Disease relevance of Senecifolinene

• The C-9 and C-7 monoesters and C-7, C-9 diesters of heliotridine with (S)-(+) and (R)-(-)-2-hydroxy-2-phenylbutyric acid were prepared, converted into their N-oxides, and compared with the corresponding C-9 monoesters of retronecine in the in vivo P388 lymphocytic leukemia screen [1].
• When jacobine was modified to form retronecine it no longer induced virus particles [2].

High impact information on Senecifolinene

• The two pyrrolizidine alkaloids that did not elicit DNA repair were retronecine which lacks a necic acid component and ligularinine which lacks the unsaturated double bond at the 1,2-position of the pyrrolizidine ring [3].
• These alkaloids, except retronecine, showed a positive response in the test with hamster hepatocytes, but in the test with mouse hepatocytes clivorine in addition to retronecine was also negative [3].
• The toxicokinetics of riddelliine and two metabolites, the N-oxide and retronecine, were determined in serum following an oral gavage dose in male and female rats and mice using a validated liquid chromatography-electrospray mass spectrometric method [4].
• The formation of the pyrrolic alcohol glutathione (GSH) conjugates of two different types of pyrrolizidine alkaloids (PAs), i.e. clivorine (an otonecine-type PA) and retrorsine (a retronecine-type PA), was investigated with rat microsomes in the presence of GSH [5].
• Since VL was suspected to be derived from pyrrolizidine alkaloids (PAs) acquired as an adult, tests for feeding response to and oral administration of four PAs (a 4:1 mixture of intermedine/lycopsamine, heliotrine, monocrotaline, and retronecine) were conducted [6].

Chemical compound and disease context of Senecifolinene

• The isobutyryl monoester of retronecine was also able to induce virus particle production, but the isobutyryl monoester pyrrole was unexpectedly inactive as an inducer [2].

Biological context of Senecifolinene

• Enzymic hydrolysis of retronecine di-isovalerate occurred primarily at the allylic 9-ester group [7].
• Pupae contain ca. 45% of the labeled retronecine originally ingested, metabolized, and stored by larvae; ca. 12% of larval radioactivity could be recovered from the defensive secretions of adults sampled successively over two and a half months [8].
• Esterification at C-9 v. C-7 can be distinguished for non-cyclic esters of retronecine in the positive ion spectra [9].

Anatomical context of Senecifolinene

• A long-term feeding experiment lasting for almost four months revealed that retronecine esters synthesized from [14C]retronecine in the larvae are transferred from larvae via pupae into the exocrine glands of adult beetles [8].

Associations of Senecifolinene with other chemical compounds

• Lactating rats dosed with these differently labelled pyrrolizidine alkaloids (PAs) excreted within 3 h approx. 0.08% of the applied radioactivity in the milk mainly as yet not identified water-soluble retronecine-derived metabolites and with approx. 0.02% as unchanged PAs [10].

Gene context of Senecifolinene

• In contrast, a smaller amount of danaidone (5.7 to 7.0 microg/ male) was formed when males ingested retronecine or heliotrine, and those fed with an HCI salt of monocrotaline or retrorsine produced only traces of danaidone (<0.5 microg/male) [11].
• Results from this study indicate that (i) DHP is a common reactive metabolite for retronecine-type of pyrrolizidine alkaloids, (ii) the formation of DHP-derived DNA adducts in the liver DNA of rats treated with monocrotaline suggests that monocrotaline-induced tumorigenicity is through a genotoxic mechanism [12].

Analytical, diagnostic and therapeutic context of Senecifolinene

• A third retronecine-based ELISA detects 3 with an I50 of 3000 +/- 600 ppb (3 +/- 0.6 ppm) and detection limits of 600-10,000 ppb [13].
• The simple necine base retronecine was not present at detectable levels in the perfusion medium [14].

References