Abstract:
:Polo-like kinase 1 (Plk1) is a decisive enzyme with its multifunctional activity in cell cycle progression especially mitosis. The over expression of Plk1 in broad spectrum of cancer types turns into a promising therapeutic target against cancer. In the present study, several ligand based pharmacophore models and atom based 3D-QSAR models have been generated using a series of 49 thiazole and thiophene derivatives with well prescribed Plk1 inhibitory activity. From the generated models, the AADRR hypothesis associated with an atom based 3D-QSAR model provided a satisfactory statistical significance containing predictive ability of 40 training set (R(2) = 0.9539, SD = 0.1789, F = 113.8) and nine test set (Q(2) = 0.4868, RMSE = 0.5333, Pearson R = 0.7114) molecules. The Hypothesis, AADRR explains the salient structural features of the molecules and the developed 3D-QSAR model points out the effect of hydrophobic groups, electron withdrawing groups and H-bond donor groups on Plk1 inhibition for the most active compound 47. The results were further supported by molecular docking studies, which explain the hydrogen bond interactions and binding mode of the ligands with Plk1. These molecular modelling results are expected to be useful for further design of active Plk1 inhibitors.
journal_name
Comb Chem High Throughput Screenjournal_title
Combinatorial chemistry & high throughput screeningauthors
Chekkara R,Gorla VR,Susithra E,Tenkayala SRdoi
10.2174/1386207317666141024152910subject
Has Abstractpub_date
2014-01-01 00:00:00pages
848-58issue
10eissn
1386-2073issn
1875-5402pii
CCHTS-EPUB-63041journal_volume
17pub_type
杂志文章abstract::This review describes computational procedures for deriving the amino acid sequences that are compatible with a given protein backbone structure. Such procedures can be used to gain insight into the constraints imposed by the 3D structure of the protein sequence, or to design proteins that are likely to adopt a given ...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章,评审
doi:10.2174/1386207013330724
更新日期:2001-12-01 00:00:00
abstract::A new multicomponent domino reaction for rapid and regioselective synthesis of highly functionalized benzo[h]naphtho[2,3-a]acridine-15,16(5H,14H)-diones has been established. The reaction can be conducted by using readily available and inexpensive substrates under microwave irradiation. The procedures are facile, avoi...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/138620712800194459
更新日期:2012-06-01 00:00:00
abstract::Accurate classification of instances depends on identification and removal of redundant features. Classification of data having high dimensionality is usually performed in conjunction with an appropriate feature selection method. Feature selection enables identification of the most informative feature subset from the ...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/138620709788488993
更新日期:2009-06-01 00:00:00
abstract:AIM AND OBJECTIVE:This study was designed to explore the active compounds and significant pathways of Guizhi-Shaoyao-Zhimu decoction (GSZD) for treating diabetes mellitus using molecular docking combined with network pharmacology. MATERIALS AND METHODS:Chemical constituents of GSZD and diabetes-related target proteins...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207322666191022101613
更新日期:2019-01-01 00:00:00
abstract::As technologies for high throughput and high content screening continue to evolve, new platforms for quantitative cellular imaging will play an increasingly important role in identifying and profiling lead compounds. To gain insight into the effects of a compound on cell morphology or intracellular events, it is neces...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章,评审
doi:10.2174/138620709789383204
更新日期:2009-11-01 00:00:00
abstract::In recent years, combinatorial libraries have become a major tool for drug discovery and drug development. Along the way, one potential use of combinatorial chemistry libraries almost been neglected: the basic study of intermolecular interactions. Especially "one-bead-one-structure" libraries can be a powerful means f...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章,评审
doi:
更新日期:1998-10-01 00:00:00
abstract::High Throughput experimentation has been well established as a tool in early stage catalyst development and catalyst and process scale-up today. One of the more challenging areas of catalytic research is polymer catalysis. The main difference with most non-polymer catalytic conversions is the fact that the product is ...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/138620712798868374
更新日期:2012-02-01 00:00:00
