Department of Chemistry Biochemistry

ROBERT PETTIT

Regents' Professor
Ph.D., Wayne State University, 1956

  Office: PSD-301  Lab: PS C-334/D-307
  Phone: (480)965-3351  Lab Phone: (480)727-2009
  Fax: (480) 965-2747
  Email: bpettit@asu.edu

Research and Teaching Interests

Significant advances in the treatment of human cancer and other serious medical problems are becoming increasingly more dependent upon scientists well trained in organic chemistry, biochemistry and biology. Our group is organized to provide the specialized training necessary to undertake problems concerned with the discovery of anticancer substances for the treatment of cancer. Among various activities, we are pursuing a unique program concerned with isolation, structural identification and synthesis of naturally occurring anticancer agents from marine animals, plants, and arthropods. Studies concerned with synthetic methods, and routes to certain important biosynthetic products comprise related areas of interest.

Specific Research Interests: Chemistry of natural products (peptides, nucleotides, and steroids), cancer chemotherapy (anticancer agents from arthropods, marine animals and plants), and total synthesis of natural products.

Selected Publications

"Antineoplastic Agents 595. Structural Modifications of Betulin and the X-ray Crystal Structure of an Unusual Betulin Amine Dimer.1a ," G. Pettit, N. Melody, F. Hempenstall, J-C. Chapuis, T. Groy, L. Williams, Journal of Natural Products 77(4) 863-872 (2014)

"Isolation and Structure of Axistatins 1-3 from the Republic of Palau Marine Sponge Agelas axifera," G.R. Pettit, Y. Tang, Q. Zhang, G.T. Bourne, F. Hogan, C. Arm, J.C. Knight, R.K. Pettit, J-C. Chapuis, D. Doubek, F. Ward, and J.N.A. Hooper, Journal of Natural Products 76(3) 420-424 (2013)

"Synthesis of a 2-Aryl-3-Aroyl-Indole Salt (OXi8007) Resembling Combretastatin A-4 with Application as a Vascular Disrupting Agent ," M. Hadimani, M. MacDonough, T. Strecker, R. Lopez, M. Sriram, B. Nguyen, R. Kessler, A. Ghatak, A. Shirali, L. Liu, C. Garner, G. Pettit, E. Hamel, D. Chaplin, R. Mason, M.L. Trawick, K. Pinney, Journal of Natural Products 76(9) 1668-1678 (2013)

"Preclinical Efficacy of Sodium Narcistatin to Reduce Inflammation and Joint Destruction in Rats with Adjuvant-Induced Arthritis," Cheri Lubahn, Jill A. Schaller, Eric Shewmacker, Carlo Wood, Denise L. Bellinger, Donna Byron, Noeleen Melody, George R. Pettit, and Dianne Lorton, Rheumataology International 32(12) 3751-3760 (2012)

"Auristatin Drugs Decrease Long-Term Suvivin Levels and Induce Apoptosis in Human Pancreatic Cancer (Panc-1) Cells," J.S. Park, M.M. Asuncion, J.R. Aspe, G.R. Pettit and N.R. Wall, Journal of Investigative Med. 60 148-149 (2012)

"Antineoplastic Agents 587. Isolation and Structure of 3-Epipancratistatin from Narcissus v. Ice Follies," G.R. Pettit, G.H. Bao, N. Melody, R. Tan, D.L. Doubek, S. Gao, and L. Williams, Journal of Natural Products 75 771-773 (2012)

"Antineoplastic Agents 548. Synthesis of Iodo- and Di-iodocomstatin Phosphate Prodrugs," G.R. Pettit, H.J. Rosenberg, R. Dixon, J.C. Knight, E. Hamel, J-C. Chapuis, R.K. Pettit, F. Hogan, B. Sumner, K.B. Ain, and B.B. Trickey-Platt, Journal of Natural Products 75 385-393 (2012)

"The Cephalostatins 22. Synthesis of a Bis-steroidal Pyrazine Pyrones.," G.R. Pettit, B.R. Moser, R.F. Mendonca, Journal of Natural Products 75(6) 1063-1069 (2012)

"Antineoplastic Agents 592. Highly Effective Cancer Cell Growth Inhibitory Structural Modifications of Dolastatin 10," G.R. Pettit, F. Hogan, S. Toms, J. Nat. Prod. 74 962-968 (2011)

"A chemifluoriscent immunoassay for the determination of marinobufagenin in body fluids.," D. Abi-Ghanem, X. Lai, L.R. Bergman, D. Horvat, J. Li,, D. Romo, M.N. Uddin, Y. Kamano, T. Nogawa, J-P. Xu, G.R. Pettit, and J.B. Puschett, J. Immunoassay & Immunochemistry 32 31-46 (2011)

