Cryptolepine

Whereas j3-carboline derivatives abound in nature, other carbolines are virtually unknown in living systems. The only exception is a benz-8-carboline derivative, cryptolepine (78). Two alternative biogenetic... 

The yellow colored, sparcely soluble 5-ethyl-2-methyl-l l/f-pyrido[3,4-u] carbazolium 347 isolated from Aspidosperma gilbertii exists as a hydroxide after filtration of the corresponding iodide over basic aluminum oxide. A short synthesis was described (80CB3245). The Pyrido[3,4-a]carbazole ring system is present in the alkaloid AG-1, whereas Cryptolepine (348) possesses the indolo[3,2-b]quinoline moiety (65MI1). 

Dassonneville L, Lansiaux A, Wattez N, et al. Cytotoxicity and cell cycle effects of the plant alkaloids cryptolepine and neocryptolepine relation to drug-induced apoptosis. J Nat Prod 2001 64 134-135. 

Since natural product cryptolepine hydrochloride 173 (Fig. 48) has been found to be cytotoxic to B16 melanoma cells with an IC50 of 0.3 pg/mL (1.3 pM) [102], there has also been interest in cationic 5-carboline-based compounds as antitumor agents. For example, Wright and coworkers synthesized a series of these compounds and evaluated their activity against MAC 15 cells (murine adenocarcinomas of the colon) [103]. Of the compounds prepared, the most active was 179 which had an IC50 value of 1.03 pM. 

This as yet unidentified plant has yielded a small amount of a potently active compound in the 1138 yeast bioassay this has been submitted to the National Cancer Institute for bioassay in the 60-cell line assay. The active material has been identified as the known alkaloid cryp-tolepine (30) cryptolepine had an IC50 value of 5.8 fig/ml in the M109 cytotoxicity assay. 

In 1957, this approach was applied for the first time simultaneously by Mayer,4 Boyd,5 and Los, Saxena, and Stafford6 to an extensive group of heterocyclic compounds that can be considered analogs of the aromatic hydrocarbons of the azulene series.7,8 To express the general relationship among these compounds, they were classified by the term pseudoazulenes. Even then a number of such products existed,1 -9 36 but correlations involving this classification were not made. Instead, the investigation of these compounds was predominantly stimulated by the fact that the alkaloids sempervirine, alstonine, serpentine, and cryptolepine have pseudoazulene-type structures. 

The structure of the isomer obtained on soda lime distillation is uncertain, but it is probably best formulated as XXX, since its spectrum is closely similar to that of quindoline. Cryptolepine has a significant hypotensive activity, and has been reported to cause a marked and prolonged fall in blood pressure in dogs (139, 140). 

Cryptolepine [root] Cryptolepis sanguinolenta, DNA (intercalation) (TOPII)... 

Cryptolepine (Ranunculaceae) Cryptolepis sanguinolenta, TOPII (formation of cleavable... 

Fig. 1. HMQC spectrum of a 12 pig (0.05 pmol) sample of the indoloquinoline alkaloid cryptolepine (1) dissolved in 145 pL of d6-DMSO. The data were recorded overnight (16 h) at 500 MHz using a 3 mm micro-inverse-detection NMR probe.6 Both a proton reference spectrum (top trace) and the projection through the Fi frequency domain (bottom trace) are shown above the contour plot. (Reprinted with permission from Ref. 6. Copyright 1992, American Chemical Society and American Society of Pharmacognosy.)...

To illustrate the effects of shrinking the tube volume, Fig. 3 shows a series of three NMR tubes, each containing 1 pmol of the deep violet-colored indoloquino-line alkaloid cryptolepine (1). Each of the tubes shown, 5, 3, and 1.7 mm, has the sample of the alkaloid dissolved in what would be the nominal volume for that tube format. As is readily seen from simple inspection of the photograph shown in Fig. 3, the color of the solution in the three tubes goes from a light pink-violet color in the 5 mm tube, to violet in the 3 mm tube, and finally to nearly black in the 1.7 mm tube because of the concentration of the intensely colored alkaloid. 

Fig. 3. Photograph showing 5, 3, and 1.7 mm NMR tubes each containing 1 pmol of the deep violet-colored indoloquinoline alkaloid cryptolepine (3).

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