Of bruceoside

TLC) of a chloroform soluble fraction of B. antidysenterica revealed the presence of spots differing from those previously isolated by Kupchan et al [2] Two of these spots showed Rf values slightly higher than those of bruceoside-A (9) and -B (10). Isolation of these two compounds by column chromatography (CC) on silica gel, followed by further... 

Hall IH, Lee KH, Eigebaly SA, Imakura Y, Sumida Y, Wu RY (1979) Antitumor agents. XXXIV Mechanism of action of bruceoside A and brusatol on nucleic acid metabolism of P-388 lymphocytic leukemia cells. J Pharm Sci 68 883... 

Quassinoids —The antileukaemic activity of some quassinoids has revived interest in this group. Three new biologically active compounds have been isolated. Quassimarin (118) occurs in Quassia amara with the inactive simalikalactone D (129) 86 Bruceoside A, from Brucea javanica, is the glucoside (120). The third... 

Bruceosides D (98), E (99), and F (100) show selective cytotoxicity in the leukemia and non-small cell lung, colon, CNS, melanoma, and ovarian cancer cell lines with log GI50 values in the range of-4.14 to -5.72 [46],... 

In recent literature [101] the synthetic compound 3,15-di-O acetylbruceolide (230), a derivative from bruceoside showed a potent in vitro antimalarial activity against Plasmodium falciparum equivalent to that of chloroquine (225) [102] and also a potent in vivo activity against Plasmodium berghei in mice, with low cytotoxicity against mouse mammary tumor, representing a model in the same host. 

Bruceoside-B (231), as well as yadanzioside-B (77) and -L (96), showed good EC50 values of 3,5, and 5 pM, respectively. However, their therapeutic indexes (TI) of 1, 0.8, and 2, respectively, indicate that they are toxic as anti-HIV agents. 

Three new quassinoid glucosides, bruceoside-D (37), -E (38), and -F (39) were isolated from the same plant, and their structures were elucidated by spectral evidence and chemical transformation to known compounds. Bruceoside-D (37), -E (38), and -F (39) were evaluated for cytotoxicity in the NCI s in vitro human tumor cell line panel, which included 58 cell lines representing nine cancer types. These compounds showed selective cytotoxicity in cell lines of leukemia, non-small cell lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, renal cancer, prostate cancer, and breast cancer. The log GI50 values (log concentration which reduced cell growth to 50%) ranged from >-4 to -5.72, as shown in Table 2 [18]. 

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). 

Okano and Lee (73) converted the quassinoid glycoside bruceoside-A (64) to bruceantin (53). The methods used involved selective hydrolysis of the ester and glycosyl groups followed by esterification of the hydroxyl at position 15. 

---