abstract:OBJECTIVE:Lung cancer is the most prevalent cancer in the world, and lung adenocarcinoma is the most common lung cancer subtype. Identification and determination of relevant prognostic markers are the key steps to personalized cancer management. METHODS:We collected the gene expression profiles from 265 tumor tissues ...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207322666190404152140
更新日期:2019-01-01 00:00:00
abstract::The Molecular Screening Shared Resource (MSSR) offers a comprehensive range of leading-edge high throughput screening (HTS) services including drug discovery, chemical and functional genomics, and novel methods for nano and environmental toxicology. The MSSR is an open access environment with investigators from UCLA a...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207317666140323134621
更新日期:2014-05-01 00:00:00
abstract::African trypanosomes are extracellular blood parasites that cause sleeping sickness in humans and Nagana in cattle. The therapeutics used to control and treat these diseases are very ineffective and thus, the development of new drugs is urgently needed. We have previously suggested to use trypanosome-specific RNA apta...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/138620706777935324
更新日期:2006-08-01 00:00:00
abstract::A pulsed ultrafiltration-mass spectrometric screening assay has been developed to generate and identify electrophilic metabolites of xenobiotic compounds formed by hepatic cytochrome P450 enzymes. This assay would be suitable for the early identification of potentially toxic compounds during the initial phase of drug ...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:
更新日期:1999-06-01 00:00:00
abstract::Single nucleotide polymorphisms (SNPs) are the most abundant variations in the human genome and have become the primary markers for genetic studies for mapping and identifying susceptible genes for complex diseases. Methods that genotype SNPs quickly and economically are of high values for these studies because they r...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章,评审
doi:10.2174/138620703106298392
更新日期:2003-05-01 00:00:00
abstract::Voltage-clamp techniques are typically used to study the plasma membrane proteins, such as ion channels and transporters that control bioelectrical signals. Many of these proteins have been cloned and can now be studied as potential targets for drug development. The two approaches most commonly used for heterologous e...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章,评审
doi:10.2174/138620709787047975
更新日期:2009-01-01 00:00:00
abstract::Building accurate quantitative structure-activity relationships (QSAR) is important in drug design, environmental modeling, toxicology, and chemical property prediction. QSAR methods can be utilized to solve mainly two types of problems viz., pattern recognition, (or classification) where output is discrete (i.e. clas...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章,评审
doi:10.2174/138620709788167908
更新日期:2009-05-01 00:00:00
abstract::This paper aims to review recent developments in the synthesis of quinazolines and quinazolinone derivatives under conditions that include the application of microwave heating in the ring forming step. Recently, two reviews on the synthesis and chemistry of natural and synthetic quinazolines and quinazolinones have be...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章,评审
doi:10.2174/138620707783220356
更新日期:2007-12-01 00:00:00
abstract:BACKGROUND:Depression is a mental illness caused by the imbalance of important neurotransmitters such as serotonin (5-HT) and norepinephrine (NE). It is a serious neurological disorder that could be treated by antidepressant drugs. OBJECTIVE:There are two major classes such as TCAs and phenoxyphenylpropylamines which ...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207323666200901104222
更新日期:2020-08-31 00:00:00
abstract::High throughput screening (HTS) campaigns, where laboratory automation is used to expose biological targets to large numbers of materials from corporate compound collections, have become commonplace within the lead generation phase of pharmaceutical discovery. Advances in genomics and related fields have afforded a we...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/138620706775541891
更新日期:2006-02-01 00:00:00
abstract:AIM AND OBJECTIVE:The rapid increase in the amount of protein sequence data available leads to an urgent need for novel computational algorithms to analyze and compare these sequences. This study is undertaken to develop an efficient computational approach for timely encoding protein sequences and extracting the hidden...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207321666180130100838
更新日期:2018-01-01 00:00:00
abstract:AIM AND OBJECTIVE:Lung cancer is a highly heterogeneous cancer, due to the significant differences in molecular levels, resulting in different clinical manifestations of lung cancer patients there is a big difference. Including disease characterization, drug response, the risk of recurrence, survival, etc. Method:Clin...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207322666190125151624
