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Krishnamurthy Shyam

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Rui Zhu; Krishnamurthy Shyam; Raymond P Baumann; Kimiko Ishiguro; Eric Patridge; Philip G Penketh; Alan C Sartorelli
Chloroethylating and methylating dual function antineoplastic agents display superior cytotoxicity against repair proficient tumor cells.
Rui Zhu; Krishnamurthy Shyam; Raymond P Baumann; Philip G Penketh; Alan C Sartorelli
Hypoxia-selective O6-alkylguanine-DNA alkyltransferase inhibitors: design, synthesis, and evaluation of 6-(benzyloxy)-2-(aryldiazenyl)-9H-purines as prodrugs of O6-benzylguanine.
Rui Zhu; Helen A Seow; Krishnamurthy Shyam; Raymond P Baumann; Kimiko Ishiguro; Philip G Penketh; Alan C Sartorelli
Design of a hypoxia-activated prodrug inhibitor of O6-alkylguanine-DNA alkyltransferase.

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2013: Rui Zhu; Krishnamurthy Shyam; Raymond P Baumann; Kimiko Ishiguro; Eric Patridge; Philip G Penketh; Alan C Sartorelli
Chloroethylating and methylating dual function antineoplastic agents display superior cytotoxicity against repair proficient tumor cells.
Bioorganic & medicinal chemistry letters 2013;23(6):1853-9.
2013: Rui Zhu; Krishnamurthy Shyam; Raymond P Baumann; Philip G Penketh; Alan C Sartorelli
Hypoxia-selective O6-alkylguanine-DNA alkyltransferase inhibitors: design, synthesis, and evaluation of 6-(benzyloxy)-2-(aryldiazenyl)-9H-purines as prodrugs of O6-benzylguanine.
Journal of medicinal chemistry 2013;56(3):1355-9.
2012: Rui Zhu; Helen A Seow; Krishnamurthy Shyam; Raymond P Baumann; Kimiko Ishiguro; Philip G Penketh; Alan C Sartorelli
Design of a hypoxia-activated prodrug inhibitor of O6-alkylguanine-DNA alkyltransferase.
Bioorganic & medicinal chemistry letters 2012;22(19):6242-7.
2012: Eric V Patridge; Philip G Penketh; Raymond P Baumann; Emma S E Eriksson; Leif A Eriksson; Krishnamurthy Shyam; Rui Zhu; Alan C Sartorelli
7-Nitro-4-(phenylthio)benzofurazan is a potent generator of superoxide and hydrogen peroxide.
Archives of toxicology 2012;86(10):1613-25.
2012: Eugene Y Kim; Yanfeng Liu; Oluwatoyin M Akintujoye; Tina A Grove; Alan C Sartorelli; Krishnamurthy Shyam; Sara Rockwell
Preliminary studies with a new hypoxia-selective cytotoxin, KS119W, in vitro and in vivo.
Radiation research 2012;178(3):126-37.
2012: Philip G Penketh; Raymond P Baumann; Kimiko Ishiguro; Eric V Patridge; Krishnamurthy Shyam; Rui Zhu; Alan C Sartorelli
A strategy for selective O(6)-alkylguanine-DNA alkyltransferase depletion under hypoxic conditions.
Chemical biology & drug design 2012;80(2):279-90.
2012: Sara Rockwell; Helen A Seow; Krishnamurthy Shyam; Oluwatoyin M Akintujoye; Raymond P Baumann; Peter M Glazer; Kimiko Ishiguro; Yanfeng Liu; Philip G Penketh; Alan C Sartorelli
Preclinical evaluation of Laromustine for use in combination with radiation therapy in the treatment of solid tumors.
International journal of radiation biology 2012;88(3):277-85.
2011: Rui Zhu; Krishnamurthy Shyam; Raymond P Baumann; Mao-Chin Liu; Mei-Zhen Luo; Philip G Penketh; Alan C Sartorelli
4-nitrobenzyloxycarbonyl derivatives of O(6)-benzylguanine as hypoxia-activated prodrug inhibitors of O(6)-alkylguanine-DNA alkyltransferase (AGT), which produces resistance to agents targeting the O-6 position of DNA guanine.
Journal of medicinal chemistry 2011;54(21):7720-8.
2011: Philip G Penketh; Krishnamurthy Shyam; Hugh S Williamson; Rui Zhu; Raymond P Baumann; Emma S E Eriksson; Leif A Eriksson; Kimiko Ishiguro; Alan C Sartorelli
1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-[[1-(4-nitrophenyl)ethoxy]carbonyl]hydrazine (KS119): a cytotoxic prodrug with two stable conformations differing in biological and physical properties.
Chemical biology & drug design 2011;78(4):513-26.
