Abstract:
:N-Myristoyltransferase (NMT) represents an attractive drug target in parasitic infections such as malaria due to its genetic essentiality and amenability to inhibition by drug-like small molecules. Scaffold simplification from previously reported inhibitors containing bicyclic cores identified phenyl derivative 3, providing a versatile platform to study the effects of substitution on the scaffold, which yielded pyridyl 19. This molecule exhibited improved enzyme and cellular potency, and reduced lipophilicity compared to inhibitor 3. Further structure-based inhibitor design led to the discovery of 30, the most potent inhibitor in this series, which showed single-digit nM enzyme affinity and sub-μM anti-plasmodial activity.
journal_name
Medchemcommjournal_title
MedChemCommauthors
Yu Z,Brannigan JA,Rangachari K,Heal WP,Wilkinson AJ,Holder AA,Leatherbarrow RJ,Tate EWdoi
10.1039/c5md00242gsubject
Has Abstractpub_date
2015-10-08 00:00:00pages
1767-1772issue
10eissn
2040-2503issn
2040-2511pii
c5md00242gjournal_volume
6pub_type
杂志文章相关文献
MedChemComm文献大全abstract::The dopamine D3 receptor (D3R) is a proven therapeutic target for the treatment of neurological and neuropsychiatric disorders. In particular, D3R-selective ligands that can eliminate side effects associated with dopamine D2 receptor (D2R) therapeutics have been validated. However, the high homology in signaling pathw...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c8md00237a
更新日期:2018-06-14 00:00:00
abstract::A series of novel indazole-pyrone hybrids were synthesized by a one pot reaction between N-alkyl-6(5)-nitroindazoles and 2-pyrone (4-hydroxy-6-methyl-2H-pyran-2-one) using indium or stannous chloride as the reducing system in the presence of acetic acid in tetrahydrofuran. The hybrid molecules were obtained in good to...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c8md00475g
更新日期:2018-11-19 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::DNA-encoded libraries of chemically synthesized compounds are an important small molecule screening technology. The synthesis of encoded compounds in solution is currently restricted to a few DNA-compatible and water-tolerant reactions. Encoded compound synthesis of short DNA-barcodes covalently connected to solid sup...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c9md00042a
更新日期:2019-02-26 00:00:00
abstract::The natural products colchicine and combretastatin A-4 (CA4) have provided inspiration for the discovery and development of a wide array of derivatives and analogues that inhibit tubulin polymerization through a binding interaction at the colchicine site on β-tubulin. A water-soluble phosphate prodrug salt of CA4 (ref...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c8md00322j
更新日期:2018-08-24 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::Diabetes mellitus is a chronic, complex and multifactorial disease associated characteristically with hyperglycemia. One of the most recently approved antidiabetic drug classes for clinical use are sodium-glucose cotransporter type 2 (SGLT-2) inhibitors. SGLT-2 is a protein expressed in the kidneys, responsible for gl...
journal_title:MedChemComm
pub_type: 杂志文章,评审
doi:10.1039/c8md00183a
更新日期:2018-06-06 00:00:00
abstract::A focused library of 24 N-aryl urea derivatives was prepared and evaluated against serine esterases of Mycobacterium tuberculosis (Mtb) Rv3802c and Mtb Ag85C. The members of the library were evaluated for both selectivity and mode of inhibition. Furan-based urea derivative 6c was found to be the most potent non-covale...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c9md00122k
更新日期:2019-06-04 00:00:00
abstract::Bile acids have emerged as strong signaling molecules capable of influencing various biological processes like inflammation, apoptosis, cancer progression and atherosclerosis depending on their chemistry. In the present study, we investigated the effect of major hydrophobic bile acids lithocholic acid (LCA) and deoxyc...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c7md00475c
更新日期:2017-10-31 00:00:00
abstract::Urinary tract infections (UTIs) are amongst the most common and prevalent infectious diseases worldwide, with uropathogenic Escherichia coli (UPEC) reported as the main causative pathogen. Fluoroquinolone antibiotics are commonly used to treat UTIs but for infections involving UPEC biofilms, which are commonly associa...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c9md00062c
更新日期:2019-02-25 00:00:00
abstract::A combinatorial library of 6 × 106 cyclic peptides was synthesized in the one bead-two compound format, with each bead displaying a unique cyclic peptide on its surface and a linear peptide encoding tag in its interior. Screening of the library against K-Ras identified compounds that bound K-Ras with submicromolar aff...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/C2MD20329D
更新日期:2013-02-01 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 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::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::The high storage capacities and excellent biocompatibilities of zinc(ii) metal-organic frameworks (Zn-MOFs) have made them outstanding candidates as drug delivery carriers. Recent studies on the pH-responsive processes based on carrier-drug interactions have proven them to be the most efficient and effective way to co...
