Edmond J. LaVoie

Professor of Medicinal Chemistry

Chair, Department of Pharmaceutical Chemistry

Ph.D. 1975, State University of New York-Buffalo

Phone (732) 445-2674;

fax (732) 445-6312

e-mail: elavoie@rci.rutgers.edu

Current Interests:

Our primary research interests are in the discovery and the development of novel pharmaceuticals. For several years our research group has focused on the design and synthesis of novel non-camptothecin topoisomerase I-targeting antitumor agents. Several potent topoisomerase I-targeting agents have been identified. Studies are in progress to identify among these compounds the more promising candidates for development into the clinic. Recently, studies in our laboratory have been undertaken to develop agents that will selectively bind and stabilize G-quadruplex DNA. We are presently exploring the promise and full potential of these G-quadruplex stabilizers in cancer chemotherapy. In addition, our research group has initiated research into the discovery of new lead compounds for the development of isozyme specific topoisomerase II-targeting agents for the future development of an improved clinical agent within this class of cancer chemotherapeutic agents.

Recent publications (representative):

Barbieri, C.M., Srinivasan, A.R., Rzuczek, S.G., Rice, J.E., LaVoie, E.J., and Pilch, D.S. (2007) Defining the mode, energetics and specificity with which a macrocyclic hexaoxazole binds to human telomeric G-quadruplex DNA. Nucleic Acids Res., 35(10): 3272-3286.

Minhas, G.S., Pilch, D.S., Kerrigan, J.E., LaVoie, E.J., and Rice, J.E. (2006) Synthesis and G-quadruplex stabilizing properties of a series of oxazole-containing macrocycles. Biorg. Med. Chem. Lett., 16: 3891-3895.

S. Zhu, A. L. Ruchelman, N. Zhou, A. Liu, L. F. Liu, and E. J. LaVoie (2006) 6-Susbstituted 6H-Dibenzo[c,h]naphthyridine-5-ones: Reversed Lactam Analogues of ARC-111 with Potent Topoisomerase I-targeting Activity and Cytotoxicity, Bioorg. Med. Chem., 14: 3131-3143.

S. Zhu, A. L. Ruchelman, N. Zhou, A. Liu, L. F. Liu, and E. J. LaVoie, (2005), Derivatives of 2,3-Dimethoxy-8,9-methylenedioxybenzo[i]phenathridiene-12-carboxylic acid with Potent Topoisomerase I-targeting Activity and Cytotoxicity. Bioorg. Med. Chem., 13: 6782-6794.

A. L. Ruchelman, N. Zhou, A. Liu, L. F. Liu, and E. J. LaVoie, (2005), 5-(2-Aminoethyl)dibenzo[c,h][1,6]naphthyridin-6-ones: Variation of N-Alkyl Substituents Modulates Sensitivity to Efflux Transport Associated with Multidrug Resistance, J. Med. Chem., 48: 792-804.

A. L. Ruchelman, S. Zhu, N. Zhou, A. Liu, L. F. Liu, and E. J. LaVoie, (2004), Dimethoxybenzo[i]phenanthridine-12-carboxylic acid Derivatives and 5H-dibenzo[c,h]naphthyridin-5-ones with Potent Topoisomerase I-Targeting Activity and Cytotoxicity, Bioorg. Med. Chem. Lett., 14: 5585-5589.

Ruchelman, A.R., Singh, S.K., Liu, A., Zhou, N., Liu, L.F., LaVoie E.J., (2004), Cytotoxicity of 5H-dibenzo[c,h][1,6]-naphthyridin-6-ones and 6H-indeno[1,2-c]isoquinolin-5,11-diones in tumor cells sensitive and resistant to camptothecin analogues, Letters in Drug Design and Discovery, 1: 198-202.

Ruchelman, A.R., Li, T-K., Angela Liu, A., Liu, L.F, LaVoie, E.J. (2004) Nitro and Amino Substitution within the A-ring of 5H-8,9-dimethoxy-5-(2-N,N-dimethylaminoethyl)dibenzo[c,h][1,6]naphthyridin-6-ones: Influence on Topoisomerase I-Targeting Activity and Cytotoxicity, Bioorg. Med. Chem., 14: 3731-3742.

