Abstract:
:A novel series of 2-pyrazoline derivatives were designed, synthesized, and evaluated for cholinesterase (ChE) inhibitory, Aβ anti-aggregating and neuroprotective activities. Among these, 3d, 3e, 3g, and 3h were established as the most potent and selective BChE inhibitors (IC50 = 0.5-3.9 μM), while 3f presented dual inhibitory activity against BChE and AChE (IC50 = 6.0 and 6.5 μM, respectively). Kinetic analyses revealed that 3g is a partial noncompetitive inhibitor of BChE (Ki = 2.22 μM), while 3f exerts competitive inhibition on AChE (Ki = 0.63 μM). The active compounds were subsequently screened for further assessments. 3f, 3g and 3h reduced Aβ1-42 aggregation levels significantly (72.6, 83.4 and 63.4%, respectively). In addition, 3f demonstrated outstanding neuroprotective effects against Aβ1-42-induced and H2O2-induced cell toxicity (95.6 and 93.6%, respectively). Molecular docking studies were performed with 3g and 3f to investigate binding interactions inside the active sites of BChE and AChE. Compounds 3g and 3f might have the multifunctional potential for use against Alzheimer's disease.
journal_name
Medchemcommjournal_title
MedChemCommauthors
Unsal-Tan O,Tüylü Küçükkılınç T,Ayazgök B,Balkan A,Ozadali-Sari Kdoi
10.1039/c9md00030esubject
Has Abstractpub_date
2019-05-09 00:00:00pages
1018-1026issue
6eissn
2040-2503issn
2040-2511pii
c9md00030ejournal_volume
10pub_type
杂志文章相关文献
MedChemComm文献大全abstract::As the protein databank (PDB) recently passed the cap of 123 456 structures, it stands more than ever as an important resource not only to analyze structural features of specific biological systems, but also to study the prevalence of structural patterns observed in a large body of unrelated structures, that may refle...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c7md00381a
更新日期:2017-10-01 00:00:00
abstract::The cytotoxic drug gemcitabine (GEM) has been conjugated to receptor-binding peptides to target melanoma tumors. A hexapeptide having a Lys-Gly-His-Lys sequence (pep-1), an octapeptide with an Arg-Gly-Asp-Lys-Gly-His-Lys sequence (pep-2), a GEM-conjugated Lys-Gly-His-Lys peptide (GEM-pep-3) and a GEM-conjugated Asp-Gl...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c7md00638a
更新日期:2018-03-06 00:00:00
abstract::In this review, we have focused on the recent progress in metal complexes that are able to bind to β-amyloid (Aβ) species. We have discussed various radioactive complexes of 99mTc, 68Ga, 64Cu, 89Zr, and 111In, which were designed as Aβ imaging agents for positron emission tomography (PET) and single photon emission co...
journal_title:MedChemComm
pub_type: 杂志文章,评审
doi:10.1039/c7md00064b
更新日期:2017-05-16 00:00:00
abstract::Novel primaquine-cell penetrating peptide conjugates were synthesised and tested in vitro against liver stage Plasmodium berghei parasites. Generally, the conjugates were more active than the parent peptides and, in some cases, than the parent drug. These are unprecedented findings that may open a new route towards an...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c8md00447a
更新日期:2018-11-16 00:00:00
abstract::[This corrects the article DOI: 10.1039/C7MD00637C.]. ...
