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-phenyl side chains. Here, we explore the structure-activity relationship in more detail, with a focus on various biaryl and other lipophilic molecules. Along with our prior structure-function analysis, we present a refined structure-activity relationship that reveals the importance of the lipophilicity and nature of the side chain for potent anti-HSV-1 activity in cells. We expect this new information will help guide future optimization of αHTs as HSV antivirals.
journal_name
Medchemcommjournal_title
MedChemCommauthors
Berkowitz AJ,Franson AD,Gazquez Cassals A,Donald KA,Yu AJ,Garimallaprabhakaran AK,Morrison LA,Murelli RPdoi
10.1039/c9md00225asubject
Has Abstractpub_date
2019-05-30 00:00:00pages
1173-1176issue
7eissn
2040-2503issn
2040-2511pii
c9md00225ajournal_volume
10pub_type
杂志文章相关文献
MedChemComm文献大全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::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::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::Recognition of nucleosides at adenosine receptors (ARs) is supported by multiple X-ray structures, but the structure of an adenine complex is unknown. We examined the selectivity of predicted A1AR and A3AR adenine antagonists that incorporated known agonist affinity-enhancing N6 and C2 substituents. Adenines with A1AR...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c8md00317c
更新日期:2018-10-18 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::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::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::Heat shock factor 1 (HSF1) is a transcription factor that plays key roles in cancer, including providing a mechanism for cell survival under proteotoxic stress. Therefore, inhibition of the HSF1-stress pathway represents an exciting new opportunity in cancer treatment. We employed an unbiased phenotypic screen to disc...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c6md00159a
更新日期:2016-08-01 00:00:00
abstract::Many reports have suggested that NRP-1 acts as a co-receptor for VEGF-A165 and boosts tumour growth and metastasis. This NRP-1, due to its important role in tumour progression, triggered interest in the design of new molecules able to significantly inhibit NRP-1/VEGF-A165 interaction to suppress pathological angiogene...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c8md00537k
更新日期:2019-01-25 00:00:00
abstract::The phenol of 1-(3-(1H-imidazol-1-yl)propyl)-3-(4-hydroxy-3-methoxyphenyl)thiourea was selectively carbon-11 labelled to generate [11C]PBD150 in 7.3% yield from [11C]methyl triflate (non-decay corrected; radiochemical purity ≥95%, specific activity = 5.7 Ci/µmol, n=5). Evaluation of [11C]PBD150 by small animal PET ima...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/C5MD00148J
更新日期:2015-06-01 00:00:00
abstract::2-Arylethynyl derivatives of (N)-methanocarba adenosine 5'-uronamides are selective A3AR (adenosine receptor) agonists. Here we substitute a 1,2,3-triazol-1-yl linker in place of the rigid, linear ethynyl group to eliminate its potential metabolic liability. Docking of nucleosides containing possible short linker moie...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/C4MD00571F
更新日期:2015-01-01 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::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::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::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::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::Based on structure modification and a high-throughput Jurkat-Lat cell screening model, we found that GIBH-LRA002, ethyl-2-amino-3-cyano-9-methyl-4-(trifluoromethyl)-4,9-dihydropyrano[2,3-b]indole-4-carboxylate, effectively reactivated the latent proviruses in a Jurkat-Lat cell line and primary CD4+ T cells from both c...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c7md00327g
更新日期:2017-07-25 00:00:00
abstract::Herein, we present the design and synthesis of a series of novel heterocyclic derivatives of (-)-borneol and (-)-isoborneol as potent inhibitors of the influenza A virus. All compounds were tested for their toxicity against MDCK cells and for virus-inhibiting activity against the influenza virus A/Puerto Rico/8/34 (H1...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c6md00657d
更新日期:2017-03-03 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::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::Herein we continued our previous work on the development of CB2 ligands, reporting the design and synthesis of a series of benzimidazole-containing derivatives that were explored as selective CB2 ligands with binding affinity towards both CB1 and CB2 receptors. Seven out of eighteen compounds exhibited preferential bi...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c8md00461g
更新日期:2018-10-10 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::Tuberculosis (TB) is an epidemic disease and the growing burden of multidrug-resistant (MDR) TB world wide underlines the need to discover new drugs to treat the disease. Mycobacterium tuberculosis (Mtb) is the etiological agent of most cases of TB. Mtb is difficult to treat, in part, due to the presence of a sturdy h...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/C5MD00376H
更新日期:2016-01-01 00:00:00
abstract::In the present work, coumarin based pyrazolines (7a-g) have been synthesized and investigated for their in vitro and in vivo anti-inflammatory potential. Amongst the synthesized compounds, compounds 7a, 7d and 7f exhibited significant in vitro anti-inflammatory activity as compared to the standard etoricoxib. Keeping ...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c8md00457a
更新日期:2019-01-23 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::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::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::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::Intrinsic and acquired resistance to conventional and targeted therapeutics is a fundamental reason for treatment failure in many cancer patients. Targeted approaches to overcome chemoresistance as well as resistance to targeted approaches require in depth understanding of the underlying molecular mechanisms. The anti...
journal_title:MedChemComm
pub_type: 杂志文章,评审
doi:10.1039/c6md00394j
更新日期:2016-10-21 00:00:00
abstract::Bruton's tyrosine kinase (BTK) plays a critical role in B cell receptor (BCR)-mediated signaling pathways responsible for the development and function of B cells, which makes it an attractive target for the treatment of many types of B-cell malignancies. Herein, a series of N5-substituted 6,7-dioxo-6,7-dihydropteridin...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c8md00019k
更新日期:2018-03-13 00:00:00