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Literature DB >> 15050639

Modified norcantharidins; synthesis, protein phosphatases 1 and 2A inhibition, and anticancer activity.

Matthew E Hart¹, A Richard Chamberlin, Cecilia Walkom, Jennette A Sakoff, Adam McCluskey.

Abstract

Fourteen modified norcantharidin analogues have been synthesised and screened for their ability to inhibit the serine/threonine protein phosphatases 1 and 2A. The most potent compounds found were 10 (PP1 IC(50)=13+/-5 microM; PP2A IC(50)=7+/-3 microM) and 16 (PP1 IC(50)=18+/-8 microM; PP2A IC(50)=3.2+/-0.4 microM). Overall, only analogues possessing at least one acidic residue at the former anhydride warhead displayed any PP1 or PP2A inhibitory action. The ability of these analogues to inhibit PP1 and PP2A correlates well with their observed anti-cancer activity against a panel of five cancer cell lines: A2780 (human ovarian carcinoma), G401 (human kidney carcinoma), HT29 (human colorectal carcinoma), H460 (human lung carcinoma) and L1210 (murine leukemia).

Entities: Chemical Disease Gene Species

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Year: 2004 PMID： 15050639 DOI： 10.1016/j.bmcl.2004.01.093

Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823

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Cited

15 in total

1. Synthesis of a norcantharidin-tethered guanosine: Protein phosphatase-1 inhibitors that change alternative splicing.

Authors: Stefan Kwiatkowski; Vitaliy M Sviripa; Zhaiyi Zhang; Alison E Wendlandt; Claudia Höbartner; David S Watt; Stefan Stamm
Journal: Bioorg Med Chem Lett Date: 2015-12-18 Impact factor: 2.823

2. Inhibition of serine/threonine phosphatase PP2A enhances cancer chemotherapy by blocking DNA damage induced defense mechanisms.

Authors: Jie Lu; John S Kovach; Francis Johnson; Jeffrey Chiang; Richard Hodes; Russell Lonser; Zhengping Zhuang
Journal: Proc Natl Acad Sci U S A Date: 2009-06-29 Impact factor: 11.205

3. Effect of norcantharidin on proliferation and invasion of human gallbladder carcinoma GBC-SD cells.

Authors: Yue-Zu Fan; Jin-Ye Fu; Ze-Ming Zhao; Cun-Qiu Chen
Journal: World J Gastroenterol Date: 2005-04-28 Impact factor: 5.742

4. Synthesis and characterization of pseudocantharidins, novel phosphatase modulators that promote the inclusion of exon 7 into the SMN (survival of motoneuron) pre-mRNA.

Authors: Zhaiyi Zhang; Olga Kelemen; Maria A van Santen; Sharon M Yelton; Alison E Wendlandt; Vitaliy M Sviripa; Mathieu Bollen; Monique Beullens; Henning Urlaub; Reinhard Lührmann; David S Watt; Stefan Stamm
Journal: J Biol Chem Date: 2011-01-10 Impact factor: 5.157

5. Enhancing Therapeutic Efficacy of Cisplatin by Blocking DNA Damage Repair.

Authors: Yuwei Cong; Liangyan Wang; Zigui Wang; Shasha He; Dongfang Zhou; Xiabin Jing; Yubin Huang
Journal: ACS Med Chem Lett Date: 2016-08-24 Impact factor: 4.345

6. Crystal structures of protein phosphatase-1 bound to nodularin-R and tautomycin: a novel scaffold for structure-based drug design of serine/threonine phosphatase inhibitors.

Authors: Matthew S Kelker; Rebecca Page; Wolfgang Peti
Journal: J Mol Biol Date: 2008-11-01 Impact factor: 5.469

7. Crystal structures and mutagenesis of PPP-family ser/thr protein phosphatases elucidate the selectivity of cantharidin and novel norcantharidin-based inhibitors of PP5C.

Authors: Debasish Chattopadhyay; Mark R Swingle; Edward A Salter; Eric Wood; Brandon D'Arcy; Catherine Zivanov; Kevin Abney; Alla Musiyenko; Scott F Rusin; Arminja Kettenbach; Larry Yet; Chad E Schroeder; Jennifer E Golden; Wade H Dunham; Anne-Claude Gingras; Surajit Banerjee; David Forbes; Andrzej Wierzbicki; Richard E Honkanen
Journal: Biochem Pharmacol Date: 2016-03-23 Impact factor: 5.858