journal_title:MedChemComm
pub_type: 杂志文章,已发布勘误
doi:10.1039/c8md90009d
更新日期:2018-03-02 00:00:00
abstract::Two diazabicyclo analogues of maraviroc, in which the azabicyclooctane moiety is replaced by diazabicyclooctane or diazabicyclononane, were synthesized and tested, through a viral neutralization assay, on a panel of six pseudoviruses. The diazabicyclooctane derivative maintained a significant infectivity reduction pow...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c6md00575f
更新日期:2016-12-16 00:00:00
abstract::The introduction of proteins into dendritic cells (DCs) ex vivo is a critical step for the DC-based immunotherapy of cancer. Here, we developed a biotin-modified polymer with multiple hydrophobic membrane anchors for cells that functions as a synthetic receptor for an antigen protein, ovalbumin (OVA), to introduce it ...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c7md00188f
更新日期:2017-05-12 00:00:00
abstract::Twenty-three monoketone derivatives of curcumin were synthesized to investigate the synergy with fluconazole against fluconazole-resistant Candida spp. The minimal inhibitory concentration (MIC80) and the fractional inhibitory concentration index (FICI) of the antifungal synergist fluconazole were measured against flu...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c6md00649c
更新日期:2017-03-17 00:00:00
abstract::A novel and simplified synthetic scaffold based on pladienolide was designed using a consensus pharmacophore hypothesis. An initial target was synthesized and evaluated to examine the role of the 3-hydroxy group and the methyl groups present at positions 10, 16, 20, 22 in 1, on biological activity. We report the first...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/C1MD00040C
更新日期:2011-01-01 00:00:00
abstract::The potential for carbon monoxide-releasing molecules (CO-RMs) as antimicrobials represents an exciting prospective in the fight against antibiotic resistance. Trypto-CORM, a tryptophan-containing manganese(i) carbonyl, is toxic against E. coli following photo-activation. Here, we demonstrate that Trypto-CORM is toxic...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c6md00603e
更新日期:2016-12-06 00:00:00
abstract::A series of 18 new 5-[3-(4-aryl-1-piperazinyl)propoxy]coumarin derivatives from the corresponding bromoalkyl derivatives have been designed and synthesized by us using a microwave-assisted protocol. Radioligand binding assays of this series of compounds as well as a previously synthesized series of 17 structurally-sim...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c7md00281e
更新日期:2017-07-03 00:00:00
abstract::A series of indole derivatives was designed and synthesised to improve on activity and circumvent pharmacokinetic limitations experienced with the structurally related compound, ladostigil. The compounds consisted of a propargylamine moiety (a known MAO inhibitor and neuroprotector) at the N1 position and a ChE inhibi...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c7md00569e
更新日期:2018-01-16 00:00:00
abstract::The synthesis, biological evaluation and molecular modeling of a series of pyrrole compounds related to 3,5-dibromo-4-(3,4-dimethoxyphenyl)-1H-pyrrole-2-carboxylic acid that evaluates and optimizes C-4 substituents are reported. The key factor for microtubule depolymerization activity appears to be the presence of an ...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/C2MD20320K
更新日期:2013-01-01 00:00:00
abstract::Covalent probes and drugs have found widespread use as research tools and clinical agents. Covalent probes are useful because of their increased intracellular potency and because covalent labeling of cellular proteins can be tracked using click chemistry. Covalent drugs, on the other hand, can overcome drug resistance...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c5md00518c
更新日期:2016-04-01 00:00:00
abstract::New derivatives of aminoglycosides containing 6'-carboxylic acid or 6'-amide on their ring I were designed, synthesized and their ability to readthrough nonsense mutations was examined in vitro, along with the protein translation inhibition in prokaryotic and eukaryotic systems. The observed structure-activity relatio...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c8md00001h
更新日期:2018-02-02 00:00:00
abstract::In this paper, synthesis and characterization of metal complexes [Cu2(L)3]ClO4 (1), [Ga(L)2]NO3·2H2O (2) and [In(L)2]NO3·H2O (3) (HL = 2-acetylpyridine N(4)-phenylthiosemicarbazone) was carried out, including elemental analysis, spectral analysis (IR, UV-vis, NMR), and X-ray crystallography. Complex 1 contains one S-b...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c7md00415j
更新日期:2017-10-09 00:00:00
abstract::Receptor mediated gene delivery to the liver offers advantages in treating genetic disorders such as hemophilia and hereditary tyrosinemia type I (HTI). Prior findings demonstrated that tethering the d-galactose head group to cationic lipids directs genes to the liver via asialoglycoprotein receptors (ASGPRs). In our ...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c7md00503b
更新日期:2017-12-06 00:00:00
abstract::Sphingosine 1-phosphate (S1P) is involved in hyper-proliferative diseases such as cancer and pulmonary arterial hypertension. We have synthesized inhibitors that are selective for the two isoforms of sphingosine kinase (SK1 and SK2) that catalyze the synthesis of S1P. A thiourea adduct of sphinganine (F02) is selectiv...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/C3MD00201B
更新日期:2013-01-01 00:00:00
abstract::In the last three decades, protein and nucleic acid structure determination and comprehension of the mechanisms, leading to their physiological and pathological functions, have become a cornerstone of biomedical sciences. A deep understanding of the principles governing the fates of cells and tissue at the molecular l...
