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Our Science – Saavedra Website

Joseph E. Saavedra, Ph.D.

Selected Publications

1)  Kaczmarek MZ, Holland RJ, Lavanier SA, Troxler JA, Fesenkova VI, Hanson CA, Cmarik JL, Saavedra JE, Keefer LK, Ruscetti SK.
Mechanism of action for the cytotoxic effects of the nitric oxide prodrug JS-K in murine erythroleukemia cells.
Leuk. Res. 38: 377-82, 2014.
2)  Maciag AE, Holland RJ, Kim Y, Kumari V, Luthers CE, Sehareen WS, Biswas D, Morris NL, Ji X, Anderson LM, Saavedra JE, Keefer LK.
Nitric Oxide (NO) Releasing Poly ADP-ribose Polymerase 1 (PARP-1) Inhibitors Targeted to Glutathione S-Transferase P1-Overexpressing Cancer Cells.
J. Med. Chem. 2014.
3)  Weidensteiner C, Reichardt W, Shami PJ, Saavedra JE, Keefer LK, Baumer B, Werres A, Jasinski R, Osterberg N, Weyerbrock A.
Effects of the nitric oxide donor JS-K on the blood-tumor barrier and on orthotopic U87 rat gliomas assessed by MRI.
Nitric Oxide. 30: 17-25, 2013.
4)  Holland RJ, Paulisch R, Cao Z, Keefer LK, Saavedra JE, Donzelli S.
Enzymatic generation of the NO/HNO-releasing IPA/NO anion at controlled rates in physiological media using ß-galactosidase.
Nitric Oxide. 35: 131-6, 2013.
5)  Maciag AE, Holland RJ, Robert Cheng YS, Rodriguez LG, Saavedra JE, Anderson LM, Keefer LK.
Nitric oxide-releasing prodrug triggers cancer cell death through deregulation of cellular redox balance.
Redox Biol. 1: 115-24, 2013.
6)  Carpenter AW, Reighard KP, Saavedra JE, Schoenfisch MH.
O (2)-Protected Diazeniumdiolate-Modified Silica Nanoparticles for Extended Nitric Oxide Release from Dental Composites.
Biomater Sci. 1: 456-459, 2013.
7)  Holland RJ, Maciag AE, Kumar V, Shi L, Saavedra JE, Prud'homme RK, Chakrapani H, Keefer LK.
Cross-linking protein glutathionylation mediated by O2-arylated bis-diazeniumdiolate "Double JS-K".
Chem. Res. Toxicol. 25: 2670-7, 2012.
8)  Nandurdikar RS, Maciag AE, Cao Z, Keefer LK, Saavedra JE.
Diazeniumdiolated carbamates: a novel class of nitric oxide donors.
Bioorg. Med. Chem. 20: 2025-9, 2012.
9)  Kogias E, Osterberg N, Baumer B, Psarras N, Koentges C, Papazoglou A, Saavedra JE, Keefer LK, Weyerbrock A.
Growth-inhibitory and chemosensitizing effects of the glutathione-S-transferase-p-activated nitric oxide donor PABA/NO in malignant gliomas.
Int. J. Cancer. 130: 1184-94, 2012.
10)  Weyerbrock A, Osterberg N, Psarras N, Baumer B, Kogias E, Werres A, Bette S, Saavedra JE, Keefer LK, Papazoglou A.
JS-K, a glutathione S-transferase-activated nitric oxide donor with antineoplastic activity in malignant gliomas.
Neurosurgery. 70: 497-510; discussion 510, 2012.
11)  Biswas D, Cao Z, Keefer LK, Saavedra JE.
Nitrous oxide as a primary product in base-mediated ß-elimination reactions of diazeniumdiolated benzylamine derivatives.
Chem. Commun. (Camb.). 48: 5931-3, 2012.
12)  Biswas D, Holland RJ, Deschamps JR, Cao Z, Keefer LK, Saavedra JE.
O2-functionalized methylamine diazeniumdiolates: evidence for E ? Z equilibration in an acyclic system.