Ruchelman, A.L., Singh, S.K. Ray, A., Wu, X., Yang, J-M., Nai Zhou, N., Liu, A., Liu, L.F., LaVoie, E.J. (2004), 11H-Isoquino[4,3-c]cinnolin-12-ones: novel anticancer agents with potent topoisomerase I-targeting activity and cytotoxicity, Bioorg. Med. Chem., 12: 795-806.

Kwon, M-J., LaVoie, E. J., Kim, J. S. (2003), Topoisomerase I inhibition by 2-substituted 5-nitrobenzimidazoles. Yakhak Hoechi , 47: 125-129.

Li, T-K., Houghton, P.J., Desai, S.D., Daroui, P., Liu, A.A., Hars, .S., Alexander L. Ruchelman, A.L., LaVoie, E.J., Liu, L.F., (2003), Characterization of ARC-111 as a novel topoisomerase I-targeting anticancer agent, Cancer Res., 63: 8400-8407.

Li, D., Zhao, B., Sim, S-P., Li,Ti-K., Liu, L. F., and LaVoie, E J. (2003), 8,9-Methylenedioxybenzo[i]phenanthridines as Topoisomerase I-Targeting Anticancer Agents, Bioorg. Med. Chem., 11: 3795-3805.

Singh, S. K., Ruchelman, A. L., Zhou, N., Liu, A., Liu, L. F., and LaVoie, E. J. (2003), Aza-Analogs of Dibenzo[c,h]Cinnoline: Triazachrysenes as Potent Topoisomerase I-Targeting Anticancer Agents, Med. Chem. Res., 12: 1-12.

Kerrigan, J. E., Pilch, D. S., Ruchelman, A. L., Li, T-K., Liu, A., Liu, L. F., and LaVoie, E. J. (2003), 5H-8,9-Dimethoxy-5-(2-N,N-dimethylaminoethyl)dibenzo[c,h][1,6]naphthyridin-6-ones and Related Compounds as TOP1-Targeting Agents: Influence of Structure on the Ternary Cleavable Complex Formation, Bioorg. Med. Chem. Lett., 13: 3395-3399.

Singh, S.K., Ruchelman, A.L., Li, T-K, Liu, A., Liu, L.F. and LaVoie, E.J. (2003), Nitro and amino substitution in the D-ring of 5-(2-dimethylaminoethyl)-2,3-methylenedioxy-5H-dibenzo[c,h][1,6]naphthyridin-6-ones: Effect on topoisomerase-I targeting activity and cytotoxicity, J. Med. Chem., 46: 2254-2257.

Ruchelman, A.L., Singh, S.K., Wu X.H., Yang, J-M., Li, T-K., Liu, A., Liu, L.F. and LaVoie, E.J., (2003), 5H-Dibenzo[c,h]1,6-naphthyridin-6-ones: Novel topoisomerase I-targeting anticancer agents with potent cytotoxic activity, Bioorganic Med. Chem., 11: 2061-2073.

Yu, Y., Singh, S. K., Liu, A., Li, T-K., Liu, L.F. and LaVoie E.J., (2003), Substituted dibenzo[c,h]cinnolines: Topoisomerase I-targeting anticancer agents, Bioorganic Med. Chem., 11: 1474-1491.

Li, D., Zhao ,B., Sim ,S-P., Li, T-K., Liu, A., Liu, L.F., and LaVoie, E.J. (2003), 2,3-Dimethoxybenzo[i]phenanthridines: Topoisomerase I-targeting anticancer agents, Bioorganic Med. Chem., 11: 521-528.

Makhey, D., Li, D., Zhao, B., Sim, S-P., Li, T-K., Liu, A., Liu, L.F., LaVoie, E.J., (2003), Substituted benzo[i]phenanthridines as mammalian topoisomerase-targeting agents, Bioorganic Med. Chem., 11: 1809-1820.

Pilch, D.S., Liu, H-Y., Li, T-K., LaVoie, E.J. and Barbieri, C.M. (2002), Defining the molecular interactions that are important for the poisoning of human topoisomerase I by benzimidazoles and terbenzimidazoles, In Small Molecule DNA and RNA Binders: From Synthesis to Nucleic Acid Complexes, Martine Demeununck, Christian Bailly, and David Wilson, eds., Wiley-VCH, Weinheim, Germany, pp 576-608.

