Novel 1,5-diphenyl-6-substituted 1H-pyrazolo[3,4-d]pyrimidin-4(5H)-ones induced apoptosis in RKO colon cancer cells

Ahmed Malki, Hayam M.A. Ashour, Rasha Y. Elbayaa, Doaa A.E. Issa, Hassan Abdel-Aziz, Xiaozhuo Chen

Research output: Contribution to journalArticle

3 Citations (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 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.

Original languageEnglish (US)
Pages (from-to)1286-1299
Number of pages14
JournalJournal of Enzyme Inhibition and Medicinal Chemistry
Volume31
Issue number6
DOIs
StatePublished - Nov 1 2016
Externally publishedYes

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Colonic Neoplasms
Apoptosis
Caspase 9
Fluorescein-5-isothiocyanate
Annexin A5
In Situ Nick-End Labeling
G1 Phase
Cytochromes c
Caspase 3
Inhibitory Concentration 50
Neoplasms
Cell Line
diphenyl

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Drug Discovery

Cite this

Novel 1,5-diphenyl-6-substituted 1H-pyrazolo[3,4-d]pyrimidin-4(5H)-ones induced apoptosis in RKO colon cancer cells. / Malki, Ahmed; Ashour, Hayam M.A.; Elbayaa, Rasha Y.; Issa, Doaa A.E.; Abdel-Aziz, Hassan; Chen, Xiaozhuo.

In: Journal of Enzyme Inhibition and Medicinal Chemistry, Vol. 31, No. 6, 01.11.2016, p. 1286-1299.

Research output: Contribution to journalArticle

Malki, Ahmed ; Ashour, Hayam M.A. ; Elbayaa, Rasha Y. ; Issa, Doaa A.E. ; Abdel-Aziz, Hassan ; Chen, Xiaozhuo. / Novel 1,5-diphenyl-6-substituted 1H-pyrazolo[3,4-d]pyrimidin-4(5H)-ones induced apoptosis in RKO colon cancer cells. In: Journal of Enzyme Inhibition and Medicinal Chemistry. 2016 ; Vol. 31, No. 6. pp. 1286-1299.
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