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AuthorMalki, Ahmed
AuthorAshour, Hayam M. A.
AuthorElbayaa, Rasha Y.
AuthorIssa, Doaa A. E.
AuthorAziz, Hassan A.
AuthorChen, Xiaozhuo
Available date2021-04-22T13:00:31Z
Publication Date2016
Publication NameJournal of Enzyme Inhibition and Medicinal Chemistry
ResourceScopus
URIhttp://dx.doi.org/10.3109/14756366.2015.1118686
URIhttp://hdl.handle.net/10576/18342
AbstractNovel 1,5-diphenyl-6-substituted-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-ones were synthesized and characterized. All compounds were screened for their anti-proliferative activities in five different cancer cell lines. The results showed that compounds 7a and 7b comprising aminoguanidino or guanidino moiety at position 6 inhibited proliferation of RKO colon cancer cells with IC50 of 8 and 4 ?M, respectively. Compounds 7a and 7b induced apoptosis in RKO cells, which was confirmed by TUNEL and annexin V-FITC assays. Flow cytometric analysis indicated that compounds 7a and 7b arrested RKO cells in the G1 phase and the most active compound 7b increased levels of p53, p21, Bax, ERK1/2 and reduced levels of Bcl2 and Akt. Compound 7b also activates release of cytochrome c, which is consistent with activation of caspase-9. Additionally, compound 7b increased caspase-3 activity and cleaved PARP-1 in RKO cells. Collectively, these findings could establish a molecular basis for the development of new anti-cancer agents.
Languageen
PublisherTaylor and Francis Ltd
Subject(4 oxo 1,5 diphenyl 4,5 dihydro 1h pyrazolo[3,4 d]pyrimidin 6 yl)guanidine
(4 oxo 1,5 diphenyl 4,5 dihydro 1h pyrazolo[3,4 d]pyrimidin 6 ylamino)guanidine
1,5 diphenyl 6 (propylamino) 1h pyrazolo[3,4 d]pyrimidin 4(5h) one
1,5 diphenyl 6 substituted 1h pyrazolo[3,4 d]pyrimidin 4(5h) one derivative
6 (1 hydroxy 2 methylpropan 2 ylamino) 1,5 diphenyl 1h pyrazolo[3,4 d]pyrimidin 4(5h) one
6 (2 aminoethylamino) 1,5 diphenyl 1h pyrazolo[3,4 d]pyrimidin 4(5h) one
6 (2 hydroxyethylamino) 1,5 diphenyl 1h pyrazolo[3,4 d]pyrimidin 4(5h) one
6 (2 morpholinoethylamino) 1,5 diphenyl 1h pyrazolo[3,4 d]pyrimidin 4(5h) one
6 (benzyllamino) 1,5 diphenyl 1h pyrazolo[3,4 d]pyrimidin 4(5h) one
6 (cyclohexylamino) 1,5 diphenyl 1h pyrazolo[3,4 d]pyrimidin 4(5h) one
6 (methylsulfanyl) 1,5 diphenyl 1h pyrazolo[3,4 d]pyrimidin 4(5h) one
6 (methylsulfonyl) 1,5 diphenyl 1h pyrazolo[3,4 d]pyrimidin 4(5h) one
6 ethoxy 1,5 diphenyl 1h pyrazolo[3,4 d]pyrimidin 4(5h) one
6 hydrazino 1,5 diphenyl 1h pyrazolo[3,4 d]pyrimidin 4(5h)one
6 [1,3 dihydroxy 2 (hydroxymethyl)propan 2 ylamino] 1,5 diphenyl 1h pyrazolo[3,4 d]pyrimidin 4(5h) one
6 [2 (3,,5 trimethoxybenzylidene)hydrazino] 1,5 diphenyl 1h pyrazolo[3,4 d]pyrimidin 4(5h) one
6 [2 (3,4 dimethoxybenzylidene)hydrazino] 1,5 diphenyl 1h pyrazolo[3,4 d]pyrimidin 4(5h) one
6 [2 (3,4 dimethoxyphenyl)ethylamino] 1,5 diphenyl 1h pyrazolo[3,4 d]pyrimidin 4(5h) one
6 [2 (4 methoxybenzylidene)hydrazino] 1,5 diphenyl 1h pyrazolo[3,4 d]pyrimidin 4(5h) one
6 [2 (pyrrolidin 1 yl)ethylamino] 1,5 diphenyl 1h pyrazolo[3,4 d]pyrimidin 4(5h) one
antineoplastic agent
caspase 3
caspase 9
cisplatin
cytochrome c
n' (4 oxo 1,5 diphenyl 4,5 dihydro 1h pyrazolo[3,4 d]pyrimidin 6 yl) 4 methoxy benzenesulfohydrazide
n' (4 oxo 1,5 diphenyl 4,5 dihydro 1h pyrazolo[3,4 d]pyrimidin 6 yl) 4 methoxybenzohydrazide
n' (4 oxo 1,5 diphenyl 4,5 dihydro 1h pyrazolo[3,4 d]pyrimidin 6 yl)benzenesulfohydrazide
n' (4 oxo 1,5 diphenyl 4,5 dihydro 1h pyrazolo[3,4 d]pyrimidin 6 yl)benzohydrazide
pyrimidine derivative
unclassified drug
antineoplastic agent
pyrimidinone derivative
A431 cell line
antineoplastic activity
antiproliferative activity
apoptosis
Article
cancer cell
cell proliferation
colon cancer
cytotoxicity test
DNA fragmentation
drug cytotoxicity
drug screening
drug synthesis
enzyme activation
enzyme linked immunosorbent assay
enzyme linked immunospot assay
flow cytometry
H1299 cell line
HepG2 cell line
human
human cell
IC50
in vitro study
liver cancer cell line
lung cancer cell line
MCF 7 cell line
priority journal
proton nuclear magnetic resonance
RKO cell line
squamous cell carcinoma cell line
structure activity relation
TUNEL assay
Western blotting
apoptosis
chemistry
colon tumor
drug effects
pathology
spectroscopy
tumor cell line
Antineoplastic Agents
Apoptosis
Cell Line, Tumor
Colonic Neoplasms
Drug Screening Assays, Antitumor
Humans
Pyrimidinones
Spectrum Analysis
TitleNovel 1,5-diphenyl-6-substituted 1H-pyrazolo[3,4-d]pyrimidin-4(5H)-ones induced apoptosis in RKO colon cancer cells
TypeArticle
Pagination1286-1299
Issue Number6
Volume Number31


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