Ruchelman, A.L., Singh, S.K., Wu, X.H., Ray, A., Yang, J-M., Li, T-K., Liu, A., Liu, L.F. and LaVoie, E.J., (2002), Diaza- and triazachrysenes: Potent topoisomerase-targeting agents with exceptional antitumor activity against the human tumor xenograft, MDA-MB-435, Bioorg. Med. Chem. Lett., 12: 333-3336.

Zhu, N., Sheng, S., Li, D., LaVoie, E.J., Karwe, M.V., Rosen, R.T., and Ho, C.-T., (2001), Antioxidative flavonoid glycosides from Quinoa seeds (Chenopodium quinoa Willd), J. Food Lipids, 8: 37-44, 2001

Wang, H-m., Mao, Y., Chen, A., Zhou, N., LaVoie, E.J., and Liu, L.F., (2001), Stimulation of topoisomerase II-mediated DNA damage by a mechanism involving protein thiolation, Biochemistry, 40: 3316-3323.

Jin, S., Kim, J.S., Sim, J.S., Sim, S-P., Liu, A., Pilch, D.S., Liu, L.F., and LaVoie, E.J., (2000) Heterocyclic bibenzimidazole derivatives as topoisomerase I inhibitors, Bioorg. & Med. Chem. Lett., 10: 719-723.

Xu, Z., Li, T-K., Bathory, E., LaVoie, E.J., Srinivasan, A.R, Olson, W.K., Sauers. R.R., Liu, L.F., and Pilch, D.S., (2000) Human topoisomerase I poisoning by protoberberines: Potential roles for both drug-DNA and drug-enzymes interactions.  Biochemistry, 39: 7107-7116.

Ranagarajan, M., Kim, J.S., Sim, S-P., Liu, A., Liu, L,F., and LaVoie, E.J., (2000) Topoisomerase I inibition and cytotoxicity of 5-bromo and 5-phenylterbenzimidazoles, Bioorganic & Med. Chem., 8: 2591-2600. 

Zhu, N.Q., Huang, T.C., Yu, Y.N., LaVoie, E.J., Yang, C.S., Ho, C.T. (2000) Identification of oxidation products of (-)-epigallocatechin gallate and (-)-epigallocatechin with H202. J. Agric. Food Chem., 48: 979-981.

Li, D., Zhao, B., and LaVoie, E.J., (2000) Nitroarylstannes as synthons for the preparation of benzo[i]phenanthridines and phenanthridine derivatives, J. Org. Chem., 65: 2802-2805.

Ranagarajan, M., Kim, J.S., Song, J., Sim, S-P., Liu, A., Pilch, D.S., Liu, L,F., and LaVoie, E.J., (2000) 2”-Substituted 5-phenylterbenzimidazoles as topoisomerase I poisons, Biooganic & Med. Chem., 8: 1371-1382. 

Wang, M., Shao, Y., Li, J., Zhu, N., Rangarajan, M., LaVoie, E.J., and Ho, C-T. (1999), Antioxidative phenolic glycosides from sage (Salvia officinalis), J. Nat. Prod., 62454-6,

Makhey, D., Yu, C., Liu, A., and Liu, L.F. Liu, and LaVoie, E.J., (2000) Substituted benz[a]acridines as antineoplastic aegnts:  A novel class of topoisomerase I poisons, Biooganic & Med. Chem., 8: 1171-1182.

Sanders, M.M., Liu, A., Li, T-K., S. Desai, LaVoie, E.J., Makhey, D., and Liu, L.F., (1998)  Selective cytotoxicity of topoisomerase-directed protoberberines against glioblastoma cells, Biochem. Pharmacol., 56: 1157-1166.

Xu, Z., Li, T-K., Kim, J.S., LaVoie, E.J., Breslauer, K.J., Liu, L.F. and Pilch, D.S. (1998) DNA minor groove binding-directed poisoning of human DNA topoisomerase I by terbenzimidazoles, Biochemistry, 37: 3558-3566.

Wang, M., Shao, Y., Li, J., Zhu, N., Rangarajan, M., LaVoie, E.J., and Ho, C-T., (1998) Antioxidative phenolic compounds from sage (Salvia officinalis), J. Agric. Food Chem., 46: 4869-4873.

Kim, J. S., Gatto B., Yu, C., Liu, A., Liu, L.F. and LaVoie, E.J. (1998) Quantitative structure activity of substituted terbenzimidazoles as topoisomerase I poisons, Bio-organic Medicinal Chemistry, 6: 163-172.

