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Molecules 2015, 20(1), 1031-1045;

Synthesis and in Vitro Screening of Phenylbipyridinylpyrazole Derivatives as Potential Antiproliferative Agents

Chemical Kinomics Research Center, Korea Institute of Science and Technology, Hwarangno 14-gil 5, Seongbuk-gu, Seoul 136-791, Korea
Department of Biological Chemistry, Korea University of Science and Technology, 113 Gwahangno, Yuseong-gu, Daejeon 305-333, Korea
College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, Korea
Department of Chemistry, Kwangwoon University, Seoul 139-701, Korea
These authors contributed equally to this work.
Author to whom correspondence should be addressed.
Academic Editor: Derek J. McPhee
Received: 10 December 2014 / Accepted: 4 January 2015 / Published: 9 January 2015
(This article belongs to the Section Medicinal Chemistry)
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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 5aj 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 GI50 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 5aj are promising therapeutic agents for targeting different human malignancies. Prediction of drug-likeness and toxicity of these newly synthesized derivatives were also considered. View Full-Text
Keywords: cancer; cell lines; phenylbipyridinylpyrazole; antiproliferative agents; COMPARE analysis cancer; cell lines; phenylbipyridinylpyrazole; antiproliferative agents; COMPARE analysis

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Al-Sanea, M.M.; Elkamhawy, A.; Zakaria, A.; Park, B.S.; Kwon, Y.; Lee, S.H.; Lee, S.W.; Kim, I.T. Synthesis and in Vitro Screening of Phenylbipyridinylpyrazole Derivatives as Potential Antiproliferative Agents. Molecules 2015, 20, 1031-1045.

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