Abstract:
AIM AND OBJECTIVE:In the last decades, cancer has become a major problem in public health all around the globe. Chimeric chemical structures have been established as an important trend on medicinal chemistry in the last years. Thiazacridines are hybrid molecules composed of a thiazolidine and acridine nucleus, both pharmacophores that act on important biological targets for cancer. By the fact it is a serious disease, seven new 3-acridin-9-ylmethyl-thiazolidine-2,4-dione derivatives were synthesized, characterized, analyzed by computer simulation and tested in tumor cells. In order to find out if the compounds have therapeutic potential. MATERIALS AND METHODS:Seven new 3-acridin-9-ylmethyl-thiazolidine-2,4-dione derivatives were synthesized through Michael addition and Knoevenagel condensation strategies. Characterization was performed by NMR and Infrared spectroscopy techniques. Regarding biological activity, thiazacridines were tested against solid and hematopoietic tumoral cell lines, namely Jurkat (acute T-cell leukemia); HL-60 (acute promyelocytic leukemia); DU 145 (prostate cancer); MOLT-4 (acute lymphoblastic leukemia); RAJI (Burkitt's lymphoma); K562 (chronic myelogenous leukemia) and normal cells PBMC (healthy volunteers). Molecular docking analysis was also performed in order to assess major targets of these new compounds. Cell cycle and clonogenic assay were also performed. RESULTS:Compound LPSF/AA-62 (9f) exhibited the most potent anticancer activity against HL-60 (IC50 3,7±1,7 μM), MOLT-4 (IC50 5,7±1,1 μM), Jurkat (IC50 18,6 μM), Du-145 (IC50 20±5 μM) and Raji (IC50 52,3±9,2 μM). While the compound LPSF/AA-57 (9b) exhibited anticancer activity against the K562 cell line (IC50 51,8±7,8 μM). Derivative LPSF/AA-62 (9f) did not interfere in the cell cycle phases of the Molt-4 lineage. However, the LPSF/AA-62 (9f) derivative significantly reduced the formation of prostate cancer cell clones. The compound LPSF/AA-62 (9f) has shown strong anchorage stability with enzymes topoisomerases 1 and 2, in particular due the presence of chlorine favored hydrogen bonds with topoisomerase 1. CONCLUSION:The 3-(acridin-9-ylmethyl)-5-((10-chloroanthracen-9-yl)methylene)thiazolidine-2,4-dione (LPSF/AA-62) presented the most promising results, showing anti-tumor activity in 5 of the 6 cell types tested, especially inhibiting the formation of colonies of prostate tumor cells (DU-145).
journal_name
Comb Chem High Throughput Screenjournal_title
Combinatorial chemistry & high throughput screeningauthors
Almeida ML,Viana DCF,da Costa VCM,Dos Santos FA,Pereira MC,Pitta MGR,de Melo Rêgo MJB,Pitta IR,Pitta MGRdoi
10.2174/1386207323666200319105239subject
Has Abstractpub_date
2020-01-01 00:00:00pages
359-368issue
5eissn
1386-2073issn
1875-5402pii
CCHTS-EPUB-105368journal_volume
23pub_type
杂志文章abstract::Over the last years microarray technology has become one of the principal platform technologies for the high-throughput analysis of biological systems. Starting with the construction of first DNA microarrays in the 1990s, microarray technology has flourished in the last years and many different new formats have been d...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章,评审
doi:10.2174/138620706777452429
更新日期:2006-06-01 00:00:00
abstract::Natural products obtained from marine sources are considered to be a rich and diverse source of potential drugs. In the present work we demonstrate the use of chemoinformatics approach for the design of new molecules inspired by molecules from marine organisms. Accordingly we have assimilated information from two majo...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207318666150703112950
更新日期:2015-01-01 00:00:00
abstract::Artificial neural networks (ANNs) have been applied for the quantitative structure-activity relationships (QSAR) studies of antibacterial activity against Escherichia coli, Serratia marcescens, Proteus vulgaris, Klebsiella pneumoniae and Pseudomonas aeruginosa of a large series of new imidazole derivatives. Antibacter...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207043328652
更新日期:2004-06-01 00:00:00
abstract:AIM AND OBJECTIVE:Lysine acetylation, as one type of post-translational modifications (PTM), plays key roles in cellular regulations and can be involved in a variety of human diseases. However, it is often high-cost and time-consuming to use traditional experimental approaches to identify the lysine acetylation sites. ...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207320666170314093216
更新日期:2017-01-01 00:00:00
