Showing papers in "ChemInform in 1998"

Insertion Electrode Materials for Rechargeable Lithium Batteries

Abstract: The performance and safety of rechargeable batteries depend strongly on the materials used. Lithium insertion materials suitable for negative and positive insertion electrodes are reviewed. Future trends, such as alternative materials for achieving higher specific charges are discussed. (orig.) 1041 refs.

Pitting Corrosion of Metals. A Review of the Critical Factors

Abstract: Pitting corrosion is localized accelerated dissolution of metal that occurs as a result of a breakdown of the otherwise protective passive film on the metal surface. This paper provides an overview of the critical factors influencing the pitting corrosion of metals. The phenomenology of pitting corrosion is discussed, including the effects of alloy composition, environment, potential, and temperature. A summary is then given of studies that have focused on various stages of the pitting process, including breakdown of the passive film, metastable pitting, and pit growth.

Podophyllotoxins: Current Status and Recent Developments

Abstract: Podophyllotoxin is a natural product isolated from Podophyllum peltatum and Podophyllum emodi and has long been known to possess medicinal properties. Etoposide (VP-16), a podophyllotoxin derivative, is currently in clinical use in the treatment of many cancers, particularly small cell lung carcinoma and testicular cancer. This compound arrests cell growth by inhibiting DNA topo-isomerase II, which causes double strand breaks in DNA. VP-16 does not inhibit tubulin polymerization, however, its parent compound, podophyllotoxin, which has no inhibitory activity against DNA topoisomerase II, is a potent inhibitor of microtubule assembly. In addition to these two mechanisms of action, an unknown third mechanism of action has also been proposed for some of the recent modifications of podophyllotoxins. Owing to its severe toxic side effects a number of modifications have been done on podophyllotoxin structure. Some of the congeners exhibited potent antitumor actiivity, of which etoposide and teniposide are in clinical use, NK 611 is in phase II clinical trials and many compounds are in the same line. Recent developments on podophyllotoxins have led structure-activity correlations which have assisted in the design and synthesis of new podophyllotoxin derivatives of potential antitumor activity. Modification of the A-ring gave compounds having significant activity but less than that of etoposide, whereas modification of the B-ring resulted in the loss of activity. One of the modifications in the D-ring produced GP-11 which is almost equipotent with etoposide. E-ring oxygenation did not affect the DNA cleavage which led to the postulation of the third mechanism of action. It has also been observed that free rotation of E-ring is necessary for the antitumor activity. The C4-substituted aglycones have a significant place in these recent developments. Epipodophyllotoxin conjugates with DNA cleaving agents such as distamycin increased the number of sites of cleavage. The substitution of a glycosidic moiety with arylamines produced enhanced activity. Modification in the sugar ring resulted in the development of the agent, NK 611 which is in clinical trial at present. This article review, the progress of podophyllotoxins from its early applications in folk medicine to the most recent modifications and the mechanism(s) of action, pharmacology and the structure-activity relationships.

Protein Folding: A Perspective from Theory and Experiment

Abstract: The mechanism of protein folding (represented schematically below) is one of the most fascinating problems in the field of chemical reactions. This review presents the progess made recently in understanding key elements of this reaction and describes a solution to the often quoted Levinthal Paradox.

Tubulin as a Target for Anticancer Drugs: Agents which Interact with the Mitotic Spindle

Abstract: Tubulin is the biochemical target for several clinically used anticancer drugs, including paclitaxel and the vinca alkaloids vincristine and vinblastine. This review describes both the natural and synthetic agents which are known to interact with tubulin. Syntheses of the more complex agents are referenced and the potential clinical use of the compounds is discussed. This review describes the biochemistry of tubulin, microtubules, and the mitotic spindle. The agents are discussed in relation to the type of binding site on the protein with which they interact. These are the colchicine, vinca alkaloid, rhizoxin/maytansine, and tubulin sulfhydryl binding sites. Also included are the agents which either bind at other sites or unknown sites on tubulin. The literature is reviewed up to October 1997. © 1998 John Wiley & Sons, Inc., Med Res Rev, 18, No. 4, 259–296, 1998.

