Literature DB >> 22480849

Structural modifications modulate stability of glutathione-activated arylated diazeniumdiolate prodrugs.

Rahul S Nandurdikar1, Anna E Maciag, Ryan J Holland, Zhao Cao, Paul J Shami, Lucy M Anderson, Larry K Keefer, Joseph E Saavedra.   

Abstract

JS-K, a diazeniumdiolate-based nitric oxide (NO)-releasing prodrug, is currently in late pre-clinical development as an anti-cancer drug candidate. This prodrug was designed to be activated by glutathione (GSH) to release NO. To increase the potency of JS-K, we are investigating the effect of slowing the reaction of the prodrugs with GSH. Herein, we report the effect of replacement of nitro group(s) by other electron-withdrawing group(s) in JS-K and its homo-piperazine analogues on GSH activation and the drugs' biological activity. We show that nitro-to-cyano substitution increases the half-life of the prodrug in the presence of GSH without compromising the compound's in vivo antitumor activity.
Copyright © 2012 Elsevier Ltd. All rights reserved.

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Year:  2012        PMID： 22480849      PMCID： PMC3590845          DOI： 10.1016/j.bmc.2012.02.045

Source DB:  PubMed          Journal:  Bioorg Med Chem        ISSN： 0968-0896            Impact factor:   3.641


  7 in total

1.  Activation of the c-Jun N-terminal kinase/activating transcription factor 3 (ATF3) pathway characterizes effective arylated diazeniumdiolate-based nitric oxide-releasing anticancer prodrugs.

Authors:  Anna E Maciag; Rahul S Nandurdikar; Sam Y Hong; Harinath Chakrapani; Bhalchandra Diwan; Nicole L Morris; Paul J Shami; Yih-Horng Shiao; Lucy M Anderson; Larry K Keefer; Joseph E Saavedra
Journal:  J Med Chem       Date:  2011-10-28       Impact factor: 7.446

2.  Antitumor activity of JS-K [O2-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate] and related O2-aryl diazeniumdiolates in vitro and in vivo.

Authors:  Paul J Shami; Joseph E Saavedra; Challice L Bonifant; Jingxi Chu; Vidya Udupi; Swati Malaviya; Brian I Carr; Siddhartha Kar; Meifeng Wang; Lee Jia; Xinhua Ji; Larry K Keefer
Journal:  J Med Chem       Date:  2006-07-13       Impact factor: 7.446

3.  JS-K, a glutathione/glutathione S-transferase-activated nitric oxide donor of the diazeniumdiolate class with potent antineoplastic activity.

Authors:  Paul J Shami; Joseph E Saavedra; Lai Y Wang; Challice L Bonifant; Bhalchandra A Diwan; Shivendra V Singh; Yijun Gu; Stephen D Fox; Gregory S Buzard; Michael L Citro; David J Waterhouse; Keith M Davies; Xinhua Ji; Larry K Keefer
Journal:  Mol Cancer Ther       Date:  2003-04       Impact factor: 6.261

4.  JS-K, a GST-activated nitric oxide generator, induces DNA double-strand breaks, activates DNA damage response pathways, and induces apoptosis in vitro and in vivo in human multiple myeloma cells.

Authors:  Tanyel Kiziltepe; Teru Hideshima; Kenji Ishitsuka; Enrique M Ocio; Noopur Raje; Laurence Catley; Chun-Qi Li; Laura J Trudel; Hiroshi Yasui; Sonia Vallet; Jeffery L Kutok; Dharminder Chauhan; Constantine S Mitsiades; Joseph E Saavedra; Gerald N Wogan; Larry K Keefer; Paul J Shami; Kenneth C Anderson
Journal:  Blood       Date:  2007-03-23       Impact factor: 22.113

5.  The nitric oxide prodrug JS-K is effective against non-small-cell lung cancer cells in vitro and in vivo: involvement of reactive oxygen species.

Authors:  Anna E Maciag; Harinath Chakrapani; Joseph E Saavedra; Nicole L Morris; Ryan J Holland; Ken M Kosak; Paul J Shami; Lucy M Anderson; Larry K Keefer
Journal:  J Pharmacol Exp Ther       Date:  2010-10-20       Impact factor: 4.030

6.  Synthesis, mechanistic studies, and anti-proliferative activity of glutathione/glutathione S-transferase-activated nitric oxide prodrugs.

Authors:  Harinath Chakrapani; Ravi C Kalathur; Anna E Maciag; Michael L Citro; Xinhua Ji; Larry K Keefer; Joseph E Saavedra
Journal:  Bioorg Med Chem       Date:  2008-09-30       Impact factor: 3.641

7.  Synthesis and evaluation of piperazine and homopiperazine analogues of JS-K, an anti-cancer lead compound.

Authors:  Rahul S Nandurdikar; Anna E Maciag; Michael L Citro; Paul J Shami; Larry K Keefer; Joseph E Saavedra; Harinath Chakrapani
Journal:  Bioorg Med Chem Lett       Date:  2009-03-28       Impact factor: 2.823
  7 in total
  4 in total

1.  Chemical Reactivity Window Determines Prodrug Efficiency toward Glutathione Transferase Overexpressing Cancer Cells.

Authors:  Marike W van Gisbergen; Marcus Cebula; Jie Zhang; Astrid Ottosson-Wadlund; Ludwig Dubois; Philippe Lambin; Kenneth D Tew; Danyelle M Townsend; Guido R M M Haenen; Marie-José Drittij-Reijnders; Hisao Saneyoshi; Mika Araki; Yuko Shishido; Yoshihiro Ito; Elias S J Arnér; Hiroshi Abe; Ralf Morgenstern; Katarina Johansson
Journal:  Mol Pharm       Date:  2016-04-28       Impact factor: 4.939

2.  Nitric oxide-releasing prodrug triggers cancer cell death through deregulation of cellular redox balance.

Authors:  Anna E Maciag; Ryan J Holland; Y-S Robert Cheng; Luis G Rodriguez; Joseph E Saavedra; Lucy M Anderson; Larry K Keefer
Journal:  Redox Biol       Date:  2013-02-01       Impact factor: 11.799

3.  JS-K induces reactive oxygen species-dependent anti-cancer effects by targeting mitochondria respiratory chain complexes in gastric cancer.

Authors:  Xudong Zhao; Aizhen Cai; Zheng Peng; Wenquan Liang; Hongqing Xi; Peiyu Li; Guozhu Chen; Jiyun Yu; Lin Chen
Journal:  J Cell Mol Med       Date:  2019-01-22       Impact factor: 5.310

4.  Nitric oxide (NO) releasing poly ADP-ribose polymerase 1 (PARP-1) inhibitors targeted to glutathione S-transferase P1-overexpressing cancer cells.

Authors:  Anna E Maciag; Ryan J Holland; Youseung Kim; Vandana Kumari; Christina E Luthers; Waheed S Sehareen; Debanjan Biswas; Nicole L Morris; Xinhua Ji; Lucy M Anderson; Joseph E Saavedra; Larry K Keefer
Journal:  J Med Chem       Date:  2014-02-25       Impact factor: 7.446
  4 in total

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