J. Org. Chem. 77: 10804-10, 2012.
13)  Nandurdikar RS, Maciag AE, Holland RJ, Cao Z, Shami PJ, Anderson LM, Keefer LK, Saavedra JE.
Structural modifications modulate stability of glutathione-activated arylated diazeniumdiolate prodrugs.
Bioorg. Med. Chem. 20: 3094-9, 2012.
14)  Maciag AE, Holland RJ, Saavedra JE, Chakrapani H, Shami PJ, Keefer LK.
Thiol Modification By Pharmacologically Active Agents of the Diazeniumdiolate Class.
For Immunopathol Dis Therap. 3: 91-95, 2012.
15)  Weyerbrock A, Walbridge S, Saavedra JE, Keefer LK, Oldfield EH.
Differential effects of nitric oxide on blood-brain barrier integrity and cerebral blood flow in intracerebral C6 gliomas.
Neuro-oncology. 13: 203-11, 2011.
16)  Hogg ME, Varu VN, Vavra AK, Popowich DA, Banerjee MN, Martinez J, Jiang Q, Saavedra JE, Keefer LK, Kibbe MR.
Effect of nitric oxide on neointimal hyperplasia based on sex and hormone status.
Free Radic. Biol. Med. 50: 1065-74, 2011.
17)  Salmon DJ, Torres de Holding CL, Thomas L, Peterson KV, Goodman GP, Saavedra JE, Srinivasan A, Davies KM, Keefer LK, Miranda KM.
HNO and NO release from a primary amine-based diazeniumdiolate as a function of pH.
Inorg Chem. 50: 3262-70, 2011.
18)  McMurtry V, Saavedra JE, Nieves-Alicea R, Simeone AM, Keefer LK, Tari AM.
JS-K, a nitric oxide-releasing prodrug, induces breast cancer cell death while sparing normal mammary epithelial cells.
Int. J. Oncol. 38: 963-71, 2011.
19)  Qu W, Cheng L, Dill AL, Saavedra JE, Hong SY, Keefer LK, Waalkes MP.
Nitric oxide donor, V-PROLI/NO, provides protection against arsenical induced toxicity in rat liver cells: requirement for Cyp1a1.
Chem. Biol. Interact. 193: 88-96, 2011.
20)  Nandurdikar RS, Keefer LK, Saavedra JE.
Novel protection-deprotection strategies in diazeniumdiolate chemistry: synthesis of V-IPA/NO.
Chem. Commun. (Camb.). 47: 6710-2, 2011.
21)  Maciag AE, Chakrapani H, Saavedra JE, Morris NL, Holland RJ, Kosak KM, Shami PJ, Anderson LM, Keefer LK.
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.
J. Pharmacol. Exp. Ther. 336: 313-20, 2011.
22)  Oladeinde OA, Hong SY, Holland RJ, Maciag AE, Keefer LK, Saavedra JE, Nandurdikar RS.
"Click" reaction in conjunction with diazeniumdiolate chemistry: developing high-load nitric oxide donors.
Org. Lett. 12: 4256-9, 2010.
23)  Andrei D, Salmon DJ, Donzelli S, Wahab A, Klose JR, Citro ML, Saavedra JE, Wink DA, Miranda KM, Keefer LK.
Dual mechanisms of HNO generation by a nitroxyl prodrug of the diazeniumdiolate (NONOate) class.
J. Am. Chem. Soc. 132: 16526-32, 2010.
24)  Nandurdikar RS, Maciag AE, Hong SY, Chakrapani H, Citro ML, Keefer LK, Saavedra JE.
Glycosylated PROLI/NO derivatives as nitric oxide prodrugs.
Org. Lett. 12: 56-9, 2010.
25)  Varu VN, Ahanchi SS, Hogg ME, Bhikhapurwala HA, Chen A, Popowich DA, Vavra AK, Martinez J, Jiang Q, Saavedra JE, Hrabie JA, Keefer LK, Kibbe MR.
Insulin enhances the effect of nitric oxide at inhibiting neointimal hyperplasia in a rat model of type 1 diabetes.
Am. J. Physiol. Heart Circ. Physiol. 299: H772-9, 2010.
