Matches in SemOpenAlex for { <https://semopenalex.org/work/W2912981317> ?p ?o ?g. }
- W2912981317 endingPage "303" @default.
- W2912981317 startingPage "291" @default.
- W2912981317 abstract "Nerve growth factor receptor (NGFR), a member of kinase protein, is emerging as an important target for Glioblastoma (GBM) treatment. Overexpression of NGFR is observed in many metastatic cancers including GBM, promoting tumor migration and invasion. Hydrazones have been reported to effectively interact with receptor tyrosine kinases (RTKs). We report herein the synthesis of 23 arylhydrazones of active methylene compounds (AHAMCs) compounds and their anti-proliferative activity against GBM cell lines, LN229 and U87. Compound R234, 2-(2-(2,4-dioxopentan-3-ylidene)hydrazineyl)benzonitrile, was identified as the most active anti-neoplastic compound, with the IC50 value ranging 87 μM - 107 μM. Molecular docking simulations of the synthesized compounds into the active site of tyrosine receptor kinase A (TrkA), demonstrated a strong binding affinity with R234 and concurs well with the obtained biological results. R234 was found to be a negative regulator of PI3K/Akt/mTOR pathway and an enhancer of p53 expression. In addition, R234 treated GBM cells exhibited the downregulation of cyclins, cyclin-dependent kinases and other key molecules involved in cell cycle such as CCNE, E2F, CCND, CDK6, indicating that R234 induces cell cycle arrest at G1/S. R234 also exerted its apoptotic effects independent of caspase3/7 activity, in both cell lines. In U87 cells, R234 induced oxidative effects whereas LN229 cells annulled oxidative stress. The study thus concludes that R234, being a negative modulator of RTKs and cell cycle inhibitor, may represent a novel class of anti-GBM drugs." @default.
- W2912981317 created "2019-02-21" @default.
- W2912981317 creator A5006109884 @default.
- W2912981317 creator A5008410351 @default.
- W2912981317 creator A5008875824 @default.
- W2912981317 creator A5015029563 @default.
- W2912981317 creator A5023911627 @default.
- W2912981317 creator A5026230936 @default.
- W2912981317 creator A5034254426 @default.
- W2912981317 creator A5057625030 @default.
- W2912981317 creator A5059431218 @default.
- W2912981317 creator A5074598231 @default.
- W2912981317 date "2019-03-01" @default.
- W2912981317 modified "2023-09-23" @default.
- W2912981317 title "2-(2-(2,4-dioxopentan-3-ylidene)hydrazineyl)benzonitrile as novel inhibitor of receptor tyrosine kinase and PI3K/AKT/mTOR signaling pathway in glioblastoma" @default.
- W2912981317 cites W136104837 @default.
- W2912981317 cites W1639582946 @default.
- W2912981317 cites W1754197334 @default.
- W2912981317 cites W1966803171 @default.
- W2912981317 cites W1969479602 @default.
- W2912981317 cites W1970238622 @default.
- W2912981317 cites W1972508656 @default.
- W2912981317 cites W1974899939 @default.
- W2912981317 cites W1977260182 @default.
- W2912981317 cites W1977674772 @default.
- W2912981317 cites W1980352202 @default.
- W2912981317 cites W1985320052 @default.
- W2912981317 cites W1985772559 @default.
- W2912981317 cites W1988524789 @default.
- W2912981317 cites W1988807053 @default.
- W2912981317 cites W1991348277 @default.
- W2912981317 cites W1993563727 @default.
- W2912981317 cites W1994525260 @default.
- W2912981317 cites W2005661588 @default.
- W2912981317 cites W2006890215 @default.
- W2912981317 cites W2007147192 @default.
- W2912981317 cites W2007206489 @default.
- W2912981317 cites W2014380713 @default.
- W2912981317 cites W2017455950 @default.
- W2912981317 cites W2025183726 @default.
- W2912981317 cites W2033329907 @default.
- W2912981317 cites W2034277114 @default.
- W2912981317 cites W2036878177 @default.
- W2912981317 cites W2037173620 @default.
- W2912981317 cites W2039845745 @default.
- W2912981317 cites W2042215590 @default.
- W2912981317 cites W2042229191 @default.
- W2912981317 cites W2043024617 @default.
- W2912981317 cites W2043194375 @default.
- W2912981317 cites W2048591564 @default.
- W2912981317 cites W2051381895 @default.
- W2912981317 cites W2053245283 @default.
- W2912981317 cites W2053654862 @default.
- W2912981317 cites W2060168444 @default.
- W2912981317 cites W2061760261 @default.
- W2912981317 cites W2068889110 @default.
- W2912981317 cites W2070772962 @default.
- W2912981317 cites W2075183887 @default.
- W2912981317 cites W2076363741 @default.
- W2912981317 cites W2082878515 @default.
- W2912981317 cites W2084980673 @default.
- W2912981317 cites W2102127553 @default.
- W2912981317 cites W2103816610 @default.
- W2912981317 cites W2109816625 @default.
- W2912981317 cites W2110795584 @default.
- W2912981317 cites W2115187133 @default.
- W2912981317 cites W2115782808 @default.
- W2912981317 cites W2127485202 @default.
- W2912981317 cites W2134989772 @default.
- W2912981317 cites W2135193909 @default.
- W2912981317 cites W2148608910 @default.
- W2912981317 cites W2165925657 @default.
- W2912981317 cites W2166726813 @default.
- W2912981317 cites W2170232165 @default.
- W2912981317 cites W2170367762 @default.
- W2912981317 cites W2171881796 @default.
- W2912981317 cites W2183989909 @default.
- W2912981317 cites W2216221547 @default.
- W2912981317 cites W2276825528 @default.
- W2912981317 cites W2321407094 @default.
- W2912981317 cites W2326239317 @default.
- W2912981317 cites W2411930441 @default.
- W2912981317 cites W2519786994 @default.
- W2912981317 cites W2562236228 @default.
- W2912981317 cites W2738485098 @default.
- W2912981317 cites W2752375057 @default.
- W2912981317 cites W2795693351 @default.
- W2912981317 doi "https://doi.org/10.1016/j.ejmech.2019.01.021" @default.
- W2912981317 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30731398" @default.
- W2912981317 hasPublicationYear "2019" @default.
- W2912981317 type Work @default.
- W2912981317 sameAs 2912981317 @default.
- W2912981317 citedByCount "46" @default.
- W2912981317 countsByYear W29129813172019 @default.
- W2912981317 countsByYear W29129813172020 @default.
- W2912981317 countsByYear W29129813172021 @default.
- W2912981317 countsByYear W29129813172022 @default.
- W2912981317 countsByYear W29129813172023 @default.