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Promising Compounds (promising + compound)
Selected AbstractsSynthesis and In-Vitro Antitumor Activities of Some Mannich Bases of 9-Alkyl-1,2,3,4-tetrahydrocarbazole-1-onesARCHIV DER PHARMAZIE, Issue 3 2009Jing Chen Abstract A novel series of 2-substituted aminomethyl-9-alkyl-1,2,3,4-tetrahydrocarbazole-1-ones 5a,q was synthesized via aminomethylation of 9-alkyl-1,2,3,4-tetrahydrocarbazole-1-ones 4a,e with hydrochlorides of the respective amines 6a,m. The structures of these newly synthesized compounds were characterized by 1H-NMR, MS, and elemental analysis. All the compounds were tested for their cytotoxic activity in vitro against four human tumor cell lines including human non-small lung cancer cells (A549), human gastric adenocarcinoma (SGC), human colon cancer cell (HCT116), human myeoloid leukemia cells (K562), and one multi-drug resistant subline (KB-VCR). Most compounds showed moderate to potent cytotoxic activity against the tested cell lines. Preliminary mechanism research indicated that the most promising compound, 2-diethylaminomethyl-9-methyl-1,2,3,4-tetrahydrocarbazole-1-one 5c, exhibited a potential inhibitory effect against microtubule. [source] Small-Sample Inference for Incomplete Longitudinal Data with Truncation and Censoring in Tumor Xenograft ModelsBIOMETRICS, Issue 3 2002Ming Tan Summary. In cancer drug development, demonstrating activity in xenograft models, where mice are grafted with human cancer cells, is an important step in bringing a promising compound to humans. A key outcome variable is the tumor volume measured in a given period of time for groups of mice given different doses of a single or combination anticancer regimen. However, a mouse may die before the end of a study or may be sacrificed when its tumor volume quadruples, and its tumor may be suppressed for some time and then grow back. Thus, incomplete repeated measurements arise. The incompleteness or missingness is also caused by drastic tumor shrinkage (<0.01 cm3) or random truncation. Because of the small sample sizes in these models, asymptotic inferences are usually not appropriate. We propose two parametric test procedures based on the EM algorithm and the Bayesian method to compare treatment effects among different groups while accounting for informative censoring. A real xenograft study on a new antitumor agent, temozolomide, combined with irinotecan is analyzed using the proposed methods. [source] Synthesis, Cruzain Docking, and in,vitro Studies of Aryl-4-Oxothiazolylhydrazones Against Trypanosoma cruziCHEMMEDCHEM, Issue 9 2007Cristina, Lima Leite Prof. Abstract Research in recent years has demonstrated that the Trypanosoma cruzi cysteine protease cruzain (TCC) is a valid chemotherapeutic target. Herein we describe a small library of aryl-4-oxothiazolylhydrazones that have been tested in assays against T.,cruzi cell cultures. The docking studies carried out suggest that these compounds are potential ligands for the TCC enzyme. The most promising compound of this series, N -(4-oxo-5-ethyl-2,-thiazolin-2-yl)- N,-phenylthio-(Z)-ethylidenehydrazone (6,f), was shown to be very active at non-cytotoxic concentrations in in,vitro assays with mammalian cells and has a potency comparable with reference drugs such as nifurtimox (Nfx) and benznidazole (Bdz). [source] Synthesis and Biological Evaluation of Bicyclic Nucleosides as Inhibitors of M.,tuberculosis Thymidylate KinaseCHEMMEDCHEM, Issue 10 2006Daele, Ineke Van Abstract Herein we describe the synthesis and conformational analysis of a series of bicyclic thymidine derivatives and their evaluation as inhibitors of thymidine monophosphate kinase from Mycobacterium tuberculosis (TMPKmt), based on previously discovered bicyclic sugar nucleosides. With a Ki value of 2.3,,m, 1-[3-aminomethyl-3,5-dideoxy-2- O,6- N -(thiocarbonyl)-,- D -ribofuranosyl]thymine emerged as the most potent TMPK inhibitor of this series. Moreover, this promising compound displays inhibitory potency against Mycobacteria cultures with an IC99 value of 100,,g,mL,1, thus promoting TMPKmt for the first time as a validated target for further inhibitory design. Attempts to rationalise the observed structure,activity relationship (SAR) involving molecular modelling and conformational analysis are described. [source] Development and Testing of Energetic Materials: The Concept of High Densities Based on the Trinitroethyl FunctionalityADVANCED FUNCTIONAL MATERIALS, Issue 3 2009Michael Göbel Abstract The development of new energetic materials is an emerging area of materials chemistry facilitated by a worldwide need to replace materials used at present, due to environmental considerations and safety requirements, while at the same time securing high performance. The development of such materials is complex, owing to the fact that several different and apparently mutually exclusive material properties have to be met in order for a new material to become widely accepted. In turn, understanding the basic principles of structure property relationships is highly desirable, as such an understanding would allow for a more rational design process to yield the desired properties. This article covers the trinitroethyl functionality and its potential for the design of next generation energetic materials, and describes relevant aspects of energetic materials chemistry including theoretical calculations capable of reliably predicting material properties. The synthesis, characterization, energetic properties, and structure property relationships of several new promising compounds displaying excellent material properties are reported with respect to different kinds of applications and compared to standard explosives currently used. Based on a review