205989-12-4

Usage

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

• 82745-72-0 2-(((4-methylphenyl)sulfonyl)oxy)benzoic acid 
• 872998-61-3 2,4-dibromoquinazoline 
• 28144-70-9 anthranilic acid amide 
• 807354-69-4 3-[2-(2-bromoindol-3-yl)ethyl]-4(3H)-quinazolinone 
• 853029-99-9 3-[(Z)-2-iodo-3-phenylprop-2-enyl]-4-oxo-3,4-dihydroquinazoline-2-carbonitrile 

Downstream Products

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

Relevant academic research and scientific papers

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.

Concise synthesis of quinazoline alkaloids, luotonins A and B, and rutaecarpine

The total synthesis of luotonin A was achieved in excellent yield by using a Pd-assisted biaryl coupling reaction of N-(bromoquinolinyl)methylquinazolinone with Cy3P and KOAc. The successive treatment of luotonin A with NBS and aq. AgNO3 gave luotonin B in good yield. Although the Pd-assisted coupling reaction of N-(2-bromoindolyl)ethylquinazolinone with Cy3P and KOAc yielded rutaecarpine in poor yield, N-acetate under the same reaction conditions yielded the desired rutaecarpine directly in excellent yield. Graphical Abstract.

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.

Luotonin A and Its Derivatives as Novel Antiviral and Antiphytopathogenic Fungus Agents

Plant diseases caused by viruses and fungi have posed a serious threat to global agricultural production. The discovery of new leads based on natural products is an important way to innovate pesticides. In this work, natural product luotonin A was found to have good antiviral activity against tobacco mosaic virus (TMV) for the first time. A series of luotonin A derivatives were designed, synthesized, and evaluated for their antiviral activities and fungicidal activities systematically. Most compounds displayed better antiviral activities against TMV than commercial ribavirin. Compounds 9k, 12b, and 12d displayed about similar inhibitory effects as ningnanmycin (inhibitory rates of 55, 57, and 59% at 500 μg/mL for inactivation, curative, and protection activities in vivo, respectively), the best antiviral agent at present, and emerged as novel antiviral leads for further research. We selected 9k for further antiviral mechanism research via transmission electron microscopy and molecular docking, which revealed that compound 9k can interact with TMV coat protein through the hydrogen bond, leading to its polymerization, thus preventing virus assembly. Further fungicidal activity tests showed that these compounds also showed broad-spectrum fungicidal activities against 14 kinds of phytopathogenic fungi. Especially, compound 14 with a 100% antifungal effect against Botrytis cinereal emerged as a lead for further research. This work provides a reference for the development of agricultural active ingredients based on Chinese medicine plants.

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 derivatives in preparation of drugs for preventing or resisting plant diseases

The invention relates to natural pharmaceutical chemistry field and technical field of biopesticides and discloses application of any compound of luotonin A derivatives (Ia)-(Ii) in the preparation ofdrugs for preventing or resisting grape gray mold rot and rice blast. The compounds provided by the invention are derived from natural structure derivatives of a Chinese herbal medicine, namely peganum nigellastrum, have the characteristics of no pollution, safety and high efficiency, have the advantages of natural source pesticides, can be developed into plant source pesticides for producing environment-friendly and pollution-free agricultural products and belong to novel biopesticides.

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.

Total synthesis of luotonin A and 14-substituted analogues

A new and concise synthesis of luotonin A was achieved from the previously described compounds ethyl 4-oxo-3,4-dihydroquinazoline-2-carboxylate and 1-(2-nitrophenyl)prop-2-en-1-one. New 14-substituted luotonin A analogues were prepared using 14-chloroluotonin A as the key intermediate. This journal is The Royal Society of Chemistry.

Short and efficient total synthesis of luotonin A and 22-hydroxyacuminatine using a common cascade strategy

(Chemical Equation Presented) Total syntheses of 22-hydroxyacuminatine and luotonin A were achieved in direct fashion and high overall yields (16% in eight steps and 47% in five steps, respectively). A mild cascade methodology was successfully applied in both syntheses as a common strategy. The new approach presents the advantages of short routes, high overall yields, use of stable intermediates, and ease of operations.

Total synthesis of luotonin and a small library of AB-ring substituted analogues by cascade radical annulation of isonitriles

A four-step total synthesis of luotonin is deployed to make a small library of AB-ring substituted analogues. These analogues show weak activity in a standard topoisomerase I mediated DNA cleavage assay. Georg Thieme Verlag Stuttgart.