Chemical, Biological and Clinical Aspects of Dexrazoxane and Other Bisdioxopiperazines

Abstract: The bisdioxopiperazine dexrazoxane (ICRF-187) has proven to be clinically very effective in reducing the cardiotoxicity of doxorubicin and other anthracyclines. Doxorubicin is thought to exert its toxicity through iron-based oxygen free radical-induced oxidative stress on the relatively unprotected cardiac muscle. Upon hydrolysis, dexrazoxane forms a compound similar to ethylenediaminetetraacetic acid (EDTA) which, like EDTA, is a strong chelator of iron. Dexrazoxane presumably exerts its cardioprotective effects by either binding free or loosely bound iron, or iron complexed to doxorubicin, thus preventing or reducing site-specific oxygen radical production that damages cellular components. The chemistry, biochemistry, and cell biology of dexrazoxane and other bisdioxopiperazines are discussed. The pre-clinical studies demonstrating the protective effects of dexrazoxane against toxicities caused by doxorubicin, other anthracyclines, bleomycin, alloxan, acetaminophen, and oxygen are also discussed. In vitro and in vivo studies of the cardioprotective and other effects of other bisdioxopiperazines are also covered. Also discussed are the anti-metastatic and radiosensitization effects of razoxane and dexrazoxane. The current clinical status of dexrazoxane in preventing anthracycline-induced toxicities in both adult and pediatric patients are reviewed

Structural Basis for Cyclic Terpene Biosynthesis by Tobacco 5‐epi‐Aristolochene Synthase

Abstract: Terpene cyclases catalyze the synthesis of cyclic terpenes with 10-, 15-, and 20-carbon acyclic isoprenoid diphosphates as substrates. Plants have been a source of these natural products by providing a homologous set of terpene synthases. The crystal structures of 5-epi-aristolochene synthase, a sesquiterpene cyclase from tobacco, alone and complexed separately with two farnesyl diphosphate analogs were analyzed. These structures reveal an unexpected enzymatic mechanism for the synthesis of the bicyclic product, 5-epi-aristolochene, and provide a basis for understanding the stereochemical selectivity displayed by other cyclases in the biosynthesis of pharmacologically important cyclic terpenes. As such, these structures provide templates for the engineering of novel terpene cyclases.

Stability and Structural Features of the Duplexes Containing Nucleoside Analogues with a Fixed N‐Type Conformation, 2′‐O,4′‐C‐Methyleneribonucleosides.

Abstract: Bicyclic nucleoside analogues with a fixed N-type conformation, 2′-O,4′-C-methyleneuridine and -cytidine, were incorporated into oligonucleotides, and the binding efficiency of the modified oligonucleotides to the complementary DNA and RNA as well as the CD spectra of the modified DNA-DNA and modified DNA-RNA duplexes were studied.

Capacity Fade Mechanisms and Side Reactions in Lithium‐Ion Batteries

Abstract: The capacity of a lithium‐ion battery decreases during cycling. This capacity loss or fade occurs due to several different mechanisms which are due to or are associated with unwanted side reactions that occur in these batteries. These reactions occur during overcharge or overdischarge and cause electrolyte decomposition, passive film formation, active material dissolution, and other phenomena. These capacity loss mechanisms are not included in the present lithium‐ion battery mathematical models available in the open literature. Consequently, these models cannot be used to predict cell performance during cycling and under abuse conditions. This article presents a review of the current literature on capacity fade mechanisms and attempts to describe the information needed and the directions that may be taken to include these mechanisms in advanced lithium‐ion battery models.

Potent and Selective Inhibitors of the Proteasome: Dipeptidyl Boronic Acids.

Abstract: Potent and selective dipeptidyl boronic acid proteasome inhibitors are described. As compared to peptidyl aldehyde compounds, boronic acids in this series display dramatically enhanced potency. Compounds such as 15 are promising new therapeutics for treatment of cancer and inflammatory diseases.

Selective Estrogen Receptor Modulators (SERMs)

Abstract: Naturally occurring estrogens, such as 17 beta-estradiol and estrone, have traditionally been thought to play a central role in the development and maintenance of the female reproductive system and secondary sexual characteristics. In recent years, their beneficial effects on the skeleton, the cardiovascular system, and the central nervous system, as well as the cancer risks associated with long term exposure have also been recognized. The widespread use of "antiestrogens" such as tamoxifen for the prevention and treatment of breast cancer has revealed that such compounds, while functioning as estrogen antagonists in mammary tissue, actually mimic the effects of estrogen in other tissues. The search for more selective agents has led to the development of raloxifene, a Selective Estrogen Receptor Modulator, which functions as an estrogen antagonist in the breast and uterus and as an estrogen agonist in the skeleton and cardiovascular system. Recent progress in the development of SERMs is the subject of this review, with an emphasis on structure activity relationships and on their effects in non-traditional target tissues.