Showing papers in "Bioorganic & Medicinal Chemistry in 2011"

TL;DR: The flavones retusin and ayanin were found to be highly potent inhibitors of BCRP, showing only slightly less potency than Ko143, the most potent ABCG2 inhibitor known so far.

TL;DR: HyPer-2, a probe generated by a single point mutation A406V from HyPer corresponding to A233V in wtOxyR, stabilizes the dimer and expands the dynamic range of the probe.

TL;DR: A tabulated review of all marine natural product structural revisions from 2005 to 2010 is organized according to structural motif revised, finding total synthesis is a proven partner for marine, as well as terrestrial, natural products structure elucidation.

TL;DR: New arylhydrazone derivatives and a series of 1,5-diphenyl pyrazoles were designed and synthesized from 1-(4-chlorophenyl)-4,4, 4-trifuorobutane-1,3-dione and investigated in vivo for their anti-inflammatory activities and revealed a similar binding mode to SC-558, a selective COX-2 inhibitor.

TL;DR: A family of novel yet simple, amino-acid derived class I HDAC inhibitors that demonstrate isoform selectivity via access to the internal acetate release channel are reported, potentially revealing insights into the mechanism of enzymatic function through novel structural features revealed at the atomic level.

TL;DR: Evaluation of antibacterial activity showed that almost all the compounds exhibited greater activity than reference drugs and thus could be promising novel drug candidates.

TL;DR: Based on the structure-activity relationship around the naphthalene scaffold and the results of a docking study of 1a in the homology model of 17,20-lyase, the 6,7-dihydro-5H-pyrrolo[1,2-c]imidazole derivative (+)-3c was synthesized and identified as a potent and highly selective 17, 20lyase inhibitor as discussed by the authors.

TL;DR: The m- and p-bromo analogues were micromolar growth inhibitors of the LNCaP prostate cancer cell line as were the corresponding biphenyl analogues prepared from the bromide by Suzuki crosscoupling.

TL;DR: It is considered that protein knockdown with SNIPERs would be a promising alternative approach for modulating NR function and designed and synthesized degradation inducers targeting retinoic acid receptor (RAR), estrogen receptor (ER), and androgen receptor (AR).

TL;DR: The initial steps of a drug discovery effort that focused on the styryl pharmacophore combined with a ketoamide function to serve as electrophilic trap for the catalytic serine resulted in a fragment-like lead compound with reasonable target affinity and good ligand efficiency, which was extensively modified to explore structure-activity relationships.

TL;DR: Linarin prevents Aβ(25-35)-induced neurotoxicity through the activation of PI3K/Akt, which subsequently inhibits GSK-3β and up-regulates Bcl-2, raising the possibility that linarin may be a potent therapeutic compound against Alzheimer's disease acting through both acetylcholinesterase inhibition and neuroprotection.

TL;DR: This account examines recent milestone developments pertaining to compounds from invertebrates designated as therapeutic leads for biomedical discovery, focusing on the secondary metabolites, their inspirational structural scaffolds and the possible role of micro-organism associants in their biosynthesis.

TL;DR: The enzymes involved in demethylation have recently been discovered and found to be involved in cancer development and progression and a number of inhibitors have already appeared.

TL;DR: During random screening of a small in-house library of compounds, certain substituted imidazo[1,2-a]pyridines were found to be weak allosteric inhibitors of HIV-1 reverse transcriptase and showed good inhibitory activity in enzymatic (RT) and HIV anti-infectivity MAGI whole cell assays.

TL;DR: A series of new 1,3, 4-oxadiazole derivatives containing 1,4-benzodioxan moiety (6a-6s) as potential telomerase inhibitors were synthesized and showed compound 6k possessed the most potent telomersase activity.

TL;DR: This review covers the syntheses of 21 NCEs marketed in 2009 and provides insights into molecular recognition and also serves as leads for designing future new drugs.

TL;DR: A novel class of CA inhibitors, interacting with the CA isozymes I, II and IX, XII (transmembrane, tumor-associated) in a different manner, is reported here, offering the possibility to design CAIs with an interesting inhibition profile compared to the clinically used sulfonamides/sulfamates.

TL;DR: Results demonstrate that functionalization of small aromatic molecules with recognition elements can be used in the rational design of Aβ aggregation inhibitors to not only enhance inhibition but to also manipulate the inhibition mechanism.

TL;DR: The compound 59 emerged as the most potent XO inhibitor (IC(50)=5.3 μM), and some of the important interactions of 59 with the amino acid residues of active site of XO have been figured out by molecular modeling.

TL;DR: The direct anti-tubercular testing of a small compound library led to discovery of adamantyl urea hit compound 1 and the synthesis of an optimization library, noting that the compounds identified and the pharmacophore developed is consistent with inhibitors of epoxide hydrolase family of enzymes.

TL;DR: Different methods which have been developed to control cellular fluorescence activation are described, emphasizing the photochemical activation methods known to be orthogonal to most cellular components and, in addition, allowing a spatio-temporal controlled triggering of the fluorescent signal.

TL;DR: This study discovered a novel series of benzimidazole derivatives as multi-target EGFR, VEGFR-2 and PDGFR kinases inhibitors, and suggested that compound 5a more tightly interacts with EGFR andPDGFR than compound 5e.

TL;DR: The data suggest that dietary flavonoids exhibit three distinct modes of action with regard to cancer prevention, based on their hydroxyl and methoxy decoration: (1) inhibitors of CYP1 enzymatic activity, (2) CyP1 substrates and (3) substrates

TL;DR: A series of pyrazolo[1,5-a]pyrimidines were found to be novel DPP-IV inhibitors and N-[2-({2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl}amino)- 2-methylpyrazolo-6-carboxamide hydrochloride (4a) was identified.

TL;DR: This study identifies a novel class of β-glucuronidase inhibitors, benzothiazole derivatives 1-26, which are found to be the least active among the series.

TL;DR: The design and synthesis of 3-keto salicylic acid chalcone derivatives as novel HIV-1 integrase inhibitors and inhibited HIV replication with potencies comparable with their integrase inhibitory potencies are reported.

TL;DR: The 1,3,5-triazinyl-substituted benzenesulfonamides constitute thus a class of compounds with great potential for obtaining inhibitors targeting both α-class mammalian, tumor-associated, and β-class from pathogenic organisms CAs.

TL;DR: A focused library of thiolactone analogs was designed and rapidly synthesized in solution and examined the activity of the library as agonists and antagonists of LuxR-type QS receptors in Pseudomonas aeruginosa, Vibrio fischeri and Agrobacterium tumefaciens using bacterial reporter strains.

TL;DR: It is demonstrated that the newly synthesized N-mustard-quinazoline conjugates are able to induce DNA cross-linking through alkaline agarose gel shift assay and inhibited cell cycle arrest at G2/M phase.

TL;DR: The 3-aryl-2-cyanoacrylamide scaffold was designed as core pharmacophore for inhibitors of the Dengue and West Nile virus serine proteases and it turned out that the electron density of the aryl moiety and the central double bond have a crucial influence on the activity of the compounds.