2011: Raymond P Baumann; Kimiko Ishiguro; Philip G Penketh; Krishnamurthy Shyam; Rui Zhu; Alan C Sartorelli
KS900: A hypoxia-directed, reductively activated methylating antitumor prodrug that selectively ablates O(6)-alkylguanine-DNA alkyltransferase in neoplastic cells.
Biochemical pharmacology 2011;81(10):1201-10.
2010: Kimiko Ishiguro; Yong-Lian Zhu; Krishnamurthy Shyam; Philip G Penketh; Raymond P Baumann; Alan C Sartorelli
Quantitative relationship between guanine O(6)-alkyl lesions produced by Onrigin™ and tumor resistance by O(6)-alkylguanine-DNA alkyltransferase.
Biochemical pharmacology 2010;80(9):1317-25.
2010: Raymond P Baumann; Philip G Penketh; Kimiko Ishiguro; Krishnamurthy Shyam; Yong L Zhu; Alan C Sartorelli
Reductive activation of the prodrug 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-2-[[1-(4-nitrophenyl)ethoxy]carbonyl]hydrazine (KS119) selectively occurs in oxygen-deficient cells and overcomes O(6)-alkylguanine-DNA alkyltransferase mediated KS119 tumor cell resistance.
Biochemical pharmacology 2010;79(11):1553-61.
2008: Kimiko Ishiguro; Krishnamurthy Shyam; Philip G Penketh; Alan C Sartorelli
Development of an O(6)-alkylguanine-DNA alkyltransferase assay based on covalent transfer of the benzyl moiety from [benzene-3H]O(6)-benzylguanine to the protein.
Analytical biochemistry 2008;383(1):44-51.
2008: Raymond P Baumann; Philip G Penketh; Helen A Seow; Krishnamurthy Shyam; Alan C Sartorelli
Generation of oxygen deficiency in cell culture using a two-enzyme system to evaluate agents targeting hypoxic tumor cells.
Radiation research 2008;170(5):651-60.
2008: Philip G Penketh; Raymond P Baumann; Kimiko Ishiguro; Krishnamurthy Shyam; Helen A Seow; Alan C Sartorelli
Lethality to leukemia cell lines of DNA interstrand cross-links generated by Cloretazine derived alkylating species.
Leukemia research 2008;32(10):1546-53.
2006: Kimiko Ishiguro; Helen A Seow; Philip G Penketh; Krishnamurthy Shyam; Alan C Sartorelli
Mode of action of the chloroethylating and carbamoylating moieties of the prodrug cloretazine.
Molecular cancer therapeutics 2006;5(4):969-76.
2005: Kimiko Ishiguro; Krishnamurthy Shyam; Philip G Penketh; Alan C Sartorelli
Role of O6-alkylguanine-DNA alkyltransferase in the cytotoxic activity of cloretazine.
Molecular cancer therapeutics 2005;4(11):1755-63.
2005: Helen A Seow; Philip G Penketh; Krishnamurthy Shyam; Sara Rockwell; Alan C Sartorelli
1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-[[1-(4-nitrophenyl)ethoxy]carbonyl]hydrazine: an anticancer agent targeting hypoxic cells.
Proceedings of the National Academy of Sciences of the United States of America 2005;102(26):9282-7.
2005: Kevin P Rice; Philip G Penketh; Krishnamurthy Shyam; Alan C Sartorelli
Differential inhibition of cellular glutathione reductase activity by isocyanates generated from the antitumor prodrugs Cloretazine and BCNU.
Biochemical pharmacology 2005;69(10):1463-72.
2005: Raymond P Baumann; Helen A Seow; Krishnamurthy Shyam; Philip G Penketh; Alan C Sartorelli
The antineoplastic efficacy of the prodrug Cloretazine is produced by the synergistic interaction of carbamoylating and alkylating products of its activation.
Oncology research 2005;15(6):313-25.
2004: Philip G Penketh; Krishnamurthy Shyam; Raymond P Baumann; Joanna S Remack; Thomas P Brent; Alan C Sartorelli
1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-[(methylamino)carbonyl]hydrazine (VNP40101M): I. Direct inhibition of O6-alkylguanine-DNA alkyltransferase (AGT) by electrophilic species generated by decomposition.
Cancer chemotherapy and pharmacology 2004;53(4):279-87.
2004: Raymond P Baumann; Krishnamurthy Shyam; Philip G Penketh; Joanna S Remack; Thomas P Brent; Alan C Sartorelli
1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-[(methylamino)carbonyl]hydrazine (VNP40101M): II. Role of O6-alkylguanine-DNA alkyltransferase in cytotoxicity.
Cancer chemotherapy and pharmacology 2004;53(4):288-95.
