Abstract:
:Combinatorial libraries continue to play a key role in drug discovery. To increase structural diversity, several experimental methods have been developed. However, limited efforts have been performed so far to quantify the diversity of the broadly used diversity-oriented synthetic libraries. Herein, we report a comprehensive characterization of 15 bis-diazacyclic combinatorial libraries obtained through libraries from libraries, which is a diversity-oriented synthetic approach. Using MACCS keys, radial and different pharmacophoric fingerprints as well as six molecular properties, it was demonstrated the increased structural and property diversity of the libraries from libraries over the individual libraries. Comparison of the libraries to existing drugs, NCI diversity, and the Molecular Libraries Small Molecule Repository revealed the structural uniqueness of the combinatorial libraries (mean similarity <0.5 for any fingerprint representation). In particular, bis-cyclic thiourea libraries were the most structurally dissimilar to drugs retaining drug-like character in property space. This study represents the first comprehensive quantification of the diversity of libraries from libraries providing a solid quantitative approach to compare and contrast the diversity of diversity-oriented synthetic libraries with existing drugs or any other compound collection.
journal_name
Chem Biol Drug Desjournal_title
Chemical biology & drug designauthors
López-Vallejo F,Nefzi A,Bender A,Owen JR,Nabney IT,Houghten RA,Medina-Franco JLdoi
10.1111/j.1747-0285.2011.01100.xsubject
Has Abstractpub_date
2011-05-01 00:00:00pages
328-42issue
5eissn
1747-0277issn
1747-0285journal_volume
77pub_type
杂志文章abstract::A variety of novel 3-butyl-2-substituted amino-3H-quinazolin-4-ones were synthesized by reacting the amino group of 3-butyl-2-hydrazino-3H-quinazolin-4-one with various aldehydes and ketones. The title compounds were investigated for analgesic, anti-inflammatory and ulcerogenic index activities. The compound 3-butyl-2...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/j.1747-0285.2007.00548.x
更新日期:2007-09-01 00:00:00
abstract::Ecdysteroids initiate the molting process in insects by binding to the ecdysone receptor (EcR), which is a promising target for identifying insect growth regulators. This paper presents an in silico/in vitro screening procedure for identifying new EcR ligands. The three-step virtual screening procedure uses a three-di...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.13772
更新日期:2021-01-01 00:00:00
abstract::Mono- and bis-indolomorphinans were synthesized through a multi-step synthetic approach from the alkaloid, thebaine, to further explore the C-ring SAR (structure-activity relationship) of morphinan scaffold. Both mono-indoles displayed good binding affinity and selectivity for the delta receptor, with compound 6b poss...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/j.1747-0285.2009.00849.x
更新日期:2009-10-01 00:00:00
abstract::GSK3β kinase is a noteworthy target for discovery of the drugs that will be used to treat several diseases. In the effort to identify a new inhibitor lead compound, we utilized thermodynamic integration (TI)-molecular dynamics (MD) simulation and kinase assay to investigate the bindings between GSK3β kinase and five c...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.12946
更新日期:2017-08-01 00:00:00
abstract::Methoxy-substituted chalcones, 3 were obtained using simple, efficient method from 2-naphtylethanone, 1 and aromatic aldehydes, 2. The in vitro cytotoxicity activities of the chalcones against a panel of three human cancer cell lines were explored. The tested compounds were found to possess significant cytotoxic activ...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.12184
更新日期:2013-12-01 00:00:00
abstract::Retrospective virtual screening experiments were carried out to investigate the effects of combining hit lists from different crystal structures of the same target using consensus scoring. An in-house High Throughput Screening (HTS) dataset from PI3K-γ was used and docked against five diverse PI3K-γ crystal structures...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/j.1747-0285.2010.01041.x
更新日期:2010-12-01 00:00:00
abstract::The first example of an inhibitor of the kinase TAK1 that binds in the DFG-out conformation is disclosed. These preliminary studies used kinase-targeted screening and structure-based drug design to create a molecule with dual pharmacological inhibition of p38 and TAK1 that demonstrated significant activity in a cell-b...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.12169
更新日期:2013-11-01 00:00:00
abstract::A series of novel 1,5-benzodiazepine derivatives were rationally designed and synthesized following the principle of the superposition of bioactive substructures by the combination of 1,5-benzodiazepine, pyridine (phenyl), and an ester group. The structures of the target compounds were determined by (1) H NMR, (13) C ...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.12739
更新日期:2016-07-01 00:00:00
abstract::Microsomal prostaglandin E synthase-1 (mPGES-1) is the key enzyme for prostaglandin E2 (PGE2) generation during inflammation and is a potential target for designing anti-inflammatory drugs. Potential inhibitors of m-PGES-1 were selected from traditional Chinese medicine (TCM Database@Taiwan) based on the pharmacophore...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/j.1747-0285.2011.01202.x
更新日期:2011-10-01 00:00:00
abstract::Anthranilic diamides is a class of insecticides target at ryanodine receptors (RyRs). To discover potent insecticides targeting at RyRs, a series of novel anthranilic diamides with a diacylhydrazine bridge were designed and synthesized. Their insecticidal activities were evaluated and a preliminary structure-activity ...