26)  Tsihlis ND, Murar J, Kapadia MR, Ahanchi SS, Oustwani CS, Saavedra JE, Keefer LK, Kibbe MR.
Isopropylamine NONOate (IPA/NO) moderates neointimal hyperplasia following vascular injury.
J. Vasc. Surg. 51: 1248-59, 2010.
27)  Kiziltepe T, Anderson KC, Kutok JL, Jia L, Boucher KM, Saavedra JE, Keefer LK, Shami PJ.
JS-K has potent anti-angiogenic activity in vitro and inhibits tumour angiogenesis in a multiple myeloma model in vivo.
J. Pharm. Pharmacol. 62: 145-51, 2010.
28)  Nath N, Chattopadhyay M, Pospishil L, Cieciura LZ, Goswami S, Kodela R, Saavedra JE, Keefer LK, Kashfi K.
JS-K, a nitric oxide-releasing prodrug, modulates ß-catenin/TCF signaling in leukemic Jurkat cells: evidence of an S-nitrosylated mechanism.
Biochem. Pharmacol. 80: 1641-9, 2010.
29)  Kumar V, Hong SY, Maciag AE, Saavedra JE, Adamson DH, Prud'homme RK, Keefer LK, Chakrapani H.
Stabilization of the nitric oxide (NO) prodrugs and anticancer leads, PABA/NO and Double JS-K, through incorporation into PEG-protected nanoparticles.
Mol. Pharm. 7: 291-8, 2010.
30)  Reynolds MM, Saavedra JE, Showalter BM, Valdez CA, Shanklin AP, Oh BK, Keefer LK, Meyerhoff ME.
Tailored Synthesis of Nitric Oxide-Releasing Polyurethanes Using O-Protected Diazeniumdiolated Chain Extenders.
J Mater Chem. 20: 3107-2114, 2010.
31)  Hong SY, Borchert GL, Maciag AE, Nandurdikar RS, Saavedra JE, Keefer LK, Phang JM, Chakrapani H.
The Nitric Oxide Prodrug V-PROLI/NO Inhibits Cellular Uptake of Proline.
ACS Med Chem Lett. 1: 386-389, 2010.
32)  Kiziltepe T, Hideshima T, Ishitsuka K, Ocio EM, Raje N, Catley L, Li CQ, Trudel LJ, Yasui H, Vallet S, Kutok JL, Chauhan D, Mitsiades CS, Saavedra JE, Wogan GN, Keefer LK, Shami PJ, Anderson KC.
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.
Blood. 110: 709-18, 2007.
33)  Chakrapani H, Showalter BM, Citro ML, Keefer LK, Saavedra JE.
Nitric oxide prodrugs: diazeniumdiolate anions of hindered secondary amines.
Org. Lett. 9: 4551-4, 2007.
34)  Qu W, Liu J, Fuquay R, Saavedra JE, Keefer LK, Waalkes MP.
The nitric oxide prodrug, V-PYRRO/NO, mitigates arsenic-induced liver cell toxicity and apoptosis.
Cancer Lett. 256: 238-45, 2007.
35)  Chakrapani H, Showalter BM, Kong L, Keefer LK, Saavedra JE.
V-PROLI/NO, a prodrug of the nitric oxide donor, PROLI/NO.
Org. Lett. 9: 3409-12, 2007.
36)  Townsend DM, Findlay VJ, Fazilev F, Ogle M, Fraser J, Saavedra JE, Ji X, Keefer LK, Tew KD.
A glutathione S-transferase pi-activated prodrug causes kinase activation concurrent with S-glutathionylation of proteins.
Mol. Pharmacol. 69: 501-8, 2006.
37)  Shami PJ, Saavedra JE, Bonifant CL, Chu J, Udupi V, Malaviya S, Carr BI, Kar S, Wang M, Jia L, Ji X, Keefer LK.
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.
J. Med. Chem. 49: 4356-66, 2006.
38)  Kong L, Saavedra JE, Buzard GS, Xu X, Hood BL, Conrads TP, Veenstra TD, Keefer LK.
Deamidation of peptides in aerobic nitric oxide solution by a nitrosative pathway.
