Cryptolepine alkaloids

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. 

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. 

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).

Fig. 4. Spectra acquired for a 0.55 pmol sample of the indoloquinoline alkaloid cryptolepine (1) dissolved in 25 pL J6-DMSO. (a) Proton-carbon (HMQC) direct correlation spectrum recorded in 12m (16 x 2048 point files, 16 transients/ increment) shown with no linear prediction, (b) Long-range 1H-13C HMBC spectrum of the same sample optimized for 8 Hz. The data were acquired as 64 x 4096 files with 16 transients accumulated/ increment. Data are again shown without any linear prediction. (Reprinted with permission from Ref. 11. Copyright 1998, John Wiley Sons, Ltd.)...

Hyoscyamine, scopolamine, and other tropane alkaloids (AA) acetylheliosupine and some other pyrrolizidine alkaloids arecoline (A) berbamine, berberine, and other isoquinoline alkaloids dicentrine and other aporphine alkaloids strychnine, brucine cryptolepine (AA) sparteine and other quinolizidine alkaloids (A) pilocarpine (A) emetine himbacine and other piperidine alkaloids (A) imperialine (AA) muscarine (A)... 

The authors have also extensively studied the indoloquinoline families of alkaloids related to cryptolepine (indolo[3,2-fo]quinoline 57), applying direct and long-range... 

Cryptolepine (57), the parent alkaloid in the series, was studied in 1996 using long-range GHMBC data [83]. In order to observe a correlation to the N-10... 

Most of the compounds isolated from C. sanguinolenta are alkaloids and are analogs of indolo[3,2-f)]quinoline 11). The major alkaloidal component of the plant is cryptolepine (72). In addition to cryptolepine, comparatively small quantities of a number of related alkaloids have been isolated from the plant These include 11-hydroxycryptolepine, cryptoheptine, isociyptolepine, quindoline, bisciyptolepine, ciyptoquindoline, cryptolepicarboline, cryptospirolepine. Quindolinone, cryptotakienine, and cryptomisrine 11,13-16) (Figure 1). 

Cryptolepine (170), an indole alkaloid with an obscure structural relationship to tryptophan, was shown to be the major alkaloid of Sida acuta L. (Malvaceae) (102). 

Seven monoindole Strychnos alkaloids, namely matadine (35), serpentine (36), alstonine (39), melinonine F (40), normelinonine F (41), 5,6-dihydroflavopereirine (42) and strychnoxanthine (43) as well as the hemisynthetic Nb-methyharmalane, together with cryptolepine (37) as reference compound, were tested for their in vitro antiplasmodial activity... 

Fig.(7). Structure of Strychnos monoindole alkaloids evaluated for their anticancer and/or antiprotozoal acrtivites. Structure of cryptolepine and ellipticine are given for comparison purpose.

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