Cytotoxicity profile

In this chapter we show that topi inhibitors with apparently similar cytotoxic profile could have a specific effect of cell cycle, distinguishing the activity of classical camptothecin, such as irinotecan and SN-38, active specifically on the S phase by edotecarin active as tight binder on topi and without cell cycle specificity. The use of cytometry of solid tumors from xenograft made it possible to provide support to immunohistochemical analysis during the study of biomarkers, comparing cell cycle effects to topi modulation after treatment. 

Halomon (60) and related antitumor monoterpenes 61-63 from the Philippinian red alga Portieria hornemannii display a unique differential cytotoxicity profile against the NCI s panel of 60 human tumor cell lines,... 

Fuller RW, Cardellina IIJH, Kato Y, Brinen LS, Clardy J, Snader KM, Boyd MR (1992) A Pentahalogenated Monoterpene from the Red Alga Portieria hornemannii Produces a Novel Cytotoxicity Profile Against a Diverse Panel of Human Tumor Cell Lines. J Med Chem 35 3007... 

This review deals with the syntheses of various hyperbranched polyamines that are prepared through a one-step polymerization process. Furthermore, we present the current status of polyamines as gene carriers and describe their versatility, and their properties such as structure-property dependency, gene transfection efficiency, and cytotoxicity profiles of hyperbranched polyamines. 

Keywords Applications Cytotoxicity profile Gene delivery Hyperbranched polyamines Poly(amido amine) Poly(amido ester) Poly(ethylene imine) Polyglycerol amines Structure-property dependence Synthesis Transfection efficiency... 

To assess the cytotoxic profile of 1, the effect of different concentrations of decitabine on colony formation in the human cell lines MDA-MGB-231, Calu-6, and DU-145 were observed (Table 2). The CC50 (50% cytotoxic concentration) values of 1 for MDA-MB-231, Calu-6, and DU-145 were 50 ng/mL. 

Xia, M. et al. 2008. Compound cytotoxicity profiling using quantitative high-throughput screening. Envir. Health Perspect. 116, 284—291. 

Peloruside A 14 (Scheme 6.1 Part 2) was isolated from a New Zealand Mycale hentschei marine sponge and initially showed activity against P388 murine leukaemia cells at 10 ng/mL.98 Peloruside s cytotoxicity profile and structural similarity to bryostatin led to the examination of protein kinase C (PKC) as a possible mode of action.242 This was determined to be incorrect and it was soon established that the remarkable activity of peloruside was through the stabilisation of microtubules at a site distinct from the taxoid site.243... 

Xia M, Huang R, Witt KL, Southall N, Fostel J, Cho MH, Jadhav A, Smith CS, Inglese J, Portier CJ, Tice RR, Austin CP. Compound cytotoxicity profiling using quantitative high throughput screening. Environ. Health Perspect. 2008 116 284-291. 

DLD-1) and A2780 cells (see Fig. 1). In both cell lines, fluorescence was observed to be predominantly localized within lysosomes after 1-, 4-, and 24-hour incubations with the complex, with no colocalization with mitochondrial and nucleic acid fluorescent probes. These results were in conflict with the high cytotoxicity profile observed for the platinum complex and cellular uptake smdies that showed high platinum content within the nucleus after 4 hour incubations (65). Several possible reasons exist for the lack of fluorescence detected in the nucleus. 

Comparative evaluation of 1 and cephalostatins 14 and 15 (14, 15) in the NCI in vitro primary screen again revealed a reduced average GI50 cytotoxicity (100 nM and 68 nM respectively) for 14 and 15 compared to 1 [23]. The final pair of cephalostatins (16 and 17) isolated from C. gilchristi exhibited the same cytotoxic profile as the majority of the other cephalostatins with the panel averaged GI50 values of 16 (InM) and 17 (4nM) comparable to that of 1 (InM) [24],... 

Each component drug must have an altogether different mechanism of cytotoxic profile and, preferably, command phase specificity. 

The activity of these analogues against the two cell line panels is shown in Tables 1 and 2. The compounds exhibited a cytotoxicity profile similar to cisplatin against the primary cell line panel with the HT1376 bladder carcinoma line being the most sensitive. Interestingly, in the ovarian cell line panel the compounds were equally active against the CHl/CHl-R sensitive/resistant pair . 

The interest of PG nanogels spearheads from their nontrivial synthesis into their biological implications. For example, nanogels with sizes between 25 and 350nm have been shown to rapidly internalize into cell, with a preferred localization in the perinuclear region. As shown in Figure 6.12, there is evidence for a size-dependent endocytotic mechanism of ceU entry. In addition, such PG gel architectures afforded a safe cytotoxicity profile in the mg/ml range [27]. 

Until now, carbosilane dendrimers have the best cytotoxicity profile, and also present an added value, since they can function in media containing serum and antibiotics, while the use of Lipofectintrade (a common reagent used for in vitro transfection in laboratories) is required to remove these additives. This is a fundamental advantage that will allow carbosilane dendrimers to make the transition to in vivo scenarios. 

The R substituent modulates aqueous solubility and biological compatibiUty in the Fe(II) complexes [(q -CsH4R)Fe(CO)2X]. They have long half-fives (Mb assay) and excellent cell viability and cytotoxicity profiles [130]. They were not studied in vivo but the parent [(q5-C5H5)Fe(CO)2Cl] proved very toxic to mice (MTD<8.5 mg/kg i.p.), causing convulsive death 3 min after i.p. administration (AUama Lda, unpublished results (2013)). [(CsH4Me)Mn(CO)3 has a similar toxicity, which is hard to relate to CO loss and may be structure dependent [131]. 

Nafee N, Schneider M, Schaefer U et al (2009) Relevance of the colloidal stability of chitosan/PLGA nanoparticles on their cytotoxicity profile. Int J Pharm 381 130-139... 

Nafee et al. explored significance of the colloidal stability of chitosan/PLGA NPs on their cytotoxicity profile. It has been observed that chitosan/PLGA NPs enhances the colloidal stability and induced potential cytotoxicity effects [304]. 

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