of trinitroethyl-containing compounds available in the literature, as well as this new contribution, it is observed that high density can generally be obtained in a more targeted manner in energetic materials taking advantage of noncovalent bonding interactions, a prerequisite for the design of next generation energetic materials. [source] Peptidic modulators of protein-protein interactions: Progress and challenges in computational designBIOPOLYMERS, Issue 7 2009Mor Rubinstein Abstract With the decline in productivity of drug-development efforts, novel approaches to rational drug design are being introduced and developed. Naturally occurring and synthetic peptides are emerging as novel promising compounds that can specifically and efficiently modulate signaling pathways in vitro and in vivo. We describe sequence-based approaches that use peptides to mimic proteins in order to inhibit the interaction of the mimicked protein with its partners. We then discuss a structure-based approach, in which protein-peptide complex structures are used to rationally design and optimize peptidic inhibitors. We survey flexible peptide docking techniques and discuss current challenges and future directions in the rational design of peptidic inhibitors. © 2009 Wiley Periodicals, Inc. Biopolymers 91: 505,513, 2009. This article was originally published online as an accepted preprint. The "Published Online"date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com [source] Intracellular Uptake and Photodynamic Activity of Water-Soluble [60]- and [70]Fullerenes Incorporated in LiposomesCHEMISTRY - A EUROPEAN JOURNAL, Issue 29 2008Yuki Doi Abstract Water-soluble fullerenes have attracted attention as promising compounds that have been used to forge new paths in the field of photo-biochemistry. To prepare water-soluble fullerenes, we employed lipid-membrane-incorporated fullerenes (LMICx; x=60 or 70) by using the fullerene exchange method from a ,-cyclodextrin (,-CD) cavity to vesicles. LMIC60 have low toxicity in the dark and engender cell death by photoirradiation (,>350,nm). Furthermore, the photodynamic activity of LMIC70 is 4.7-fold that of LMIC60 for the same photon flux (,>400,nm). One of the reasons for the higher phototoxicity of LMIC70 is the higher generation of singlet oxygen (1O2) in LMIC70 than in LMIC60. The difference between LMIC60 and LMIC70 is considered to be simply derived from the amount of light absorption in the 400,700,nm region that is suitable for photodynamic therapy (PDT). To the best of our knowledge, this is the first case in which biological activity of C70 and its derivatives toward HeLa cells has been assayed. [source] Thiobarbiturates as Sirtuin Inhibitors: Virtual Screening, Free-Energy Calculations, and Biological TestingCHEMMEDCHEM, Issue 12 2008Urszula Uciechowska Abstract NAD+ -dependent histone deacetylases (sirtuins) are enzymes that cleave acetyl groups from lysine residues in histones and other proteins. Potent selective sirtuin inhibitors are interesting tools for the investigation of the biological functions of these enzymes and may be future drugs for the treatment of cancer or neurodegenerative diseases. Herein we present the results from a protein-based virtual screen of a commercial database with subsequent biological testing of the most promising compounds. The combination of docking and in,vitro experimental testing resulted in the identification of novel sirtuin inhibitors with thiobarbiturate structure. To rationalize the experimental results, free-energy calculations were carried out by molecular mechanics Poisson,Boltzmann/surface area (MM-PBSA) calculations. A significant correlation between calculated binding free energies and measured Sirt2 inhibitory activities was observed. The analyses suggested a molecular basis for the interaction of the identified thiobarbiturate derivatives with human Sirt2. Based on the docking and MM-PBSA calculations we synthesized and tested five further thiobarbiturates. The MM-PBSA method correctly predicted the activity of the novel thiobarbiturates. The identified compounds will be used to further explore the therapeutic potential of sirtuin inhibitors. [source] REVIEW: Curcumin and Alzheimer's DiseaseCNS: NEUROSCIENCE AND THERAPEUTICS, Issue 5 2010Tsuyoshi Hamaguchi Curcumin has a long history of use as a traditional remedy and food in Asia. Many studies have reported that curcumin has various beneficial properties, such as antioxidant, antiinflammatory, and antitumor. Because of the reported effects of curcumin on tumors, many clinical trials have been performed to elucidate curcumin's effects on cancers. Recent reports have suggested therapeutic potential of curcumin in the pathophysiology of Alzheimer's disease (AD). In in vitro studies, curcumin has been reported to inhibit amyloid-,-protein (A,) aggregation, and A,-induced inflammation, as well as the activities of ,-secretase and acetylcholinesterase. In in vivo studies, oral administration of curcumin has resulted in the inhibition of A, deposition, A, oligomerization, and tau phosphorylation in the brains of AD animal models, and improvements in behavioral impairment in animal models. These findings suggest that curcumin might be one of the most promising compounds for the development of AD therapies. At present, four clinical trials concerning the effects of curcumin on AD has been conducted. Two of them that were performed in China and USA have been reported no significant differences in changes in cognitive function between placebo and curcumin groups, and no results have been reported from two other clinical studies. Additional trials are necessary to determine the clinical usefulness of curcumin in the prevention and treatment of AD. [source] | ||||||||||