Pilch, D.S., Xu, Z., Sun. Q., LaVoie, E.J., Liu, L.F., and Breslauer, K.J., (1997) A terbenzimidazole that preferential binds and conformationally alters sructurally distinct DNA duplex domains:  A potential mechanism for topoisomerase I poisoning, Proc. Natl. Acad. Sci. USA, 94: 13565-13570.

Sim, S.P., Gatto, B. , Yu, C. Liu, A.A., Li, T.K., Pilch, D.S., LaVoie, E.J. and Liu, L.F., (1997) Differential poisoning of topoisomerases by menogaril and nagalamycin dictated by the minor groove-binding nogalose sugar, Biochemistry, 36: 13285-13291.

Pilch, D.S., Yu, C., Makhey, D., LaVoie, E.J., Breslauer, K.J., Geacintov, N.E., and Liu, L.F., (1997)  DNA minor groove-directed and intercalative ligand-DNA interactions in the poisoning of human DNA topoisomerase I by protoberberine analogs, Biochemistry, 36: 12542-12553.

Yang, J-M., Sullivan, G. F., Makhey, D. B., LaVoie, E. J., and Hait, W. N., (1997) Inhibitory effect of alkylating modulators on the function of P-glycoprotein, Oncology Research, 9: 477-484.

Kim, J. S., Gatto B., Yu, C., Liu, A., Liu, L.F. and LaVoie, E.J. (1997) Terbenzimidazoles: Influence of 2"-,4- and 5-substituents on cytotoxicity and relative potency of topoisomerase I poisons, Journal of Medicinal Chemistry, 40: 2818-2824.

Goldman, G.H., Yu, C., Sanders, M.M., LaVoie, E.J., and Liu, L.F. (1997) Differential poisoning of human and Aspergillus nidulans DNA topoisomerase I by Bi- and Terbenzimidazoles, Biochemistry, 36: 6488-6494.

Kim, J. S., Gatto B., Yu, C., Liu, A., Liu, L.F. and LaVoie, E.J. (1996) Substituted 2,5’-Bi-1H-benzimidazoles: Topoisomerase I inhibition and cytotoxicity, Journal of Medicinal Chemistry, 39: 992-998.

Kim, J.S., Sun, Q., Gatto, B., Yu, C., Liu, A., Liu, L.F., and LaVoie, E.J. (1996) Structure-activity relationships of benzimidazoles and related heterocycles as topoisomerase I poisons, Bioorganic & Medicinal Chemistry, 4: 621-630.

Makhey, D., Gatto, B., Yu, C., Liu, A., and Liu, L.F, and LaVoie, E.J. (1996) Coralyne and related compounds as inhibitors of mammalian topoisomerase I and II, Bioorganic & Medicinal Chemistry, 4: 781-791.

Pilch, D.S., Xu, Z., Sun, Q., LaVoie, E.J., Liu, L.F., Geacintov, N.E., and Breslauer, K.J. (1996) Characterizing the DNA Binding Modes of a Topoisomerase I-Poisoning Terbenzimidazole: Evidence for both Intercalative and Minor Groove Binding Properties, Drug Design and Discovery, 13: 115-133.

Sun, Q. and LaVoie, E.J. (1996) Synthesis of benzimidazo[2,1-a]isoquinoline and their 5,6-dihydrobenzimidazo[2,1-a]isoquinolines, Heterocycles, 43: 737-743.

Stevens, G.J., LaVoie, E.J., and McQueen, C.A. (1996) The role of N-acetylation in the mutagenicity of the antitumor agent, batracylin, Carcinogenesis, 17: 115-119.

Hecht, S.S., Rivenson, A., Amin, S., El-Bayoumy, K., Reddy, B.S., Kurtzke, C., and LaVoie, E.J. (1996) Mammary carcinogenicity in female CD rats of diol epoxide metabolites of benzo[j]fluoranthene, Cancer Letters, 251-255.

Patani, G. and LaVoie, E.J. (1996) "Bioisosterism: A Rationale Approach in Drug Design", Chemical Reviews. 96: 3147-3176.

Gatto, B., Sanders, M.M., Yu, C., Wu, H-Y., Makhey, D., LaVoie, E.J., and Liu, L.F. (1996) Identification of topoisomerase I as the cytotoxic target of the protoberberine alkaloid coralyne, Cancer Research., 56: 2795-2800.

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