Antimitotic sulfonamides inhibit microtubule assembly dynamics and cancer cell proliferation

Biochemistry
Renu MohanD Panda

Abstract

Several sulfonamides have antitumor activities and are currently undergoing clinical evaluation for the treatment of cancer. In this study, we have elucidated the antiproliferative mechanism of action of five indole sulfonamides. The indole sulfonamides inhibited the polymerization of microtubule protein into microtubules in vitro. In addition, three representative derivatives, ER-68378 (2), ER-68384 (4) and ER-68394 (5), suppressed the dynamic instability behavior at the plus ends of individual steady-state microtubules in vitro. The analogues inhibited HeLa cell proliferation with half-maximal inhibitory concentrations in the range of 6-17 microM. The compounds blocked cell cycle progression at mitosis. At their lowest effective antimitotic concentrations, they depolymerized the spindle microtubules and disorganized the chromosomes but did not affect the microtubules in interphase cells. However, at relatively high concentrations, interphase microtubules were also depolymerized by these sulfonamides. Furthermore, all five compounds were found to induce apoptosis in the cells in association with the phosphorylation of bcl-2. The results suggest that the indole sulfonamides inhibit cell proliferation at mitosis by perturbing th...Continue Reading

References

Jul 4, 1990·Journal of the National Cancer Institute·P SkehanM R Boyd
Mar 1, 1996·Medicinal Research Reviews·E Hamel
Feb 3, 1998·Molecular and Cellular Biology·J S Lanni, T Jacks
Nov 7, 1998·The Journal of Biological Chemistry·C D ScatenaJ A Pietenpol
Feb 16, 1999·Cell·E NogalesK H Downing
Oct 26, 2001·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Y OzawaK Yoshimatsu
Jul 30, 2002·Proceedings of the National Academy of Sciences of the United States of America·Paraskevi GiannakakouTito Fojo
Aug 29, 2003·Journal of Enzyme Inhibition and Medicinal Chemistry·G LacondeJ P Hénichart
Apr 2, 2004·Nature Reviews. Cancer·Mary Ann Jordan, Leslie Wilson
Apr 20, 2005·Bioorganic & Medicinal Chemistry Letters·Clinton M YeungDale J Kempf

❮ Previous
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Citations

Jan 24, 2014·Acta Crystallographica. Section E, Structure Reports Online·Parameshwar Adimoole SuchetanSwamy Sreenivasa
Dec 22, 2015·The Journal of Organic Chemistry·Wucheng XieBaiquan Wang
Nov 28, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Zhixu ZhouTiemin Sun
Feb 7, 2013·Journal of Inorganic Biochemistry·José Luis García-GiménezGloria Alzuet Piña
Nov 29, 2011·European Journal of Medicinal Chemistry·Sally S El-NakkadyIman A Y Ghannam
Sep 3, 2011·Bioorganic & Medicinal Chemistry Letters·Lu-Yun ZhangShu-Fan Yin
Apr 27, 2007·Clinical Oncology : a Journal of the Royal College of Radiologists·D M Patterson, G J S Rustin
Apr 28, 2007·Medicinal Research Reviews·Bhabatarak BhattacharyyaMithu Banerjee
Apr 4, 2008·IUBMB Life·Parminder SinghDulal Panda
Oct 25, 2013·Cell Biology International·Raziye MohammadpourNader Sheinabi
Mar 13, 2014·Chemistry : a European Journal·Changduo PanChengjian Zhu
Jul 10, 2010·Bioorganic & Medicinal Chemistry·Aitziber A SagardoyVictor Martinez-Merino
May 14, 2016·Organic & Biomolecular Chemistry·Zengqiang Song, Andrey P Antonchick
May 22, 2016·BMC Biochemistry·Yasunori FukudaJunji Matsui
Nov 5, 2016·The Journal of Organic Chemistry·Lanting XuDawei Ma
Jan 31, 2017·Biochemical and Biophysical Research Communications·Yasunori FukudaYuji Kawamata
Jul 4, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Malose J MphahleleYee Siew Choong
Oct 27, 2018·Medicinal Research Reviews·Alba Vicente-BlázquezRafael Peláez
Jan 10, 2018·Organic & Biomolecular Chemistry·Changduo PanJin-Tao Yu
May 23, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Katyayani TatipartiArun K Iyer
Jun 17, 2020·Cancer Cell International·Zhi-Gang SunNan Zhang
Oct 1, 2019·The Journal of Organic Chemistry·Mohit KumarDipankar Koley
Dec 6, 2018·Journal of Chemical Information and Modeling·Sarmistha MajumdarShubhra Ghosh Dastidar

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