Cytotoxic sesquiterpene alkaloids

Fig. (17). Cytotoxic sesquiterpenes alkaloids from Maytemts emarginate...

Kuo YH,Chen CH, Kuo LM, King ML, Wu TS, Haruna M, Lee HK. Antitumor agents 112. Emarginatine B, a novel potent cytotoxic sesquiterpene pyridine alkaloid from Maytenus emarginata. J. Nat. Prod. 1990 53 422-428. 

In the course of these research programmes, cytotoxic quinones, polyester sesquiterpenes and pyridine-sesquiterpene alkaloids with antifeedant and/or insecticidal properties have been isolated from Latin American species, in particular those of the Maytenus genus which is extensively used by rural communities and tribes in the Andes and the Amazon basin. Recently some sesquiterpene alkaloids with immunosuppressive activity and sesquiterpenes with antitumoral activity have also been described [3]. 

The sesquiterpene pyridine alkaloids have antifeedant and insecticidal activ-ihes. Some alkaloids, such as triptonine B, hypoglaunine B, hyponine B and wilfortrine, have antivirus activity potential. Others, such as emarginatines A-B, E-G and emarginatine, have cytotoxic activity. Ebenifoline and cangorinine have immunosuppressive activity. 

Kuo YH, King ML, Chen CF, Chen HY, Chen CH, Chen K, Lee HK. Two new macrohde sesquiterpene pyridine alkaloids from Maytenus emarginata emarginatine G and the cytotoxic emarginatine F. J. Nat. Prod. 1994 57 262-269. 

A series of sesquiterpene evoninoate alkaloids have been isolated from the liana Hippocratea excelsa (Hippocrateaceae) from Mexico (Mata, 1993 Mata et al., 1990). This plant, called cancerina, is used medicinally to treat skin ailments and for its pesticidal properties. The main alkaloid, hippocrateine I (21), was cytotoxic in the 9 PS system (ED50 1.85 X 10 xg/ml) (Mata et al., 1990). This plant also contains small amounts of the antitumor triterpene tingenone (see Chapter 23). 

Among other antineoplastic agents of plant origin, the narcissus alkaloid pseudolycorine (22) is active against Rauscher leukemia.136 Taxol, from Taxus brevifolia, is active against a number of experimental neoplastic systems its structure (23) was reported.The sesquiterpene lac-tonesl38,139 and bufadienolidesl are cytotoxic. 

The factor responsible for cytotoxicity of the sesquiterpene lactones is the 0=C-( i=CH2 moiety. 38 Total synthesis of the tumor-inhibitory apor-phine alkaloids, thalicarpine (24) and hernandallne was accomplished. 

An tmusual association between a sesquiterpene and a purine was isolated from Suhergorgia suherosa, a species of Chinese origin. The sesquiterpenic part of this atypical alkaloid has the carbon skeleton of quadrane (see below), and this derivative is slightly cytotoxic for the cell line MDA-MB-231 (breast cancer). 

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