2001: Philip G Penketh; William F Hodnick; Michael F Belcourt; Krishnamurthy Shyam; David H Sherman; Alan C Sartorelli
Inhibition of DNA cross-linking by mitomycin C by peroxidase-mediated oxidation of mitomycin C hydroquinone.
The Journal of biological chemistry 2001;276(37):34445-52.
2001: Rick A Finch; Krishnamurthy Shyam; Philip G Penketh; Alan C Sartorelli
1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-(methylamino)carbonylhydrazine (101M): a novel sulfonylhydrazine prodrug with broad-spectrum antineoplastic activity.
Cancer research 2001;61(7):3033-8.
2000: Philip G Penketh; Krishnamurthy Shyam; Alan C Sartorelli
Comparison of DNA lesions produced by tumor-inhibitory 1,2-bis(sulfonyl)hydrazines and chloroethylnitrosoureas.
Biochemical pharmacology 2000;59(3):283-91.
2000: Germana Rappa; Krishnamurthy Shyam; Aurelio Lorico; Oystein Fodstad; Alan C Sartorelli
Structure-activity studies of novobiocin analogs as modulators of the cytotoxicity of etoposide (VP-16).
Oncology research 2000;12(3):113-9.
1999: Krishnamurthy Shyam; Philip G Penketh; M Shapiro; Michael F Belcourt; Regina Loomis; S Rockwell; Alan C Sartorelli
Hypoxia-selective nitrobenzyloxycarbonyl derivatives of 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)hydrazines.
Journal of medicinal chemistry 1999;42(5):941-6.
1997: Philip G Penketh; Krishnamurthy Shyam; Alan C Sartorelli
Fluorometric assay for the determination of DNA-DNA cross-links utilizing Hoechst 33258 at neutral pH values.
Analytical biochemistry 1997;252(1):210-3.
1997: JA Sokoloski; Krishnamurthy Shyam; Alan C Sartorelli
Induction of the differentiation of HL-60 promyelocytic leukemia cells by curcumin in combination with low levels of vitamin D3.
Oncology research 1997;9(1):31-9.
1996: Philip G Penketh; Krishnamurthy Shyam; C L Patton; Alan C Sartorelli
Spectrophotometric assay for processes involving changes in hydrogen ion concentration in aqueous solution.
Analytical biochemistry 1996;238(1):46-9.
1996: Krishnamurthy Shyam; Philip G Penketh; R H Loomis; W C Rose; Alan C Sartorelli
Antitumor 2-(aminocarbonyl)-1,2-bis(methylsulfonyl)-1-(2-chloroethyl)- hydrazines.
Journal of medicinal chemistry 1996;39(3):796-801.
1996: Philip G Penketh; Krishnamurthy Shyam; Alan C Sartorelli
Mechanisms of resistance to alkylating agents.
Cancer treatment and research 1996;87():65-81.
1995: Philip G Penketh; Krishnamurthy Shyam; Alan C Sartorelli
Spectroscopic aqueous-phase assay for alkylating activity suitable for automation or multiwell plate application.
Analytical biochemistry 1995;231(2):452-5.
1994: Philip G Penketh; Krishnamurthy Shyam; Alan C Sartorelli
Studies on the mechanism of decomposition and structural factors affecting the aqueous stability of 1,2-bis(sulfonyl)-1-alkylhydrazines.
Journal of medicinal chemistry 1994;37(18):2912-7.
1993: Krishnamurthy Shyam; Philip G Penketh; A A Divo; R H Loomis; W C Rose; Alan C Sartorelli
Synthesis and evaluation of 1-acyl-1,2-bis(methylsulfonyl)-2-(2- chloroethyl)hydrazines as antineoplastic agents.
Journal of medicinal chemistry 1993;36(23):3496-502.
1992: Jonathan R Dimmock; S S Jonnalagadda; O A Phillips; E Erciyas; Krishnamurthy Shyam; Hugh A Semple
Anticonvulsant properties of some Mannich bases of conjugated arylidene ketones.
Journal of pharmaceutical sciences 1992;81(5):436-40.
1991: G Giordano; G Peterson; W J McMurray; Krishnamurthy Shyam; Alan C Sartorelli
The electron impact, chemical ionization and fast atom bombardment positive ion mass spectra of 1,2-bis(sulfonyl)methylhydrazines.
Biological mass spectrometry 1991;20(11):693-8.
1991: Jonathan R Dimmock; S A Patil; Krishnamurthy Shyam
Evaluation of some Mannich bases of 1-aryl-1-ethanones and related ketones for anticonvulsant activities.
Die Pharmazie 1991;46(7):538-9.
1991: Philip G Penketh; A A Divo; Krishnamurthy Shyam; C L Patton; Alan C Sartorelli
The effects of the methylating agent 1,2-bis(methylsulfonyl)-1-methylhydrazine on morphology, DNA content and mitochondrial function of Trypanosoma brucei subspecies.