journal_title:Chemical biology & drug design
pub_type: 信件
doi:10.1111/cbdd.13349
更新日期:2018-11-01 00:00:00
abstract::We applied a novel molecular descriptor, three-dimensional biologically relevant spectrum (BRS-3D), in subtype selectivity prediction of dopamine receptor (DR) ligands. BRS-3D is a shape similarity profile calculated by superimposing the objective compounds against 300 template ligands from sc-PDB. First, we construct...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.12815
更新日期:2016-12-01 00:00:00
abstract::Three novel series of 2,5-disubstituted indole derivatives were synthesized and evaluated in vitro for their antiproliferative activity against human cancer cells and HIV-1 inhibition activity used as a readout of cellular activity. Most compounds were found to have potent anticancer activity. In particular, 2c and 3b...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.12808
更新日期:2016-11-01 00:00:00
abstract::To understand the protein transduction domain (PTD)-mediated protein transduction behavior and to explore its potential in delivering biopharmaceutic drugs, we prepared four TAT-EGFP conjugates: TAT(+)-EGFP, TAT(-)-EGFP, EGFP-TAT(+) and EGFP-TAT(-), where TAT(+) and TAT(-) represent the original and the reversed TAT s...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/j.1747-0285.2011.01315.x
更新日期:2012-05-01 00:00:00
abstract::A newly designed benzothiazolo-quinazolone series was synthesized by an aromatic amine and potassium thiocyanate in the presence of bromine in glacial acetic acid, and the final product was obtained by subsequent reaction with 5-arylamido/imidoalkyl-2-chlorobenzoic acid in the presence of potassium carbonate and furth...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/j.1747-0285.2008.00724.x
更新日期:2008-12-01 00:00:00
abstract::Transient receptor potential melastatin-2 (TRPM2) channel critical for monitoring internal body temperature is implicated in the pathological processes such as neurodegeneration. However, lacking selective and potent TRPM2 inhibitors impedes investigation and validation of the channel as a drug target. To discover nov...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.13119
更新日期:2018-02-01 00:00:00
abstract::Interstitial cystitis/painful bladder syndrome is a chronic bladder disorder with epithelial thinning or ulceration, pain, urinary frequency and urgency, for which there is no reliably effective therapy. We previously reported that interstitial cystitis/painful bladder syndrome bladder epithelial cells make a glycopep...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/j.1747-0285.2011.01108.x
更新日期:2011-06-01 00:00:00
abstract::A series of thiouracil derivatives were designed, synthesized and screened for in vitro inhibition of dipeptidyl peptidase IV. The SAR study indicated the influence of substituted chemical modifications on thiouracil scaffold. Compounds 8 (IC(50) = 0.32 μM), 9 (IC(50) = 0.29 μM), and 12 (IC(50) = 0.25 μM) showed excel...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.12070
更新日期:2013-02-01 00:00:00
abstract::The Met-enkephalin, Tyr-Gly-Gly-Phe-Met, was synthesized by the solution-phase synthesis (SPS) methodology employing -OBzl group as carboxyls' protection, while the t-Boc groups were employed for the N-terminal α-amines' protection for the majority of the amino acids of the pentapeptide sequence. The l-methionine (l-M...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.12821
更新日期:2016-12-01 00:00:00
abstract::Selective blockade of the serotonin 5-HT(2A) receptor is a useful therapeutic approach for a number of disorders, including schizophrenia, insomnia and ischaemic heart disease. A series of aporphines were docked into a homology model of the rat 5-HT(2A) receptor using AutoDock. Selected compounds with high in silico b...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.12069
更新日期:2013-02-01 00:00:00
abstract::Quantum dots (QD) are being evaluated as inorganic nanoparticles for both in vitro and in vivo optical imaging. They are also used as sensors or vehicles for targeted drug delivery combined with optical imaging. In this study, we demonstrated that glutathione-coated Ag2 S QDs (GSH-Ag2 S QDs) act as a substrate analogu...