journal_title:MedChemComm
pub_type: 杂志文章,评审
doi:10.1039/c6md00581k
更新日期:2017-01-30 00:00:00
abstract::Herein, we disclose the development of a catalyst- and protecting-group-free microwave-enhanced Friedländer synthesis which permits the single-step, convergent assembly of diverse 8-hydroxyquinolines with greatly improved reaction yields over traditional oil bath heating (increased from 34% to 72%). This rapid synthes...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c6md00381h
更新日期:2016-07-27 00:00:00
abstract::Previous studies have demonstrated that natural steroid compounds containing a peroxide bridge exhibited potential anti-hepatitis B virus activity. To continue our research, a simple and regioselective methodology, using Eosin Y as a clean photosensitized oxidation catalyst, was developed for the synthesis of a peroxi...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c6md00344c
更新日期:2016-10-19 00:00:00
abstract::A library of 33 compounds was screened for potentiation of the antibiotic FR 900098 against the Francisella tularensis surrogate Francisella novicida. From the screen a highly potent 2-oxazoline adjuvant was discovered capable of potentiating FR 900098 with a 1000-fold reduction in MIC against the Francisella sub-spec...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/C6MD00365F
更新日期:2016-01-01 00:00:00
abstract::Twenty-four 14-sulfonamide-tetrandrine derivatives as potential anti-cancer agents were synthesized. The synthetic derivatives were investigated for their cytotoxic activity against human cancer cell lines MDA-MB-231, PC3, WM9, HEL and K562. Initially, the IC50 values (50% inhibitory concentrations) of all of the comp...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c8md00125a
更新日期:2018-05-04 00:00:00
abstract::A series of 4-thiazolidinone derivatives were synthesized and evaluated as novel human dihydroorotate dehydrogenase (hDHODH) inhibitors. Compounds 26 and 31 displayed IC50 values of 1.75 and 1.12 μM, respectively. The structure-activity relationship was summarized. Further binding mode analysis revealed that compound ...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c7md00081b
更新日期:2017-04-26 00:00:00
abstract::The type III secretion system injectisome is a syringe-like multimembrane spanning nanomachine that is essential to the pathogenicity but not viability of many clinically relevant Gram-negative bacteria, such as enteropathogenic Escherichia coli, Salmonella enterica and Pseudomonas aeruginosa. Due to the rise in antib...
journal_title:MedChemComm
pub_type: 杂志文章,评审
doi:10.1039/c9md00146h
更新日期:2019-06-20 00:00:00
abstract::To increase the diversity of estrogen receptor (ER) ligands having novel structures and activities, series of selenophene derivatives with a basic side chain (BSC) were synthesized and their biological activity as subtype-selective antagonists for the ER was explored. Compared with the selenophenes without a BSC, most...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c7md00163k
更新日期:2017-05-24 00:00:00
abstract::Fungal infections directly affect millions of people each year. In addition to the invasive fungal infections of humans, the plants and animals that comprise our primary food source are also susceptible to diseases caused by these eukaryotic microbes. The need for antifungals, not only for our medical needs, but also ...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/C6MD00222F
更新日期:2016-07-01 00:00:00
abstract::We previously reported that troponoid compounds profoundly inhibit replication of herpes simplex virus (HSV)-1 and HSV-2 in cell culture, including acyclovir-resistant mutants. Synthesis of 26 alpha-hydroxylated tropolones (αHTs) led to a preliminary structure-activity relationship highlighting the potency of bi-pheny...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c9md00225a
更新日期:2019-05-30 00:00:00
abstract::Based on the scaffold of astemizole, three novel turn-on fluorescent probes (N1-N3) for human ether-a-go-go-related gene (hERG) potassium channel were developed herein. These probes have reasonable fluorescence properties, acceptable cell toxicity, and potent inhibitory activity, all of which contribute to cell imagin...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c8md00562a
更新日期:2019-02-26 00:00:00
abstract::Much effort has been devoted to targeting agents for imaging and chemotherapy of tumors in cancer research, but there remain significant unmet needs in that area. We have reported a series of preclinical TrkC targeting agents for diagnoses and treatment of metastatic breast cancer; however, with respect to optical ima...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c8md00190a
更新日期:2018-08-03 00:00:00