Luotonine A

Description

Luotonin A is an alkaloid originally isolated from a plant used in traditional Chinese medicine. It inhibits the growth of mouse leukemia P388 cells (IC₅₀ = 1.8 μg/ml). Luotonin A is structurally similar to the alkaloid camptothecin and, like camptothecin, it binds to and stabilizes the topoisomerase I-DNA binary complex, leading to DNA breakage and cell death (IC₅₀ = 5.07-12.6 μM). Also like camptothecin, luotonin A forms non-covalent complexes with double-stranded DNA in the minor groove and this association can be followed by native fluorescence associated with the aromatic and heterocyclic ring structure. Luotonin A also selectively inhibits the cytochrome P450 (CYP) isoforms CYP1A1 and CYP1A2 (IC₅₀ = ~6 μM for each) in human liver microsomes.

The Uses of Luotonine A

Luotonine A is a pyrroloquinoline alkaloid, a topoisomerase I inhibitor and a potent CYP1A inhibitor.

Definition

ChEBI: Luotonin A is a member of quinazolines.

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].

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).