N-Sulfonyl-aminobiaryls as Antitubulin Agents and Inhibitors of Signal Transducers and Activators of Transcription 3 (STAT3) Signaling

Mei-Jung Lai; Hsueh Yun Lee; Hsun-Yueh Chuang; Li-Hsun Chang; An-Chi Tsai; Mei Chuan Chen; Han-Lin Huang; Yi-Wen Wu; Che-Ming Teng; Shiow Lin Pan; Yi-Min Liu; Samir Mehndiratta; Jing Ping Liou

doi:10.1021/acs.jmedchem.5b00659

N-Sulfonyl-aminobiaryls as Antitubulin Agents and Inhibitors of Signal Transducers and Activators of Transcription 3 (STAT3) Signaling

Mei-Jung Lai, Hsueh Yun Lee, Hsun-Yueh Chuang, Li-Hsun Chang, An-Chi Tsai, Mei Chuan Chen, Han-Lin Huang, Yi-Wen Wu, Che-Ming Teng, Shiow Lin Pan, Yi-Min Liu, Samir Mehndiratta, Jing Ping Liou

Research output: Contribution to journal › Article › peer-review

25 Citations (Scopus)

Abstract

A series of N-sulfonyl-aminobiaryl derivatives have been examined as novel antitubulin agents. Compound 21 [N-(4′-cyano-3′-fluoro-biphenyl-2-yl)-4-methoxy-benzenesulfonamide] exhibits remarkable antiproliferative activity against four cancer cell lines (pancreatic AsPC-1, lung A549, liver Hep3B, and prostate PC-3) with a mean GI₅₀ value of 57.5 nM. Additional assays reveal that 21 inhibits not only tubulin polymerization but also the phosphorylation of STAT3 inhibition with an IC₅₀ value of 0.2 μM. Four additional compounds (8, 10, 19, and 35) are also able to inhibit this phosphorylation. This study describes novel N-sulfonyl-aminobiaryl (biaryl-benzenesulfonamides) as potent anticancer agents targeting both STAT3 and tubulin. (Chemical Equation Presented).

Original language	English
Pages (from-to)	6549-6558
Number of pages	10
Journal	Journal of Medicinal Chemistry
Volume	58
Issue number	16
DOIs	https://doi.org/10.1021/acs.jmedchem.5b00659
Publication status	Published - Aug 27 2015

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1021/acs.jmedchem.5b00659

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Lai, M-J., Lee, H. Y., Chuang, H-Y., Chang, L-H., Tsai, A-C., Chen, M. C., Huang, H-L., Wu, Y-W., Teng, C-M., Pan, S. L., Liu, Y-M., Mehndiratta, S., & Liou, J. P. (2015). N-Sulfonyl-aminobiaryls as Antitubulin Agents and Inhibitors of Signal Transducers and Activators of Transcription 3 (STAT3) Signaling. Journal of Medicinal Chemistry, 58(16), 6549-6558. https://doi.org/10.1021/acs.jmedchem.5b00659

Lai, M-J , Lee, HY, Chuang, H-Y, Chang, L-H, Tsai, A-C, Chen, MC , Huang, H-L, Wu, Y-W, Teng, C-M, Pan, SL , Liu, Y-M, Mehndiratta, S & Liou, JP 2015, 'N-Sulfonyl-aminobiaryls as Antitubulin Agents and Inhibitors of Signal Transducers and Activators of Transcription 3 (STAT3) Signaling', Journal of Medicinal Chemistry, vol. 58, no. 16, pp. 6549-6558. https://doi.org/10.1021/acs.jmedchem.5b00659

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abstract = "A series of N-sulfonyl-aminobiaryl derivatives have been examined as novel antitubulin agents. Compound 21 [N-(4′-cyano-3′-fluoro-biphenyl-2-yl)-4-methoxy-benzenesulfonamide] exhibits remarkable antiproliferative activity against four cancer cell lines (pancreatic AsPC-1, lung A549, liver Hep3B, and prostate PC-3) with a mean GI50 value of 57.5 nM. Additional assays reveal that 21 inhibits not only tubulin polymerization but also the phosphorylation of STAT3 inhibition with an IC50 value of 0.2 μM. Four additional compounds (8, 10, 19, and 35) are also able to inhibit this phosphorylation. This study describes novel N-sulfonyl-aminobiaryl (biaryl-benzenesulfonamides) as potent anticancer agents targeting both STAT3 and tubulin. (Chemical Equation Presented).",

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AU - Chuang, Hsun-Yueh

AU - Chang, Li-Hsun

AU - Tsai, An-Chi

AU - Chen, Mei Chuan

AU - Huang, Han-Lin

AU - Wu, Yi-Wen

AU - Teng, Che-Ming

AU - Pan, Shiow Lin

AU - Liu, Yi-Min

AU - Mehndiratta, Samir

AU - Liou, Jing Ping

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N2 - A series of N-sulfonyl-aminobiaryl derivatives have been examined as novel antitubulin agents. Compound 21 [N-(4′-cyano-3′-fluoro-biphenyl-2-yl)-4-methoxy-benzenesulfonamide] exhibits remarkable antiproliferative activity against four cancer cell lines (pancreatic AsPC-1, lung A549, liver Hep3B, and prostate PC-3) with a mean GI50 value of 57.5 nM. Additional assays reveal that 21 inhibits not only tubulin polymerization but also the phosphorylation of STAT3 inhibition with an IC50 value of 0.2 μM. Four additional compounds (8, 10, 19, and 35) are also able to inhibit this phosphorylation. This study describes novel N-sulfonyl-aminobiaryl (biaryl-benzenesulfonamides) as potent anticancer agents targeting both STAT3 and tubulin. (Chemical Equation Presented).

AB - A series of N-sulfonyl-aminobiaryl derivatives have been examined as novel antitubulin agents. Compound 21 [N-(4′-cyano-3′-fluoro-biphenyl-2-yl)-4-methoxy-benzenesulfonamide] exhibits remarkable antiproliferative activity against four cancer cell lines (pancreatic AsPC-1, lung A549, liver Hep3B, and prostate PC-3) with a mean GI50 value of 57.5 nM. Additional assays reveal that 21 inhibits not only tubulin polymerization but also the phosphorylation of STAT3 inhibition with an IC50 value of 0.2 μM. Four additional compounds (8, 10, 19, and 35) are also able to inhibit this phosphorylation. This study describes novel N-sulfonyl-aminobiaryl (biaryl-benzenesulfonamides) as potent anticancer agents targeting both STAT3 and tubulin. (Chemical Equation Presented).

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N-Sulfonyl-aminobiaryls as Antitubulin Agents and Inhibitors of Signal Transducers and Activators of Transcription 3 (STAT3) Signaling

Abstract

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