更新日期:2018-01-01 00:00:00
abstract:AIM AND OBJECTIVE:Flap endonuclease-1 (FEN1) plays a central role in DNA replication and DNA damage repair process. In mammals, FEN1 functional sites variation is related to cancer and chronic inflammation, and supports the role of FEN1 as a tumor suppressor. However, FEN1 is overexpressed in multiple types of cancer c...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207322666190704095602
更新日期:2019-01-01 00:00:00
abstract::Therapeutic options for many infections are extremely limited and at crisis point. We run the risk of entering a second pre-antibiotic era. There had been no miracle drug for the patients infected by resistant microbial pathogens. Most of the very few new drugs under development have problems with their toxicity, or p...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章,评审
doi:10.2174/13862073113166660065
更新日期:2014-01-01 00:00:00
abstract::An efficient, one-pot and three-component synthesis of biologically important heterocyclic compounds is described from the reaction of primary amines and phenyl isothiocyanate in the presence of acryloyl chloride at room temperature without the need to use any catalyst. ...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207317666140313110334
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:The breast is an important biological system of human with two distinct states, i.e. normal and tumoral. Research on breast cancer could be based on systematic modeling to contrast the system structures of these two states. OBJECTIVE:We use mutual information for the construction of the gene network of brea...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207319666160831152801
更新日期:2016-01-01 00:00:00
abstract::In this review various technologies and approaches for the utilization of mass spectrometry in high-throughput analyses are discussed. The use of quadrupole-based mass spectrometry in the screening of chemical libraries against enzymatic targets for the identification of inhibitors and/or activators is highlighted. Th...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章,评审
doi:10.2174/138620709789104924
更新日期:2009-09-01 00:00:00
abstract::As HTS technologies come of age, pharmaceutical companies are focusing increasingly on the quality of their screening collections. Storage conditions and their influence on compound stability and solubility are debated intensely. At Novartis, a strategy was developed that is different to most other companies: (1) comp...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207054867328
更新日期:2005-09-01 00:00:00
abstract::Microwave-assisted Suzuki-Miyaura and Stille cross-coupling reactions for the synthesis of highly electron-rich and diversely functionalized biaryl intermediates are presented. Microwave-irradiation has been demonstrated to be a very powerful tool for performing difficult transition metal-catalyzed cross-coupling reac...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/138620707783018513
更新日期:2007-11-01 00:00:00
abstract::P-glycoprotein (P-gp) is well known to cause multidrug resistance (MDR) in cancer cells. This MDR leads to cancer recurrence which is a major obstacle in cancer treatment. High P-gp expression has been observed in the population of cancer stem cells (CSCs) having self-renewal potential. Early detection and inhibition ...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 历史文章,杂志文章
doi:10.2174/1386207319666160517115158
更新日期:2016-01-01 00:00:00
abstract::Substructural Molecular Fragments (SMF) method was applied for computer-aided design of new compounds potentially possessing high anti-HIV activities: tetrahydroimidazobenzodiazepinone (TIBO) derivatives and 1-[2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) derivatives. Using available experimental data, the SMF...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207054546513
更新日期:2005-08-01 00:00:00
abstract::NMR has proven to be a valuable tool for identifying small molecule drug leads that serve as starting points for lead optimization programs. In addition, NMR screening can also be applied during lead optimization in order to improve the pharmacokinetic properties of a compound. In this paper we review the NMR methods ...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章,评审
doi:10.2174/1386207023329941
更新日期:2002-12-01 00:00:00
abstract::A new and simple high-performance liquid chromatography method was developed and validated for the simultaneous determination of retinol, retinyl palmitate, β-carotene, α-tocopherol and vitamin C in rat serum treated with Plantago Major L. and 7,12 dimethylbenz[a]anthracene. High-performance liquid chromatography anal...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:
更新日期:2013-02-01 00:00:00