abstract::Embryonic stem cells, due to their self-renewal and pluripotency properties, can be used to repair damaged tissues and as an unlimited source of differentiated cells. Although stem cells represent an important opportunity for cell based therapy and small molecules screening (in the context of drug or target discovery)...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/138620712802650540
更新日期:2012-09-01 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::Gelatinase B/MMP-9 fulfills crucial regulator or effector functions in disease states and may be pharmacologically targeted by specific inhibitors. The characteristics of cleavages of a natural gelatinase B substrate were simulated and amino acids with zinc-ion chelating side-groups were employed to design a library o...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/138620706778249758
更新日期:2006-09-01 00:00:00
abstract:BACKGROUND:Clinical outcomes after rotator cuff repair associated with diabetes mellitus(DM) are generally favorable, but no study has attempted to establish the influence of DM on outcomes after rotator cuff repair. PURPOSE:To conduct a meta-analysis of clinical studies evaluating patient outcomes between people with...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: meta分析
doi:10.2174/1386207323666201020114034
更新日期:2020-10-20 00:00:00
abstract::Sequential injection analysis (SIA) has been employed as the platform for the development of a high throughput automated assay for glutathione (GSH) in nutrition supplements. The proposed assay is based on the on-line formation of a UV-absorbing thioacrylate derivative (lambda(max) = 285 nm) upon reaction of thiol wit...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/138620710791515923
更新日期:2010-07-01 00:00:00
abstract::Unfavorable oral bioavailability is an important reason accounting for the failure of the drug candidates. Considering the lack of in vitro high-throughput screening assay for oral bioavailability, it is critical to develop in silico models for early predictions of oral bioavailability. In this review, we summarize pr...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章,评审
doi:10.2174/138620711795508368
更新日期:2011-06-01 00:00:00
abstract:BACKGROUND:In recent years, Staphylococcus aureus have developed resistance to medicines used for the treatment of human infections. Therefore, the search for antibacterial agents of high potency against Staphylococcus aureus is of great concern. Peptide deformylase (PDF), a metalloprotease catalyzing the removal of a ...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207321666180220124259
更新日期:2018-01-01 00:00:00
abstract::Most essential functions are associated with various protein-protein interactions, particularly the cytokine-receptor interaction. Knowledge of the heterogeneous network of cytokine- receptor interactions provides insights into various human physiological functions. However, only a few studies are focused on the compu...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207319666151110122621
更新日期:2016-01-01 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::A pulsed ultrafiltration-mass spectrometric screening method has been developed to evaluate the metabolic stability of drugs. Pooled human liver microsomes containing cytochrome P450 enzymes were trapped by an ultrafiltration membrane in a stirred flow-through chamber, and eight beta-blocker drugs including acebutolol...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207023330633
更新日期:2002-02-01 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: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:OBJECTIVE:Osteopontin (OPN), a phosphorylated sialoprotein, has been shown to overexpress in a variety of cancers and to contribute tumor progression and metastasis by increasing cell migration and adhesion. In the current study, we aimed to investigate the prognostic and predictive role of OPN in patients with advance...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207323666200902135349
更新日期:2020-09-02 00:00:00
abstract::Approximately 5-10% of all colorectal carcinomas arise from cancer predisposition syndromes caused by heterozygote germline mutations in post-replicative DNA mismatch repair (MMR) genes. In contrast to gastrointestinal polyposis syndromes, carcinomas in these patients do not occur on the background of increased number...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207003331409