journal_title:MedChemComm
pub_type: 杂志文章,评审
doi:10.1039/c9md00400a
更新日期:2019-10-17 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::Glutamine and tyrosine-based amino acid conjugates of monocarboxylate transporter types 1 and 2 inhibitors (MCT1/2) were designed, synthesized and evaluated for their potency in blocking the proliferation of a human B lymphoma cell line that expresses the transporters Asct2, LAT1 and MCT1. Appropriate placement of an ...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/C5MD00579E
更新日期:2016-05-01 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::Rigidification of the isobutyl side chain of drug-like AT2 receptor agonists and antagonists that are structurally related to the first reported selective AT2 receptor agonist 1 (C21) delivered bioactive indane derivatives. Four enantiomer pairs were synthesized and the enantiomers were isolated in an optical purity >...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c9md00402e
更新日期:2019-11-18 00:00:00
abstract::The benzophenone scaffold represents a ubiquitous structure in medicinal chemistry because it is found in several naturally occurring molecules which exhibit a variety of biological activities, such as anticancer, anti-inflammatory, antimicrobial, and antiviral. In addition, various synthetic benzophenone motifs are p...
journal_title:MedChemComm
pub_type: 杂志文章,评审
doi:10.1039/c8md00300a
更新日期:2018-08-23 00:00:00
abstract::Ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1, EC 3.1.4.1) is a metalloenzyme that belongs to the NPP family, which comprises seven subtypes (NPP1-7). NPP1 hydrolyzes a wide range of phosphodiester bonds, e.g. in nucleoside triphosphates, (cyclic) dinucleotides, and nucleotide sugars yielding nucleoside 5'...
journal_title:MedChemComm
pub_type: 杂志文章,评审
doi:10.1039/c7md00015d
更新日期:2017-02-09 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::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
abstract::Periodontal disease is an oral chronic immune-inflammatory disease highly prevalent worldwide that is initiated by specific oral bacterial species leading to local and systemic effects. The development of new preventive/therapeutic strategies to specifically target oral periodontopathogens without perturbing oral micr...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c9md00074g
更新日期:2019-06-10 00:00:00
abstract::Porphyrins are tetrapyrrolic macrocyclic ligands known for their affinity towards neoplastic tissues and once radiolabeled with a suitable diagnostic radioisotope could potentially be used for the imaging of tumorous lesions. In the present study, an unsymmetrically substituted porphyrin derivative namely 5-(p-amino-p...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c8md00559a
更新日期:2019-02-22 00:00:00
abstract::Recent studies point towards the possible disadvantages of using hydroxamic acid-based zinc-binding groups in HDAC inhibitors due to e.g. mutagenicity issues. In this work, we elaborated on our previously developed Tubathian series, a class of highly selective thiaheterocyclic HDAC6 inhibitors, by replacing the benzoh...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c8md00107c
更新日期:2018-05-18 00:00:00
abstract::Human African trypanosomiasis (HAT), also known as African sleeping sickness, is caused by parasitic protozoa of the genus Trypanosoma. As the disease progresses, the parasites cross the blood brain barrier and are lethal for the patients if the disease is left untreated. Current therapies suffer from several drawback...
journal_title:MedChemComm
pub_type: 杂志文章,评审
doi:10.1039/c7md00280g
更新日期:2017-07-31 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::Malaria is a serious tropical disease that kills thousands of people every year, mainly in Africa, due to Plasmodium falciparum infections. Salirasib is a promising cancer drug candidate that interferes with the post-translational modification of Ras. This S-farnesyl thiosalicylate inhibits isoprenylcysteine carboxyl ...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c9md00298g
更新日期:2019-06-21 00:00:00
abstract::Tuberculosis is an ever-evolving infectious disease that urgently needs new drugs. In the search for new antituberculosis agents, a library of 3-cinnamoyl-4-hydroxy-6-methyl-2H-pyran-2-ones (CHPs) (2a-2y) was synthesized and evaluated against a standard virulent laboratory strain of Mycobacterium tuberculosis H37Rv. O...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c7md00366h
更新日期:2017-12-06 00:00:00