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 excellent yields (72-92%) and characterized by NMR and single crystal X-ray diffraction. Nineteen compounds were tested in vitro against both Leishmania donovani (MHOM/ET/67/HU3, also called LV9) axenic and intramacrophage amastigotes. Among all, five compounds showed anti-leishmanial activity against intracellular L. donovani with an IC50 in the range of 2.25 to 62.56 μM. 3-(1-(3-Chloro-2-ethyl-2H-indazol-6-ylamino)ethylidene)-6-methyl-3H-pyran-2,4-dione 6f was found to be the most active compound for axenic amastigotes and intramacrophage amastigotes of L. donovani with IC50 values of 2.48 ± 1.02 μM and 2.25 ± 1.89 μM, respectively. However, the cytotoxicity of the most promising compound justifies further pharmacomodulations.
journal_name
Medchemcommjournal_title
MedChemCommauthors
El Ghozlani M,Bouissane L,Berkani M,Mojahidi S,Allam A,Menendez C,Cojean S,Loiseau PM,Baltas M,Rakib EMdoi
10.1039/c8md00475gsubject
Has Abstractpub_date
2018-11-19 00:00:00pages
120-127issue
1eissn
2040-2503issn
2040-2511pii
c8md00475gjournal_volume
10pub_type
杂志文章相关文献
MedChemComm文献大全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::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::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::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::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::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::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::N-Acylethanolamine acid amidase (NAAA) is one of the key enzymes involved in the degradation of fatty acid ethanolamides (FAEs), especially for palmitoylethanolamide (PEA). Pharmacological blockage of NAAA restores PEA levels, providing therapeutic benefits in the management of inflammation and pain. In the current wo...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c8md00432c
更新日期:2018-12-18 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::[This corrects the article DOI: 10.1039/C0MD00060D.]. ...
journal_title:MedChemComm
pub_type: 已发布勘误
doi:10.1039/c8md90010h
更新日期:2018-03-19 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::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::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::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::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::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::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 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::[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::β-Carbolines have been assessed for osteoclastogenesis. However, their effect on osteoblasts during estrogen deficiency is still unclear. Here, a series of novel piperazine and tetrazole tag β-carbolines have been synthesized and examined for osteoblast differentiation in vitro. In vitro data suggest that compound 8g ...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/c8md00109j
更新日期:2018-06-12 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::The benzisoxazole analogs represent one of the privileged structures in medicinal chemistry and there has been an increasing number of studies on benzisoxazole-containing compounds. The unique benzisoxazole scaffold also exhibits an impressive potential as antimicrobial, anticancer, anti-inflammatory, anti-glycation a...
journal_title:MedChemComm
pub_type: 杂志文章,评审
doi:10.1039/c7md00449d
更新日期:2017-10-31 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::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::It was previously reported that 6β-aminomorphinan derivatives show high affinity for opiate receptors. Novel 6β-heteroarylamidomorphinanes were designed based on the MOR selective antagonist NAP. The 6β-aminomorphinanes were prepared with stereoselective Mitsunobu reaction and subsequently acylated with nicotinic acid...
journal_title:MedChemComm
pub_type: 杂志文章
doi:10.1039/C6MD00450D
更新日期:2017-01-01 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::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::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