Abstract:
:The problem of predicting torsadogenic cardiotoxicity of drugs is afforded in this work. QSAR studies on a series of molecules, acting as hERG K+ channel blockers, were carried out for this purpose by using the CODESSA program. Molecules belonging to the analyzed dataset are characterized by different therapeutic targets and by high molecular diversity. The predictive power of the obtained models was estimated by means of rigorous validation criteria implying the use of highly diagnostic statistical parameters on the test set, other than the training set. Validation results obtained for a blind set, disjoined from the whole dataset initially considered, confirmed the predictive potency of the models proposed here, so suggesting that they are worth to be considered as a valuable tool for practical applications in predicting the blockade of hERG K+ channels.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Coi A,Massarelli I,Murgia L,Saraceno M,Calderone V,Bianucci AMdoi
10.1016/j.bmc.2005.12.030subject
Has Abstractpub_date
2006-05-01 00:00:00pages
3153-9issue
9eissn
0968-0896issn
1464-3391pii
S0968-0896(05)01212-5journal_volume
14pub_type
杂志文章abstract::We designed, synthesized and evaluated 13 novel tricyclic indeno[2,1-d]pyrimidines as RTK inhibitors. These analogues were synthesized via a Dieckmann condensation of 1,2-phenylenediacetonitrile followed by cyclocondensation with guanidine carbonate to afford the 2-amino-3,9-dihydro-indeno[2,1-d]pyrimidin-4-one. Sulfo...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2012.05.068
更新日期:2012-07-15 00:00:00
abstract::Human lipoxygenases (hLO) have been implicated in a variety of diseases and cancers and each hLO isozyme appears to have distinct roles in cellular biology. This fact emphasizes the need for discovering selective hLO inhibitors for both understanding the role of specific lipoxygenases in the cell and developing pharma...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2007.08.015
更新日期:2007-11-15 00:00:00
abstract::Screening of a library of diverse heterocyclic scaffolds identified substituted quinolines as inhibitors of the human proteasome. The heterocyclic library was prepared via a novel titanium-catalyzed multicomponent coupling reaction, which rendered a diverse set of isoxazoles, pyrimidines, pyrroles, pyrazoles and quino...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2016.04.005
更新日期:2016-06-01 00:00:00
abstract::NAD(P)H:quinone reductase 1 (QR1) belongs to a class of enzymes called cytoprotective enzymes. It exhibits its cancer protective activity mainly by inhibiting the formation of intracellular semiquinone radicals, and by generating α-tocopherolhydroquinone, which acts as a free radical scavenger. It is therefore believe...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2012.10.006
更新日期:2012-12-15 00:00:00
abstract::Novel chemical entities were prepared via Suzuki and S(N) reaction as AC-ring substrate mimetics of CYP17. The synthesised compounds 1-31 were tested for activity using human CYP17 expressed in Escherichia coli. Promising compounds were tested for selectivity against hepatic CYP enzymes (3A4, 2D6, 1A2, 2C9, 2C19, 2B6)...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2007.10.094
更新日期:2008-02-15 00:00:00
abstract::Small molecules are central players in chemical biology studies. They promote the perturbation of cellular processes underlying diseases and enable the identification of biological targets that can be validated for therapeutic intervention. Small molecules have been shown to accurately tune a single function of plurip...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章,评审
doi:10.1016/j.bmc.2014.04.019
更新日期:2014-08-15 00:00:00
abstract::We describe a new route for the synthesis of (S)-N-Boc-5-oxaproline. This building block is a key element for the chemical synthesis of proteins with the α-ketoacid-hydroxylamine (KAHA) ligation. The new synthetic pathway to the enantiopure oxaproline is based on a chiral amine mediated enantioselective conjugate addi...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2017.06.019
更新日期:2017-09-15 00:00:00
abstract::New series of 3-phenylquinoxaline 1,4-di-N-oxide with selective activity against Mycobacterium tuberculosis have been prepared and evaluated. Thirty-four of the seventy tested compounds showed an MIC value less than 0.2 microg/mL, a value on the order of the MIC of rifampicin. Furthermore, 45% of the evaluated derivat...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2008.10.086
更新日期:2009-01-01 00:00:00
