Identification of new scaffolds with anti-tumor action toward human glioblastoma cells

Ellert-Miklaszewska, Aleksandra; Dallavalle, Sabrina; Musso, Loana; Martinet, Nadine; Wojnicki, Kamil; Kamińska, Bożena

doi:10.1039/c6md00477f

Cited by 5 publications

(3 citation statements)

References 31 publications

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“…To identify a new scaffold with potential anti-GBM activity against resistant cell lines, Ellert-Miklaszewska et al screened three diverse groups of scaffolds with 4-vinylbiphenyl skeleton, 3-arylidene-oxindole, and isothiazolonaphthoquinone core substitutions. 60 The identification of the scaffold was carried out by screening the compounds from the various series over LN18 and T98 GBM cell lines. Among all the compounds, 58 , with a HDAC inhibitor architecture, showed significant cell growth inhibition of more than 70% against the LN18 and T98 cell lines.…”

Section: Recent Medicinal Chemistry Campaignsmentioning

confidence: 99%

“…Additionally, the selectivity profile of all compounds was studied for HDAC1 and HDAC6, where 57 was found to be non-selective against HDAC1 and HDAC6. To identify a new scaffold with potential anti-GBM activity against resistant cell lines, Ellert-Miklaszewska et al screened three diverse groups of scaffolds with 4-vinylbiphenyl skeleton, 3-arylidene-oxindole, and isothiazolonaphthoquinone core substitutions . The identification of the scaffold was carried out by screening the compounds from the various series over LN18 and T98 GBM cell lines.…”

Section: Recent Medicinal Chemistry Campaignsmentioning

confidence: 99%

“…The scientific literature covered in this Perspective indicates that kinases (phosphoinositide 3-kinases (PI3K), − focal adhesion kinase (FAK), − DYRK, and 3-phosphoinositide-dependent kinase 1 (PDK1) , ) have been extensively targeted through the pragmatic design of heterocyclic compounds (triazines, pyrimidines, indoles, oxoindoles, 6:5 fused heterocycles, and others). Notably, these research groups have conducted a series of studies on kinase inhibitors as anti-GBM agents, and their efforts have led to the identification of potent adducts worthy of detailed investigation. − Another target that has been reasonably utilized for the construction of anti-GBM agents in the recent past is histone deacetylase (HDAC). − The drug design strategies for HDAC inhibitors discussed in this Perspective clearly depict the flexibility of the three-component HDAC inhibitory model. Specifically, the structural alteration of the surface recognition part of the HDAC inhibitory pharmacophore has been the main focus of the medicinal chemist to extract anti-GBM effects through the inhibition of several HDAC isoforms.…”

Section: Introductionmentioning

confidence: 99%

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Glioblastoma: Current Status, Emerging Targets, and Recent Advances

et al. 2022

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Glioblastoma (GBM) is a highly malignant brain tumor characterized by a heterogeneous population of genetically unstable and highly infiltrative cells that are resistant to chemotherapy. Although substantial efforts have been invested in the field of anti-GBM drug discovery in the past decade, success has primarily been confined to the preclinical level, and clinical studies have often been hampered due to efficacy-, selectivity-, or physicochemical property-related issues. Thus, expansion of the list of molecular targets coupled with a pragmatic design of new small-molecule inhibitors with central nervous system (CNS)-penetrating ability is required to steer the wheels of anti-GBM drug discovery endeavors. This Perspective presents various aspects of drug discovery (challenges in GBM drug discovery and delivery, therapeutic targets, and agents under clinical investigation). The comprehensively covered sections include the recent medicinal chemistry campaigns embarked upon to validate the potential of numerous enzymes/proteins/receptors as therapeutic targets in GBM.

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Section: Recent Medicinal Chemistry Campaignsmentioning

confidence: 99%

Section: Recent Medicinal Chemistry Campaignsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Glioblastoma: Current Status, Emerging Targets, and Recent Advances

et al. 2022

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Recent Advances in the Synthesis and Reactivity of Isothiazoles

2019

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Isothiazoles represent an important class of five‐membered sulfur heterocycles that are widely utilized in medicinal chemistry and organic synthesis due to the unique properties of two electronegative heteroatoms in a 1,2‐relationship. However, in contrast to other 1,2‐azoles, the facile assembly of isothiazoles has always been considered a substantial challenge. In the last decade, major advances have taken place in the fields of synthesis and functionalization of isothiazoles that make them accessible to a wide range of interested chemists through unprecedented pathways. New condensation methods have emerged that address the challenges posed by unstable thiohydroxylamine. New metal‐catalyzed approaches have been reported that deliver densely decorated isothiazoles bearing various sensitive functional groups. New functionalization strategies have been developed through both cross‐coupling and direct C−H activation chemistry. Finally, the emergence of novel heterocyclic architectures based on isothiazole opens the door for future investigations of this versatile heterocyclic scaffold. This review covers the period from January 2004 to December 2018 and is intended as a sequel to the review on isoxazoles, which represent another class of synthetically‐important 1,2‐azoles (see Adv. Synth. Catal. 2015, 357, 2583–2614).

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