journal_title:Chemical biology & drug design
pub_type: 信件
doi:10.1111/cbdd.13614
更新日期:2019-12-01 00:00:00
abstract::A novel series of quinolone imidazoles as new type of antimicrobial agents were synthesized. Most compounds exhibited good bioactivities especially against MRSA even superior to reference drugs. They induced bacterial resistance more slowly than clinical drugs and gave low cytotoxicity to human cells. The pKa values o...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.12532
更新日期:2015-10-01 00:00:00
abstract::Ten new xanthone derivatives have been designed and synthesized for their potential antibacterial activity. All compounds have been screened against Staphylococcus epidermidis strains ATCC 12228 and clinical K/12/8915. The highest antibacterial activity was observed for compound 3: 5-chloro-2-((4-(2-hydroxyethyl)piper...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.13803
更新日期:2020-10-08 00:00:00
abstract::Protein modification can have far-reaching effects. NEDDylation, a protein modification process with the protein NEDD8, stabilizes and modifies how the targeted protein interacts with other proteins. Its role in system regulation makes it a prime therapeutic target, and virtual high-throughput screening has already id...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.13457
更新日期:2019-04-01 00:00:00
abstract::A series of 2-pyrimidinyl-piperazinyl-alkyl derivatives of 1H-imidazo[2,1-f]purine-2,4(3H,8H)-dione has been synthesized in an attempt to discover a new class of psychotropic agents. Compounds were evaluated for their in vitro affinity for serotonin 5-HT1A , 5-HT7 , and phosphodiesterases PDE4 and PDE10. The most pote...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.13442
更新日期:2019-04-01 00:00:00
abstract::We report an advanced 'hybrid fingerprint' design concept specifically for the purpose of scaffold hopping. The generation of hybrid fingerprints includes two major steps. In the 'fingerprint reduction' step, bit positions of different types of fingerprints (e.g. substructural and pharmacophore fingerprints) are ranke...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/j.1747-0285.2009.00930.x
更新日期:2010-02-01 00:00:00
abstract::Screening combinatorial libraries of conformationally constrained peptides against macromolecular targets is utilized in identifying novel drug leads and in developing new reagents for chemical biology. In methods such as phage-display selections, biotinylated macromolecular targets are often immobilized on avidin- an...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/j.1747-0285.2006.00401.x
更新日期:2006-07-01 00:00:00
abstract::Follicle-stimulating hormone is important for mammalian reproduction. It acts through specific receptors located on the plasma membrane of granulosa cells in ovaries and Sertoli cells in testes. The binding of follicle-stimulating hormone to its receptor activates intracytoplasmic signaling pathways leading to steroid...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.12149
更新日期:2013-08-01 00:00:00
abstract::Relationships between ligand binding and the shapes of the binding sites in families of homologous enzymes are investigated by comparing matrices of distances between key binding site atoms. Multiple linear regression is used to help identify key distances that influence ligand binding affinity. In order to illustrate...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/j.1747-0285.2009.00832.x
更新日期:2009-07-01 00:00:00
abstract::Bis-indole derivatives including 1,1-bis(3'-indolyl)-1-(4-chlorophenyl)methane (DIM-C-pPhCl) and substituted quinolines such as chloroquine (CQ) and amodiaquine (AQ) are nuclear receptor 4A2 (NR4A2, Nurr1) ligands, and they exhibit anti-inflammatory activities in mouse and rat models of Parkinson's disease, respective...
journal_title:Chemical biology & drug design
pub_type: 杂志文章,评审
doi:10.1111/cbdd.13564
更新日期:2019-10-01 00:00:00
abstract::As protein/protein interactions usually trigger signalling processes, inhibitors of those interactions must preclude protein binding without eliciting the signalling process themselves. To accomplish those goals, small molecules need to target those protein residues that contribute the most to binding (binding hotspot...
journal_title:Chemical biology & drug design
pub_type: 杂志文章
doi:10.1111/cbdd.12075
更新日期:2013-01-01 00:00:00