Apoptotic activity

Isoxazolines are partially unsaturated isoxazoles. In most cases these compounds are precursors to the isoxazoles, and as a result, the synthesis can also be found in Sect. 3.2.1b. Kaffy et al., used a 1,3-dipolar cycloaddition of a nitrile oxide (186) with the respective styrene (201a or b) to generate isoxazolines (202a or b, respectively). Depending on the substitution of the vinyl portion of the styrene molecule, either 3- or 4-substituted isoxazolines could be formed (Scheme 55) [94], Simoni et al. employed similar chemistry to produce isoxazolines [60]. Kidwai and Misra emplyed microwave technology to treat chalcones with hydroxylamine and basic alumina [99]. The isoxazoles synthesized by Simoni et al. possess anti-proliferative and apoptotic activity in the micromolar range [60]. 

Tseng SC, Kruse FE, Merritt J, Li DQ. Comparison between serum-free and fibroblast-cocultured single-cell clonal culture systems Evidence showing that epithelial anti-apoptotic activity is present in 3T3 fibroblast-conditioned media. Curr Eye Res 15 973-984 (1996). 

Jeeeord, C. E., etal., Nudear-cytoplasmic translocation of BARDl is linked to its apoptotic activity. Oncogene, 2004, 23(20), 3509-20. 

Maccarrone M, PauseUi R, di Rienzo M, Finazzi-agro A, Binding, degradation and apoptotic activity of stearoylethanolamide in rat C6 ghoma cells, Biochem J 366 137-144, 2002. 

Cai YJ, Wei QY, Fang JG, Yang L, Liu ZL, Wyche JH. 2004. The 3,4-dihydroxyl groups are important for trans-resveratrol analogs to exhibit enhanced antioxidant and apoptotic activities. Anticancer Res 24 999-1002. 

T. Nakashima, M. Miura, and M. Hara, Tetrocarcin A inhibibits mitochondrial function of Bcl-2 and suppresses its anti-apoptotic activity, Cancer Res., 60 (2000) 1229-1235 and references therein. 

Three different pharmacodynamic principles of action can be distinguished for mAbs, comprising lysis or apoptotic activity, coating activity, and inactivating activity (see Section 3.5.2), depending on the type of antigen and the antigen-antibody interaction. 

Members of the Bcl-2 family share one or more Bcl-2 homology (BFI) domains, named BFI1, BFI2, BFI3, and BFI4 (Adams and Cory, 1998). It is not yet clear which structural features determine if these proteins possess pro- or anti-apoptotic activities. However, some studies revealed that the BH3 domain is a critical domain for the proapoptotic members (Chittenden et al., 1995). Besides BH domains, some contain a hydrophobic domain in the C-terminal region, which is essential for the attachment to intracellular membranes, like the outer mitochondrial, nuclear, and endoplasmic reticulum membranes (Krajewski et al., 1993 Nguyen et al., 1993). 

Zha J, Harada H, Osipov K, Jockel J, Waksman G, Korsmeyer SJ (1997), BH3 domain of BAD is required for heterodimerization with BCL-XL and pro-apoptotic activity, J. Biol. Chem. 272 24101-24104. 

Chloptosin (111) [90] also containing unusual amino acids was found to exhibit apoptotic activity against human adenocarcinoma. 

Eudesmanolide sesquiterpene lactones (G6 G6 C40L) include a variety of variously cytotoxic compounds. The antifeedants alantolactone and isoalantolactone (helenin being a mixture of the two) (C6 ] C5 C40L=CH2) are antimicrobial. The pro-apoptotic activity of these compounds may derive from the reactivity of the a-methylene-y-butyrolactone ring... 

Activation domain 2 (AD2), important for apoptotic activity residues 43-63. 

Prohne-rich domain, important for the apoptotic activity of p53 residues 80-94. 

Chai J, Du C, Wu JW, Kyin S, Wang X, Shi Y (2000) Structural and biochemical basis of apoptotic activation by Smac/DIABLO. Nature 406 855-862... 

Vucic D, Deshayes K, Ackerly H, Pisabarro MT, Kadkhodayan S, Dixit VM. SMAC negatively regulates the anti-apoptotic activity of melanoma inhibitor of apoptosis (ML-lAP). J. Biol. Chem. 2002 277 12275-12279. 

Reaction of amino diols with a fatty acid afforded a series of simple ceramide analogs with pro-apoptotic activity in human cancer cell lines (160). An example is Ai-oleoylserinol, which induced apoptosis in cells expressing the pro-apoptotic protein PAR-4 and was used to purge transformed cells from embryonic stem cells before implantation into mouse brain (161). 

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