Nitric Oxide. 14: 144-51, 2006.
39)  Waterhouse DJ, Saavedra JE, Davies KM, Citro ML, Xu X, Powell DA, Grimes GJ, Potti GK, Keefer LK.
Injectable formulation of disodium 1-[2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (PROLI/NO), an ultrafast nitric oxide donor prodrug.
Journal of pharmaceutical sciences. 95: 108-15, 2006.
40)  Udupi V, Yu M, Malaviya S, Saavedra JE, Shami PJ.
JS-K, a nitric oxide prodrug, induces cytochrome c release and caspase activation in HL-60 myeloid leukemia cells.
Leuk. Res. 30: 1279-83, 2006.
41)  Inami K, Nims RW, Srinivasan A, Citro ML, Saavedra JE, Cederbaum AI, Keefer LK.
Metabolism of a liver-selective nitric oxide-releasing agent, V-PYRRO/NO, by human microsomal cytochromes P450.
Nitric Oxide. 14: 309-15, 2006.
42)  Saavedra JE, Srinivasan A, Buzard GS, Davies KM, Waterhouse DJ, Inami K, Wilde TC, Citro ML, Cuellar M, Deschamps JR, Parrish D, Shami PJ, Findlay VJ, Townsend DM, Tew KD, Singh S, Jia L, Ji X, Keefer LK.
PABA/NO as an anticancer lead: analogue synthesis, structure revision, solution chemistry, reactivity toward glutathione, and in vitro activity.
J. Med. Chem. 49: 1157-64, 2006.
43)  Wang YN, Bohle DS, Bonifant CL, Chmurny GN, Collins JR, Davies KM, Deschamps J, Flippen-Anderson JL, Keefer LK, Klose JR, Saavedra JE, Waterhouse DJ, Ivanic J.
Chemistry of the diazeniumdiolates: Z right harpoon over left harpoon E isomerism.
J. Am. Chem. Soc. 127: 5388-95, 2005.
44)  Miranda KM, Katori T, Torres de Holding CL, Thomas L, Ridnour LA, McLendon WJ, Cologna SM, Dutton AS, Champion HC, Mancardi D, Tocchetti CG, Saavedra JE, Keefer LK, Houk KN, Fukuto JM, Kass DA, Paolocci N, Wink DA.
Comparison of the NO and HNO donating properties of diazeniumdiolates: primary amine adducts release HNO in Vivo.
J. Med. Chem. 48: 8220-8, 2005.
45)  Showalter BM, Reynolds MM, Valdez CA, Saavedra JE, Davies KM, Klose JR, Chmurny GN, Citro ML, Barchi JJ, Merz SI, Meyerhoff ME, Keefer LK.
Diazeniumdiolate ions as leaving groups in anomeric displacement reactions: a protection-deprotection strategy for ionic diazeniumdiolates.
J. Am. Chem. Soc. 127: 14188-9, 2005.
46)  Bohle DS, Ivanic J, Saavedra JE, Smith KN, Wang YN.
E/Z conformation and the vibrational spectroscopy of Me2NN(O)=NOMe.
The journal of physical chemistry. A. 109: 11317-21, 2005.
47)  Liu J, He YY, Chignell CF, Clark J, Myers P, Saavedra JE, Waalkes MP.
Limited protective role of V-PYRRO/NO against cholestasis produced by alpha-naphthylisothiocyanate in mice.
Biochem. Pharmacol. 70: 144-51, 2005.
48)  Xu X, Veenstra TD, Fox SD, Roman JM, Issaq HJ, Falk R, Saavedra JE, Keefer LK, Ziegler RG.
Measuring fifteen endogenous estrogens simultaneously in human urine by high-performance liquid chromatography-mass spectrometry.
Anal. Chem. 77: 6646-54, 2005.
49)  Qu W, Liu J, Fuquay R, Shimoda R, Sakurai T, Saavedra JE, Keefer LK, Waalkes MP.
The nitric oxide prodrug, V-PYRRO/NO, protects against cadmium toxicity and apoptosis at the cellular level.
Nitric Oxide. 12: 114-20, 2005.
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This page was last updated on 3/5/2014.