The Journal of protozoology 1991;38(3):172-7.
1991: S Buddhu; Philip G Penketh; A A Divo; Krishnamurthy Shyam; C L Patton; Alan C Sartorelli
Enhancement of the trypanocidal activity of methyltriazenes in an animal model by the addition of an amidino group.
Acta tropica 1991;49(1):69-72.
1990: Krishnamurthy Shyam; Philip G Penketh; A A Divo; R H Loomis; C L Patton; Alan C Sartorelli
Synthesis and evaluation of 1,2,2-tris(sulfonyl)hydrazines as antineoplastic and trypanocidal agents.
Journal of medicinal chemistry 1990;33(8):2259-64.
1990: Philip G Penketh; Krishnamurthy Shyam; A A Divo; C L Patton; Alan C Sartorelli
Methylating agents as trypanocides.
Journal of medicinal chemistry 1990;33(2):730-2.
1989: G Pratviel; Krishnamurthy Shyam; Alan C Sartorelli
Cytotoxic and DNA-damaging effects of 1,2-bis(sulfonyl)hydrazines on human cells of the Mer+ and Mer- phenotype.
Cancer biochemistry biophysics 1989;10(4):365-75.
1988: D C Heimbrook; Krishnamurthy Shyam; Alan C Sartorelli
Novel 1-haloalkyl-2-nitroimidazole bioreductive alkylating agents.
Anti-cancer drug design 1988;2(4):339-50.
1987: Krishnamurthy Shyam; R T Hrubiec; R Furubayashi; L A Cosby; Alan C Sartorelli
1,2-Bis(sulfonyl)hydrazines. 3. Effects of structural modification on antineoplastic activity.
Journal of medicinal chemistry 1987;30(11):2157-61.
1986: R T Hrubiec; Krishnamurthy Shyam; L A Cosby; Alan C Sartorelli
Synthesis and evaluation of 1-(arylsulfonyl)-2-[(methoxycarbonyl)sulfenyl]-1-methylhydrazines++ + as antineoplastic agents.
Journal of medicinal chemistry 1986;29(9):1777-9.
1986: Krishnamurthy Shyam; R Furubayashi; R T Hrubiec; L A Cosby; Alan C Sartorelli
1,2-bis(arylsulfonyl)hydrazines. 2. The influence of arylsulfonyl and aralkylsulfonyl substituents on antitumor and alkylating activity.
Journal of medicinal chemistry 1986;29(7):1323-5.
1986: R T Hrubiec; Krishnamurthy Shyam; L A Cosby; R Furubayashi; Alan C Sartorelli
Synthesis and evaluation of 2-substituted 1-methyl-1-(4-tolylsulfonyl)hydrazines as antineoplastic agents.
Journal of medicinal chemistry 1986;29(7):1299-301.
1985: Krishnamurthy Shyam; L A Cosby; Alan C Sartorelli
Synthesis and evaluation of N,N'-bis(arylsulfonyl)hydrazines as antineoplastic agents.
Journal of medicinal chemistry 1985;28(4):525-7.
1985: Jonathan R Dimmock; Krishnamurthy Shyam; N W Hamon; S A Patil; P J Smith
bis-Mannich bases of styryl ketones as antileukemic agents.
Neoplasma 1985;32(1):85-91.
1985: Krishnamurthy Shyam; L A Cosby; Alan C Sartorelli
Relationship between structure and antineoplastic activity of (arylsulfonyl)hydrazones of 4-pyridinecarboxaldehyde.
Journal of medicinal chemistry 1985;28(1):149-52.
1984: Jonathan R Dimmock; Krishnamurthy Shyam; P J Smith
Decomposition of 1-aryl-3-dimethylamino-1-propanone methobromides under weakly acidic conditions.
Die Pharmazie 1984;39(7):467-70.
1984: Jonathan R Dimmock; Krishnamurthy Shyam; B M Logan; P J Smith; B M Cross
Syntheses and evaluation of some mannich bases derived from acetophenones against P388 lymphocytic leukemia and toxicological assessment of 3-dimethyl-amino-2-dimethylaminomethyl-1-(4-methoxyphenyl)-1-propanone dihydrochloride in rats.
Journal of pharmaceutical sciences 1984;73(4):471-7.
1983: Jonathan R Dimmock; Krishnamurthy Shyam; N W Hamon; B M Logan; S K Raghavan; D J Harwood; P J Smith
Evaluation of some Mannich bases derived from substituted acetophenones against P-388 lymphocytic leukemia and on respiration in isolated rat liver mitochondria.
Journal of pharmaceutical sciences 1983;72(8):887-94.