A series of -(4-chlorophenyl) substituted pyrano[2,3-c]pyrazoles was synthesised and screened for their potential to inhibit kinases and exhibit anticancer activity against primary patient-derived glioblastoma 2D cells and 3D neurospheres. A collection of 10 compounds was evaluated against glioma cell lines, with compound exhibiting promising glioma growth inhibitory properties. Compound was screened against 139 purified kinases and exhibited low micromolar activity against kinase AKT2/PKBβ. AKT signalling is one of the main oncogenic pathways in glioma and is often targeted for novel therapeutics. Indeed, AKT2 levels correlated with glioma malignancy and poorer patient survival. Compound inhibited the 3D neurosphere formation in primary patient-derived glioma stem cells and exhibited potent EC against glioblastoma cell lines. Although exhibiting potency against glioma cells, exhibited significantly less cytotoxicity against non-cancerous cells even at fourfold-fivefold the concentration. Herein we establish a novel biochemical kinase inhibitory function for -(4-chlorophenyl) substituted pyrano[2,3-c]pyrazoles and further report their anti-glioma activity for the first time.KEY MESSAGEAnti-glioma pyrano[2,3-c]pyrazole inhibited the 3D neurosphere formation in primary patient-derived glioma stem cells. also displayed PKBβ/AKT2 inhibitory activity. is nontoxic towards non-cancerous cells.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9683054 | PMC |
| http://dx.doi.org/10.1080/07853890.2022.2123559 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Synthesis of new functionalized bioactive S-substituted indolyl-triazoles as cytotoxic and apoptotic agents through multi-targeted kinase inhibition.
Bioorg Chem
January 2025
Chemistry Department, Faculty of Science, Arish University, Al-Arish 45511, Egypt.
The search for new anticancer compounds is a major focus for researchers in chemistry, biology, and medicine. Cancer affects people of all ages and regions, with rising incidence rates. It does not discriminate by age or gender, making it a significant threat to humanity.
View Article and Find Full Text PDFZn(II)-Stabilized Azo-Anion Radical-Catalyzed Dehydrogenative Synthesis of Olefins.
J Org Chem
December 2024
Department of Chemistry, Indian Institute of Engineering Science and Technology, Shibpur, Botanic Garden, Howrah 711103, India.
Herein, we describe a Zn-catalyzed atom-economical, inexpensive, and sustainable method for preparing a broad spectrum of substituted olefins utilizing alcohols as the main precursor. Using a Zn(II) complex [ZnLCl] () of the redox-noninnocent ligand 2-((4-chlorophenyl)diazenyl)-1,10-phenanthroline (), various ()-olefins were prepared in good yields by coupling alcohols with sulfones and aryl cyanides under an inert atmosphere. Under an aerial atmosphere, vinyl nitriles were isolated in up to 82% yield reacting alcohols with benzyl cyanides in the presence of .
View Article and Find Full Text PDFPyridine Derivatives as Insecticides: Part 6. Design, Synthesis, Molecular Docking, and Insecticidal Activity of 3-(Substituted)methylthio-5,6,7,8-tetrahydroisoquinoline-4-carbonitriles Toward (, 1887).
J Agric Food Chem
September 2024
Department of Chemistry, Faculty of Science, Assiut University, Assiut 71516, Egypt.
Three new series of 3-(substituted)methylthio-4-cyano-5,6,7,8-tetrahydroisoquinolines were designed and synthesized starting from readily available materials, 7-acetyl-4-cyano-1,6-dimethyl-6-hydroxy-8-(4-pyridyl, 3-pyridyl, phenyl, 4-methoxyphenyl, or 4-chlorophenyl)-5,6,7,8-tetrahydrosoquinoline-3(2)-thiones - in high yields and very pure states. Thus, compounds - were reacted with some chloro reagents, namely, -aryl-2-chloroacetamides - and -(naphthalen-2-yl)-2-chloroacetamide () under mild basic conditions to give the first two series of the target compounds, 3-(-aryl)carbamoylmethylthio-5,6,7,8-tetrahydroisoquinoline-4-carbonitriles - and -, respectively. Reaction of compounds , with ethyl chloroacetate under the same conditions gave the other series, 3-ethoxycarbonyl-methylthio-5,6,7,8-tetrahydroisoquinoline-4-carbonitriles ,.
View Article and Find Full Text PDFA solution-processable benzothiazole-substituted formazanate zinc(II) complex designed for a robust resistive memory device.
Dalton Trans
September 2024
Department of Chemistry, Indian Institute of Technology Jodhpur, Rajasthan-342030, India.
A novel mononuclear bis(formazanate)zinc complex (1) based on a redox-active 1-(benzothiazol-2-yl)-5-(2-benzoyl-4-chlorophenyl)-3-phenyl formazan ligand has been synthesized and characterized. Complex 1 was prepared by reacting one equivalent of Zn(OCOCH)·2HO with two equivalents of the corresponding formazan derivative. X-ray crystallography was employed to ascertain the solid-state structure of compound 1, and the analysis revealed a distorted octahedral geometry for the complex where the symmetrical ligands exhibit a preference for coordinating with the zinc center in the 'open' form, generating five-membered chelate rings.
View Article and Find Full Text PDFPan-serotype dengue virus inhibitor JNJ-A07 targets NS4A-2K-NS4B interaction with NS2B/NS3 and blocks replication organelle formation.
Nat Commun
July 2024
Heidelberg University, Medical Faculty Heidelberg, Department of Infectious Diseases, Molecular Virology, Center for Integrative Infectious Disease Research, Heidelberg, Germany.
Article Synopsis
- Dengue fever poses a major health and economic challenge in (sub)tropical regions, with no antiviral treatments currently available.
- JNJ-A07 has been shown to be effective against various dengue virus genotypes by targeting the viral non-structural protein 4B (NS4B) and disrupting important interactions needed for viral replication.
- This research clarifies how JNJ-A07 and a similar compound, NITD-688, inhibit the formation of vesicle packets crucial for dengue virus RNA replication, offering new insights into potential antiviral strategies.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!