abstract::The proteasome, a validated cellular target for cancer, is central for maintaining cellular homeostasis, while fatty acid synthase (FAS), a novel target for numerous cancers, is responsible for palmitic acid biosynthesis. Perturbation of either enzymatic machine results in decreased proliferation and ultimately cellul...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2017.01.020
更新日期:2017-06-01 00:00:00
abstract::The multi-step ligand action to a target protein is an important aspect when understanding mechanisms of ligand binding and discovering new drugs. However, structurally capturing such complex mechanisms is challenging. This is particularly true for interactions between large membrane proteins and small molecules. One ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2018.10.012
更新日期:2018-11-15 00:00:00
abstract::Aromatic alpha-amino-alpha-methyl acids and alpha-hydrazino-alpha-methyl acids are known aromatic amino acid decarboxylase inhibitors. Specific derivatives such as 2-amino-2-methyl-3-(3,4- dihydroxyphenyl)propanoate, Aldomet, and 2-hydrazino-2-methyl-3-(3,4- dihydroxyphenyl)propanoate, Lodosyn, have been developed as ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/0968-0896(94)85002-x
更新日期:1994-07-01 00:00:00
abstract::Breast cancer resistance protein (BCRP/ABCG2) belongs to the ATP binding cassette family of transport proteins. BCRP has been found to confer multidrug resistance in cancer cells. A strategy to overcome resistance due to BCRP overexpression is the investigation of potent and specific BCRP inhibitors. The aim of the cu...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2011.10.074
更新日期:2012-01-01 00:00:00
abstract::The expression and function of endothelin (ET) receptors is abnormal in cardiovascular diseases, tumor progression, and tumor metastasis. In this study, we prepared two [(18)F]-fluorinated derivatives of the non-peptide ET(A) receptor antagonist PD 156707 and evaluated their ET receptor binding potencies. Ex vivo as w...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2009.08.058
更新日期:2009-10-15 00:00:00
abstract::Two zinc(II) phthalocyanines bearing either four methoxy (ZnPc 3) or trifluoromethylbenzyloxy (ZnPc 4) substituents have been synthesized by a two-step procedure starting from 4-nitrophthalonitrile. Absorption and fluorescence spectroscopic studies were analyzed in different media. These compounds are essentially non-...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2004.10.003
更新日期:2005-01-03 00:00:00
abstract::A combination of fluorophore and nucleobase through a π-conjugated rigid linker integrates the base pairing and the fluorescence change into a single event. Such base discriminating fluorophore can change its fluorescence as a direct response to the base pairing event and therefore have advantages over tethered labels...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2017.10.008
更新日期:2017-12-15 00:00:00
abstract::The effect of 7,8-diacetoxy-4-methylcoumarin (DAMC) has been studied on hepatic NADPH cytochrome C reductase-- an enzyme participating in the microsomal electron transport. The preincubation of liver microsomes with DAMC resulted in a time-dependent activation of NADPH cytochrome C reductase. The catalytic activity of...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(98)00228-4
更新日期:1999-02-01 00:00:00
abstract::A library of chalcones with basic functionalities were screened for inhibition of P-glycoprotein (Pgp, ABCB1) by the calcein-AM accumulation assay on MDCKII/MDR1 cells. Three members that had ring A substituted with 5-(1-ethylpiperidin-4-yl) and 2,4-dimethoxy groups were found to increase calcein-AM accumulation to a ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2007.10.006
更新日期:2008-01-01 00:00:00
abstract::MGAT2 (monoacylglycerol acyltransferase 2) is expected to be an attractive target for the drug treatment of obesity, diabetes, and other disease. We describe our exploration and structure-activity relationship (SAR) study of 2,3-dihydro-1H-isoindole-5-sulfonamide derivatives. In this study, we identified 29 as an oral...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2015.06.065
更新日期:2015-09-01 00:00:00
abstract::Parviflorene F (1), a novel sesquiterpenoid dimer isolated from Curcuma parviflora Wall, is a cytotoxic compound. In this study, we examined the mechanism of its cytotoxic effect in HeLa cells. Treatment with 1 enhanced the mRNA and protein expression of TRAIL-R2 (tumor necrosis factor alpha-related apoptosis inducing...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2007.11.022
更新日期:2008-02-15 00:00:00
