstream Products

• 205989-13-5 quino[2',3':3,4]pyrrolo[2,1-b]quinazolin-13-hydroxy-11-one 

Relevant articles and documents

Regioselective quinazolinone-directed ortho lithiation of quinazolinoylquinoline: Practical synthesis of naturally occurring human DNA topoisomerase I poison luotonin A and luotonins B and E

A regioselective quinazolinone-directed ortho lithiation on an adjacent quinoline moiety has been used as a key step for a short, efficient, and practical synthesis of the human DNA topoisomerase I poison luotonin A and luotonins B and E. The quinazolinoylquinoline 5 on treatment with in situ-generated nonnucleophilic mesityllithium furnished the desired dilithiated intermediate 6, which on treatment with formaldehyde followed by Mitsunobu ring closure reaction gave luotonin A (1a) in very good yield. The reaction of dilithiated intermediate 6 with DMF directly furnished luotonin B (1b) in 81% yield. Luotonin B (1b) on methylation with p-TSA/methanol gave luotonin E (1c) in 82% yield.

Discovery of luotonin A analogues as potent fungicides and insecticides: Design, synthesis and biological evaluation inspired by natural alkaloid

The prevention and control of plant diseases and insect pests is the most crucial issue facing crop protection. To discover novel pesticide candidates with diverse chemical structures from natural products, a series of luotonin A analogues were designed, synthesized and evaluated for their antifungal and insecticidal activities. Most of these compounds exhibited potent activity against Botrytis cinerea, Magnaporthe oryzae and Aphis craccivora. Among them, the antifungal activity of compound 10s against B. cinerea was comparable to azoxystrobin (EC50 = 0.09 mM) and against M. oryzae (EC50 = 0.19 mM) was slightly weaker than that of azoxystrobin (EC50 = 0.17 mM). Compounds 10k and 10o are the most active compounds against A. craccivora having identical mortality value of 42.05% at 50 μg/mL, respectively, which were slightly lower than pymetrozine (51.14%) at the same concentration. Revealed morphological changes of the fungal cell surface by scanning electron microscopy indicated that luotonin A analogues might exert their antifungal activity by destroying fungal cell membrane and cell wall. Furthermore, the results of the in vivo protective and curative activities of the compound 10s against S. sclerotiorum and B. cinerea showed that the curative effect was stronger than its protective effect and the curative effects reached 67.17% and 73.82% at 80 μg/mL respectively. The above results further demonstrated the potential of luotonin A analogues as novel fungicides and insecticides.

Concise approach to mono- And disubstituted luotonin A analogs and their cytotoxicity test

A concise approach for the preparation of luotonin A analogs has been developed. The new synthetic route contains an anion-assisted intramolecular double hetero Diels Alder reaction and a direct oxidative cross coupling reaction. Some synthetic luotonin A analogs show cytotoxic activities against Daudi and Jurkat human cancer cells as potent as camptothecin.

Application of Luotonin A to prevention and treatment of aphid

The invention discloses application of a Luotonin A compound to prevention and treatment of green peach aphid, Chinese scholar tree aphid, hickory nut aphid and alfalfa aphid. The compound is high in aphid killing activity, can prevent and treat aphid harms and can serve as a new aphid-killing forerunner to be developed. Due to the fact that the compound is from a natural product of Chinese herbal medicine peganum nigellastrum bunge, the compound has the advantages of being free of pollution, safe and efficient, has the advantages of natural source pesticide and can serve as new potential forerunner molecules of plant source pesticide for producing green and pollution-free agricultural products.