Quassinoids antitumor

Gillin, F. D., and D. S. Reiner In vitro Activity of Certain Quassinoid Antitumor Agents against Entamoeba histolytica. Arch. Invest. Med. 13 (Suppl. 3), 43 (1982). 

Polyphenolic Compounds and Sesquiterpene Lactones 62.2.3 Antitumor Quassinoids... 

For a recent structure-activity relationship correlation of quassinoids as antitumor agents see M. Okano, F. Narihiko, K. Tagahara, H. Tokuda, A. Iwashima, H. Nishino and K-H. Lee, Cancer Lett. 1995, 94, 139. 

Fukamiya N, Okano M, Miyamoto M (1992) Antitumor Agents, 127. Bruceoside C, a New Cytotoxic Quassinoid Glucoside and Related Compounds from Brucea javanica. J Nat Prod 55 468... 

Ailantinol G (43) a quassinoid isolated from Ailanthus altissima was evaluated for its antitumor effects promotion against Epstein-Barr virus early antigen activation introduced by 12-0-tetradecanoylphorbol-13-acetate in Raji cells [25],... 

Quassia amara Wood is still widely used in traditional medicine and some quassinoids and quassinoid glycosides isolated from Quassia have received renewed attention due to their biological activity as potential antitumor agents [78]. 

Many quassinoids were isolated from Simaroubaceous plant to demonstrated antitumor activity, however, these compounds have not been subjected to a test yet for their antitumor promoting effects. 

Six quassinoids isolated from Eurycoma tongifolia Jack, were subjected to in vitro tests on anti-tumor promoting. The most active compound for inhibition of tumor promoter-induced Epstein-Barr virus activation was 14,15 p-dihydroklaineanone (136, ICso= 5pM) [109]. This inhibitory potential was much higher than quercetin (IC50" 23 pM) and p-carotene (ICjo- 30 pM), two common antitumor promoting natural agents [110],... 

ABSTRACT This review covers various bioactive quassinoids in Simaroubaceous plants, which show cytotoxic antitumor, anti-tumor-promoter (= inhibitor against TPA-induced EBV-EA activation), anti-HIV, anti-tuberculosis, insect antifeedant, and other biological activities. Stability of quassinoids, the preparation of their derivatives, and their biological activities are also discussed. 

In a previous paper [1], we reviewed the isolation of quassinoids, alkaloids, and fatty acids from Simaroubaceous plants during the period 1972-1988 and discussed their biological activities, such as antitumor, antimalarial, and anti-inflammatory agents as well as insect antifeedants, amoebicides, and herbicides. This review will add new quassinoids isolated from Simaroubaceous plants from 1988 onwards and their biological activities, for example, antitumor, anti-tumor-promotor (= inhibitor against TPA-induced EBV-EA activation), anti-HIV, anti-tuberculosis, and insect antifeedant activities. Furthermore, the stability of quassinoids, lower activities of degradation products, and the synthesis of fluorinated quassinoids are also described. 

The NCI in vitro primary disease-oriented antitumor screen was used to select and guide the fractionation of the organic and aqueous extracts of Cedronia granatensis. Two quassinoids, sergeolide (69) and isobrucein-B (5), were isolated, to which the screening panel cell lines exhibited up to a 1000-fold range of differential sensitivity, were isolated. The compounds typically produced ICso-level responses at concentrations of 10-5 - lO- M... 

The same assay was carried out for five semi-synthetic quassinoids, which were obtained by esterification of the C-15 OH group of desacetyl-isobrucein-B (124) as shown in Table 13. All ester derivatives showed higher antitumor promoting activity than that of the starting quassinoid, desacetyl-isobrucein-B (124). A compound containing a fluorinated aliphatic ester showed the highest potency [36]. 

From the correlated structures of 1, 86, and 22, it seems reasonable to assume that bruceantin (1) (ED5o=0.59 ig/ml) [1] might be converted to dehydrobruceantin (86) (EDso=1.0 (Xg/ml) [1] and 86 might further converted to bruceanic acid-A (22) (ED5o=4.16 fAg/ml) (the values in the parentheses are antitumor activity for KB cells) [12], Thus, on the basis of these data, the activity drops with degradation of the quassinoid. 

Camptothecin Derivatives Polyphenolic Compounds and Sesquiterpene Lactones Antitumor Quassinoids Flavonoid Derivatives Colchicine Derivatives Quinone Derivatives... 

Limonoids (Tetranortriterpenoids) Quassinoids (Decanortriterpenoids) Pentanortriterpenoids Chemosystematic Studies Biological Activity Antifeedant Activity Medicinal and Antitumor Properties Limonin in Orange Juice References... 

Several quassinoids are known to have antileukemic activity (Blasko and Cordell, 1988 Cordell, 1978 Polonsky, 1983). Only compounds with a C20 skeleton have antileukemic activity. Quassimarin (51) from Quassia amara and bruceoside A (52) from Brucea javanica and a series of other quassinoids from Brucea antidysenterica (all Simarou-baceae) (Fig. 25.12) are active in this regard. Bruceantin (53) has a high degree of antitumor activity in P-388, LE, LL and B16 tissue culture systems (Cordell, 1978). Six quassinoids from Simaba multiflora and Soulamea soulameoides were shown to be active against several mmor systems (Klocke et al., 1985). 

Liou YF, Hall IH, Okano M, Lee KH, Chaney SG (1982) Antitumor agents XLVIII Structure - activity relationships of quassinoids as in vitro protein synthesis inhibitors of P-388 lymphocytic leukemia tumor cell metabolism. J Pharm Sci 71 430-435... 

Moher ED, Reilly M, Grieco PA, Corbett TH, Valeriote FA (1998) Synthetic studies on quassinoids transformation of (-)-glaucarabolone into (-)-peninsularinone. In vivo antitumor evaluation of (-)-glaucarabolone, (-)-chaparrinone, and (-)-peninsularinone. J Org Chem 63 3508... 

Lumonadio L, Atassi G, Vanhaelen M, Vanhaelen-Fastre R (1991) Antitumor activity of quassinoids from Hannoa Idaineana. J Ethnopharmacol 31 59-65... 

The most interesting of the varied types of triterpenes from the point of view of biological activity are the quassinoids. They exhibit antiamoebic (353), antimalar-ial (1020), antimitotic (287), antitumor (59, 403, 950), and cytotoxicity (59, 821, 823) effects. Bruceantin, 29, is being developed as a potential cancer chemotherapeutic agent and is currently in Phase 1 clinical trials in the United States (950). 

Okano M, Lee KH, Hall IH, Boettner FE 1981 Antitumor agents. 39. Bruceantinoside-A and -B novel antileukemic quassinoid glucosides from Brucea antidysenterica. J Nat Prod 44 470-473... 

Studies of microbial transformations of bruceantin (53) led to the isolation of new analogs of this antitumor quassinoid (70). Thus, Streptomyces griseus (ATCC 10137) totally metabolized bruceantin (53) within 19 h, and a preparative scale incubation using bruceantin provided brucein C (51), bruceantin-4, 5 -epoxide and bruceantin-5 -ol. None of the metabolites were as active as bruceantin in the P388 test system (70). 

Wall, M. E., and M. C. Wani Plant Antitumor Agents. 17. Structural Requirements for Antineoplastic Activity in Quassinoids. J. Med. Chem. 21, 1186 (1978). 

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