Synthesis and in vitro screening of phenylbipyridinylpyrazole derivatives as potential antiproliferative agents

Mohammad M. Al -Sanea, Ahmed Elkamhawy, Ahmed Zakaria, Byung Sun Park, Youngjoo Kwon, So Ha Lee, Sang Woo Lee, In Tae Kim

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17 Scopus citations


A series of phenylbipyridinylpyrazoles was synthesized through the reaction of 2-(4-(2-chloropyridin-4-yl)-3-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl)acetonitrile (4) with different 6-substituted pyridine-3-ylboronic acids. The final compounds 5a-j were screened at 10 μM against over 60 tumor cell lines at the U.S. National Cancer Institute (NCI). In light of the NCI results, compounds 5c and 5h showed a broad spectrum of activity against NCI cell lines with mean growth of 53% and 58%, respectively. Compound 5e behaved differently as it showed high degree of selectivity and potency by inhibiting 96% of growth of leukemia SR cell line at 10 μM. Standard COMPARE analyses were performed at the GI 50 level and the results exhibit high correlation in the form of pairwise correlation coefficient (PCC) of more than 0.6 between three of the current compounds and three standard known anticancer agents. Compound 5e demonstrated high correlation levels with merbarone (NSC S336628) with a PCC value of 0.631. Compound 5h showed a considerably high PCC value of 0.626 with dichloroallyl lawsone, while compound 5i, showed PCC values of 0.601 and 0.604 with both dichloroallyl lawsone and N,N-dibenzyldaunomycin (NSC S268242), respectively. These three standard agents have anticancer activity via two major mechanism of actions, inhibition of topoisomerase II and inhibition of biosynthesis of pyrimidine nucleotides, therefore, compounds 5a-j are promising therapeutic agents for targeting different human malignancies. Prediction of drug-likeness and toxicity of these newly synthesized derivatives were also considered.

Original languageEnglish
Pages (from-to)1031-1045
Number of pages15
Issue number1
StatePublished - 1 Jan 2015

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© 2015 by the authors licensee MDPI Basel Switzerland.


  • Antiproliferative agents
  • COMPARE analysis
  • Cancer
  • Cell lines
  • Phenylbipyridinylpyrazole


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