abstract::The present study describes the chemical synthesis and pharmacological evaluation of a new series of eleven compounds stereoisomers of imidobenzenesulfonylaziridines in the forced-swimming test (FST) in mice. The pharmacological results of these compounds show that six of them, given intraperitoneally, reduced the imm...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2006.03.036
更新日期:2006-08-01 00:00:00
abstract::Three new derivatives of 2-substituted 1,3,4-thiadiazole-5-sulfonamide have been synthesized. These compounds are 2-(3-chloropropionylamino)-1,3,4-thiadiazole-5-sulfonamide (1); 2-(2,2-dichloroacetylamino)-1,3,4-thiadiazole-5-sulfonamide (2); and 2-(3-phenylpropionylamino)-1,3,4-thiadiazole-5-sulfonamide (3). Inhibiti...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(96)00272-6
更新日期:1997-03-01 00:00:00
abstract::Synthetic 6-chromanol derivatives were prepared with several chlorine substitutions, which conferred both electron-withdrawing inductive effects and electron-donating resonance effects. A trichlorinated compound (2), a dichlorinated compound (3), and three monochlorinated compounds (4, 5, and 6) were synthesized; comp...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2012.05.008
更新日期:2012-07-01 00:00:00
abstract::Protein citrullination is just one of more than 200 known PTMs. This modification, catalyzed by the protein arginine deiminases (PADs 1-4 and PAD6 in humans), converts the positively charged guanidinium group of an arginine residue into a neutral ureido-group. Given the strong links between dysregulated PAD activity a...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2013.12.064
更新日期:2014-02-15 00:00:00
abstract::(R)-1-(10,11-Dihydro-dibenzo[b,f]azepin-5-yl)-3-methylamino-propan-2-ol ((R)-OHDMI) and (S,S)-1-cyclopentyl-2-(5-fluoro-2-methoxy-phenyl)-1-morpholin-2-yl-ethanol (CFMME) were synthesized and found to be potent inhibitors of norepinephrine reuptake. Each was labelled efficiently in its methyl group with carbon-11 (t(1...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2006.10.065
更新日期:2007-01-15 00:00:00
abstract::Inhibition of acetylcholinesterase (AChE) and therefore prevention of acetylcholine degradation is one of the most accepted therapy opportunities for Alzheimer s disease (AD), today. Due to lack of selectivity of AChE inhibitor drugs on the market, AD-patients suffer from side effects like nausea or vomiting. In the p...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2010.01.074
更新日期:2010-03-15 00:00:00
abstract::Anthraquinone-based compounds are attractive target for the design of new anticancer drugs. We have previously described a series of 1,5- and 1,4-difunctionalized anthraquinones, which exhibit different spectra of potency, together with human telomerase evaluation. The present study details the preparation of further,...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2004.09.001
更新日期:2004-12-01 00:00:00
abstract::Novel Probenecid-based amide derivatives, incorporating different natural amino acids, were synthesized and assayed to test their effect on the human carbonic anhydrase (hCA, EC 4.2.1.1) transmembrane isoforms hCA IX and XII over the ubiquitous isoforms hCA I and II. Most of them presented a complete loss of hCA II in...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2015.07.066
更新日期:2015-09-01 00:00:00
abstract::Thymidylate synthase (TS) (EC 2.1.1.45), an enzyme involved in the DNA synthesis of both prokaryotic and eukaryotic cells, is a potential target for the development of anticancer and antinfective agents. Recently, we described a series of phthalein and naphthalein derivatives as TS inhibitors. These compounds have str...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(02)00541-2
更新日期:2003-03-20 00:00:00
abstract::The synthesis of N-[7-(2-amino-3,4-dihydro-4-oxo-quinazolin-6-yl) -6-formyl-1-oxo-heptyl]-L-glutamic acid (2, abenzyl 10-formyl-5,8,10-trideazafolic acid) as a potential enzyme-assembled tight binding inhibitor of glycinamide ribonucleotide transformylase (GAR Tfase) or aminoimidazole carboxamide ribonucleotide transf...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(97)00123-5
更新日期:1997-09-01 00:00:00
abstract::For the purpose of rational modification of the TRH molecule, we were pursuing an approach that consists of two steps: (1) 'obligatory' replacement of histidine with glutamine in TRH and (2) the application of conformational constraints for putative bioactive conformation I stabilized by an intramolecular hydrogen bon...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(97)00141-7
更新日期:1997-11-01 00:00:00