Novel 1,5-diphenyl-6-substituted 1H-pyrazolo[3,4-d]pyrimidin-4(5H)-ones induced apoptosis in RKO colon cancer cells
Author | Malki, Ahmed |
Author | Ashour, Hayam M. A. |
Author | Elbayaa, Rasha Y. |
Author | Issa, Doaa A. E. |
Author | Aziz, Hassan A. |
Author | Chen, Xiaozhuo |
Available date | 2021-04-22T13:00:31Z |
Publication Date | 2016 |
Publication Name | Journal of Enzyme Inhibition and Medicinal Chemistry |
Resource | Scopus |
Abstract | Novel 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. |
Language | en |
Publisher | Taylor 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 |
Type | Article |
Pagination | 1286-1299 |
Issue Number | 6 |
Volume Number | 31 |
Files in this item
Files | Size | Format | View |
---|---|---|---|
There are no files associated with this item. |
This item appears in the following Collection(s)
-
Biomedical Sciences [697 items ]