Cytotoxicity in HELA

The mode of action of the harringtonines has been investigated. All inhibit protein synthesis in eukaryotic cells (190-192). The principal effect of harringtonine was inhibition of protein biosynthesis in HeLa cells (193). Homoharringtonine, a potential antineoplastic alkaloid (191), was cytotoxic in HeLa, KB, and L cells growing in monolayer cell cultures (194). 

Saponins have been considered toxic for different organisms. Meyer et ah (1990) found toxicity to brine shrimp. Woldemichael and Wink (2001) found monodesmoside saponins hemolytically active. The hemolysis may be produced by the interaction of the saponins with membranes, producing pores that lead to rupture of the (Seeman et ah, 1973). Kuljanabhagavad et ah (2008) described mainly saponins with an aldehyde group as cytotoxic in HeLa (cervix adenocarcinoma) cell line. 

MWNTs were found to be cytotoxic in human skin fibroblasts (HSF42) and human epidermal keratinocytes (HEK) [42-44], whereas SWNTs were toxic in human keratinocyte (HaCaT) cultures [25, 26, 45]. Reduced cell proliferation and oxidative stress were reported also in epithelial (HeLa) cells [45] and murine epidermal cells (JB6 P + ) [46] upon incubation with SWNTs. 

Cytotoxic to HeLa cells in vitro no significant antibacterial activity 360... 

Leighton et al. used chiral allylsilane and crotylsilane reagents to synthesize two key intermediates, 48 and 50, in the total synthesis of dolabelide D (45), a 24-membered macrolide with cytotoxicity against HeLa-S3 cells26 (Scheme 3.2w). Asymmetric allylation of the aldehyde 46 with the chiral reagent (S,S)-27... 

The potency of the 3 -amino-4 -dimethylamino analogue against a panel of tumor cell lines (P-388, A-549, HT-29, MEL-28 or HeLa, HI 16, H-60) is even higher than that of Combretastatin A-4 or the related 3 -amino analogue. It is remarkable that this derivative, which is the most cytotoxic, has no effect on tubulin polymerization at concentrations below 30 )iM. This fact is in contrast to the usual behaviour of other combretastatin analogues, which always display a strong inhibitory effect on tubulin polymerization whenever they are cytotoxic in the submicromolar range. 

The cytotoxicity of distamycin derivatives was estimated on the basis of the morphological modifications induced in HeLa cell cultures, after incubation for 40 h in Hanks saline solution + 0.5 % lactalbumin hydrolysate + 5 % calf serum (HLS). Assay on vaccinia virus Cultures of HeLa cells (grown in HLS medium) or mouseembryo cells (grown in HLS medium plus 0.1 % yeastolate) infected with vaccinia virus (Strain WR/ATCC) were used. Preliminary assays were made according to Herrmann et al.° Subsequent studies were carried out by assessing the inhibition of plaque formation (ECP) as well as the inhibition of infectious virus production in test tube cultures treated with the compounds for 40 h after the absorption of the virus. 

Different cell types exhibit different sensitivities to ricin in vitro. For example, the concentration of ricin in tissue culture medium that leads to an approximately 50% inhibition of protein synthesis is 13-22 pM for human lymphoma (Daudi cells), AKR/A, lipopolysaccharide blasts, or mice spleen cells, but it is 0.4 pM for nonparenchymal rat liver cells (Fulton et al., 1986). Ricin causes cytotoxicity in cultured human HeLa cells at concentrations as low as 15 pM (Eiklid et al., 1980 Rao et al., 2005), with an approximately 50% loss of viable cells occurring after a 12 h exposure to... 

Rhamnopiericidin Ai (41) was isolated from Streptomyces sp SN-198 and its structure was determined by UV, IR, FABMS, one- and two-dimensional and 13c NMR, and acid hydrolysis to give rhamnose [156]. 3 -Rhamnopiericidin Ai was cytotoxic to HeLa and KB cells in vitro, with IC50 = 2.8 pg/ml and 0.74 pg/ml, respectively. Unlike the glucopiericidins, 41 was generally less active as an antimicrobial agent than 37 [156]. 

Treatment with AS-6 caused a decrease in cholesterol levels [150, 151], but it is unclear whether this property relates to its ability to enhance insulin action on lipid metabolism or results from other actions. Although ascochlorin originally was associated with cytotoxic effects in HeLa cell cultures [ 143], chronic studies (10 weeks) in mice with AS-6 showed no effects on food consumption or toxic signs in liver [147]. 

---