更新日期:2000-12-01 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::Combinatorial phage peptide libraries have been used to identify the ligands for specific target molecules. These libraries are also useful for identification of the specific substrates of various proteases. A substrate phage library has a random peptide sequence at the N-terminus of the phage coat protein and an addi...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207013330788
更新日期:2001-11-01 00:00:00
abstract::Development of calcium channel blockers is attractive, but has in the past been hampered by lack of high throughput electrophysiological technology. This limitation has been overcome by the implementation of automated patch clamp systems that allow identification of state-dependent compounds, which preferentially targ...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207311316030008
更新日期:2013-03-01 00:00:00
abstract:BACKGROUND:Topological indices have numerous implementations in chemistry, biology and in lot of other areas. It is a real number associated to a graph, which provides information about its physical and chemical properties and their correlations. For a connected graph H, the degree distance defined as DD(H)=∑_(\{h_1,h_...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207323666201224123643
更新日期:2020-12-24 00:00:00
abstract::The identification of clones expressing high levels of recombinant protein in Pichia pastoris is usually dependant upon SDS-PAGE, Western blotting, or bioactivity-based assays that are labour and time-consuming. We describe a rapid method that images green fluorescence protein (GFP) of individual P. pastoris clones tr...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/138620710791292967
更新日期:2010-06-01 00:00:00
abstract::Survival of cells and maintenance of genome depend on detection and repair of damaged DNA through intricate mechanisms. Cancer treatment relies on chemotherapy or radiation therapy that kills neoplastic cells by causing immense damage to the DNA. In many cases, escalated DNA repair mechanism leads to resistance agains...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207318666150626093648
更新日期:2015-01-01 00:00:00
abstract::The appropriate selection of initial receptor structure has been the 'cornerstone' or foundation of successful structure-based virtual screening (SBVS), and plagued the structure-based design with a significantly practical problem to determine the major physiological states or important transition states of receptors ...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207323666201110150140
更新日期:2020-11-10 00:00:00
abstract::The recent success of the human genome project and the continued accomplishment in obtaining DNA sequences for a vast array of organisms is providing an unprecedented wealth of information. Nevertheless, an abundance of the proteome contains hypothetical proteins or proteins of unknown function, where high throughput ...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章,评审
doi:10.2174/138620707782507331
更新日期:2007-09-01 00:00:00
abstract::The aim of this study was to examine the anticancer activities and phytochemical profiles of Dicranum scoparium against HeLa cell lines. The bio-guided fractionation studies of dichloromethane extract have high antiproliferative activities. Fractions 7, 9, 19, 20 are rich source of unsaturated fatty acids, and- in the...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207318666150305112504
更新日期:2015-01-01 00:00:00
abstract::For years, the physicochemical properties of drug candidates have been used to predict their in vivo pharmacokinetic behaviors. Several theories and empirical correlations have been established by various researchers with the overall goal of expediting the drug candidate selection process, with greater confidence and ...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/138620709787581693
更新日期:2009-03-01 00:00:00
abstract:BACKGROUND:Lead (Pb) remains a common contaminant in the environment in many parts of the world. Pb exposure adversely affects many human organs, including the gonads, via oxidant and inflammatory marker propagation in affected tissues. Moringa oleifera leaf extract (MOE) is a rich source of antioxidants reported to ha...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207323666200923142831
更新日期:2020-09-23 00:00:00
abstract::A three-component 3+2 cycloaddition reaction followed by Suzuki coupling reaction was carried out to synthesize a library of compounds using automation (parallel synthesizer). Scaffolds that are unexplored in literature were used for the synthesis of library. The iodo-triazoles formed by 3+2 cycloaddition reaction wer...
journal_title:Combinatorial chemistry & high throughput screening
pub_type: 杂志文章
doi:10.2174/1386207311316080009
更新日期:2013-09-01 00:00:00