Show simple item record

AuthorMalki, Ahmed
AuthorAshour, Hayam M.A.
AuthorElbayaa, Rasha Y.
AuthorIssa, Doaa A. E.
AuthorAziz, Hassan A.
AuthorChen, Xiaozhuo
Available date2016-10-06T11:19:29Z
Publication Date2015-12-18
Publication NameJournal of Enzyme Inhibition and Medicinal Chemistry
Identifierhttp://dx.doi.org/10.3109/14756366.2015.1118686
CitationAhmed Malki, Hayam M. A. Ashour, Rasha Y. Elbayaa, Doaa A. E. Issa, Hassan A. Aziz & Xiaozhuo Chen (2016) Novel 1,5-diphenyl-6-substituted 1H-pyrazolo[3,4- d]pyrimidin-4(5H)-ones induced apoptosis in RKO colon cancer cells, Journal of Enzyme Inhibition and Medicinal Chemistry, 31:6, 1286-1299.
ISSN1475-6366
URIhttp://hdl.handle.net/10576/4833
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 μM, 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 & Francis
SubjectApoptosis
caspase-3
PARP-1
pyrazolo[3,4- d]pyrimidin-4(5H)-ones
p53
RKO
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
ESSN1475-6374
dc.accessType Abstract Only


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record