Natural products inducer

Bubb MR, Senderowicz AMJ, Sausville EA, Duncan KLK, Korn ED (1994) Jasplakinolide, a Cytotoxic Natural Product, Induces Actin Polymerization and Competitively Inhibits the Binding of Phalloidin to F-Actin. J Biol Chem 269 14869... 

Bubb, M. R., Senderowicz, M. J., Sausville, E. A., Duncan, K. L. K., and Korn, E. D., Jasplakinolide, a cytotoxic natural product, induces actin polymerization and competitively inhibits the binding of phalloidin to F-actin, J. Biol. Chem., 269, 14869, 1994. 

The antiproliferative activity of eleutherobin is based on interaction with tubulin, as is known for epothilone and taxol. These natural products induce depolymerization of microtubules and thereby interrupt the division of cancer cells [2], From experiments with highly purified tubulin, it was possible to show that some eleuthesides as well as epothilone A induce tubulin aggregation comparable to that of paclitaxel, and are also promoted by microtubule-associated proteins or GTP [22], Furthermore, kinetic measurements indicate... 

Figure 3.10 The FKBP12 rapamycin FRB complex, (a) Structure of rapamycin. (b) A depiction of the natural-product induced interface between FKBP12 and FRB. Each structure contains two proteins, FRB (cyan) and FKBP12 (green) with a bound rapamycin (yellow), (c) A close-up of the natural product binding pocket. The images were developed from structure dataset 4fap, which is readily available from the Protein Data Bank.

Recently, Kosmin has shown that bistramide A is responsible for severing actin filaments and covalently modifying actin.183 These studies indicated that, while the spiroketal and amide units of the natural product induced rapid disassembly of F-actin in vitro, the enone subunit of bistramide A was able to initiate covalent modification of actin in vitro and in live cells. These results indicate that, while PKC5 may not be the primary target of the natural product, it plays a dual role by binding to and severing F-actin and covalently sequestering... 

Like TPX, the microbially derived HDAC inhibitor depudecin 4 was also isolated based on its ability to reverse the transformed cellular phenotype of tumor cells. This diepoxide-containing natural product induced a flat phenotype in Kj-ras-transformed NIH 3T3 cells and was further characterized as an HDAC inhibitor by its ability to induce the accumulation of acetylated histones [13]. Apicidin (APC) 3, a cyclic tetrapeptide HDAC inhibitor with... 

Manlena SK, SharmaSD, Katiyar SK (2006) Berberine, a natural product, induces G1-phase cell cycle arrest and caspase-3-dependent apoptosis in human prostate carcinoma cells. Mol Cancer Ther 5 296-308... 

A classic diagnostic use of such stereochemical requirements, due to Ruzicka, is the ring contraction induced in natural products containing the 4,4-dimethyl-5a-3 -ol system (94). The epimeric, axial 3a-alcohols (95) dehydrate without ring contraction. Barton suggested that it is necessary for the four reacting centers (hydroxyl, C-3, C-4, C-5) to be coplanar for ring contraction to occur, and this is only the case with the 3)5-alcohol. 

For more than two decades Woodward s total synthesis1 1 "d of chlorophyll a was in fact the only total synthetic approach to a chlorin. When, in the early eighties, new chlorin-type natural products were isolated from different biological sources, a systematic investigation of selective synthetic approaches leading to chlorins was induced.4... 

With the discovery and structure elucidation of bonellin (1) and factor I (2), both naturally occurring chlorins. the systematic investigation of total synthetic approaches leading to these natural products and other chlorins was induced.4... 

Loads applied on products induce tension, compression, flexure, torsion, and/or shear, as well as distributing the loading modes. The product s particular shape will control the type of materials data required for analyzing it. The location and magnitude of the applied loads in regard to the position and nature of such other constraints as holes, attachment... 

Camptothecin was discovered as an active anticancer drug isolated from the bark of Camptotheca acuminata. The anticancer activity of camptothecin was discovered in the 1960s by the National Cancer Institute (NCI) as part of a systematic effort to screen for novel anticancer agents derived from natural products. Monroe Wall and Mansuhk Wani identified the chemical structure of camptothecin. They also identified the chemical structure of taxol, again under the auspices of the NCI. Susan Hoiwitz was contracted by the NCI to elucidate the anticancer mechanisms of camptothecin. She found in the early 1970s that camptothecin induced DNA breaks and attested DNA and RNA synthesis. However, it is approximately 12 years later, only after DNA topo-isomerase I (Topi) had been identified in human cells, that Leroy Liu and his coworkers found that Topi was the cellular target of camptothecin [reviewed in [1]. 

Biocatalytic access to both antipodal sulfoxides was exploited in total syntheses of bioactive compounds, which is outlined in some representative examples. Biooxidation of functionalized dialkyl sulfides was utilized in the direct synthesis of both enantiomers of sulforaphane and some analogs in low to good yields and stereoselectivities (Scheme 9.27) [206]. This natural product originates from broccoli and represents a potent inducer of detoxification enzymes in mammalian metabolism it might be related to anticarcinogenic properties of plants from the cruciform family. All four possible stereoisomers of methionine (R = Me) and ethionine sulfoxides... 

Allylic alcohols can be converted to epoxy-alcohols with tert-butylhydroperoxide on molecular sieves, or with peroxy acids. Epoxidation of allylic alcohols can also be done with high enantioselectivity. In the Sharpless asymmetric epoxidation,allylic alcohols are converted to optically active epoxides in better than 90% ee, by treatment with r-BuOOH, titanium tetraisopropoxide and optically active diethyl tartrate. The Ti(OCHMe2)4 and diethyl tartrate can be present in catalytic amounts (15-lOmol %) if molecular sieves are present. Polymer-supported catalysts have also been reported. Since both (-t-) and ( —) diethyl tartrate are readily available, and the reaction is stereospecific, either enantiomer of the product can be prepared. The method has been successful for a wide range of primary allylic alcohols, where the double bond is mono-, di-, tri-, and tetrasubstituted. This procedure, in which an optically active catalyst is used to induce asymmetry, has proved to be one of the most important methods of asymmetric synthesis, and has been used to prepare a large number of optically active natural products and other compounds. The mechanism of the Sharpless epoxidation is believed to involve attack on the substrate by a compound formed from the titanium alkoxide and the diethyl tartrate to produce a complex that also contains the substrate and the r-BuOOH. ... 

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