"Interactions of Halichondrin B and Eribulin with Tubulin," R. Bai, T.L. Nguyen, J.C. Buurnett, O. Atasoylu, M.H.G. Munro, G.R. Pettit, A.B. Smith, R. Gussio, and E. Hamel, J. Chem. Information and Modeling 51 1393-1404 (2011)

"Antineoplastic Agents 590. X-Ray Crystal structure of Dolastatin 16 and Syntheses of the Dolamethylleuine and Dolaphenvaline Units," G.R. Pettit, T.H. smith, J.-P. Xu, D.L. Herald, E.J. Flahive, C.R. anderson, P.E. Belcher, and J.C. Knight, Journal of Natural Products 74 1003-1008 (2011)

"The Cephalostatins 21. Synthesis of Bis-steriodal Pyrazine Rhamnorides," G.R. Pettit, R.F. Mendonca, J.C. Knight, and R.K. Pettit, Journal of Natural Products 74 1922-1930 (2011)

"Regioselective Synthesis of a Water Soluble Monophosphate Derivatives of Combretastatin A-1," R. Tanpure, N. Rajendra, B. Nguyen, T. Trecker, S. Aquirre, S. Sharma, D.J. Chaplin, B. Siim, E. Hamel, J. Lippert G.R. Pettit, M.L. Trawick, and K.G. Pinney, Journal of Natural Products 74 1568-1574 (2011)

"Isolation of Human Cancer Cell Growth Inhibitory, Antimicrobial Lateritin from a Mixed Fungal Culture," R.K. Pettit, G.R. Pettit, J.-P. Xu,C. A. Weber, and L. Richert, Planta Medica 76 500-501 (2010)

"Antineoplastic Agents 582. Isolation and Structure of a Cyclobutane-type Sesquiterpene Cancer Cell Growth Inhibitor from Coprinus cinereus.," G.R. Pettit, Y. Meng, R.K. Pettit, D.L. Herald, and Z.A. Cichacz, Bioorg. Med. Chem. 18 4879-4883 (2010)

"Potentiation of the activity of cisplatin in a human colon tumour xenograft model by auristatin PYE, a structural modification of dolastatin 10.," E. M. Prokopiou, P. A. Cooper, G. R. Pettit, M. C. Bibby, and S. D. Shnyder, Molecular Medicine Reports 3 309-313 (2010)

"Antineoplastic Agents. 573. Isolation and structure of papilistatin from the papilionid butterfly Byasa polyeuctes termessa," G. R. Pettit, Q.-H. Ye, D. L. Herald, F. Hogan, and R. K. Pettit, Journal of Natural Products 73 164-166 (2010)

"An efficient synthetic strategy for obtaining 4-methoxy carbon isotope labeled combretastatin A-4 phosphate and other Z-combretastatins," G. R. Pettit, M. D. Minardi, F. Hogan, and P. M. Price, Journal of Natural Products 73 399-403 (2010)

"Antineoplastic Agents. 556. Isolation and Structure of Coprinastatin 1 from Coprinus cinereus," G. R. Pettit, Y. Meng, R. K. Pettit, D. L. Herald, Z. A. Cichacz, D. L. Doubek, and L. Richert, Journal of Natural Products 73 388-392 (2010)

"Isolation of Human Cancer Cell Growth Inhibitory, Antimicrobial Lateritin from a Mixed Fungal Culture," R. K. Pettit, G. R. Pettit, J.-P. Xu, C. A. Weber, and L. Richert, Planta Medica 76 500-501 (2010)

"Antineoplastic Agents 582. Isolation and Structure of a Cyclobutane-type sesquiterpene Cancer Cell Growth Inhibitor from Coprinus cinereus," G. R. Pettit, Y. Meng, R. K. Pettit, D. L. Herald, and Z. A. Cichacz, Bioorg. Med. Chem. 18 4879-4883 (2010)

"E-Combretastatin and E-Resveratrol Structural Modifications: Antimicrobial and Cancer Cell Growth Inhibitory â-E-Nitrostyrenes," R. K. Pettit, G. R. Pettit, E. Hamel, F. Hogan, B. R. Moser, S. Wolf, S. Pon, J.-C. Chapuis, J. M. Schmidt, Bioorganic and Medicinal Chemistry 17 6606-6612 (2009)

"Antineoplastic Agents 579. Synthesis and Cancer cell Growth Evaluation of E-Stilstatin 3, a Resveratrol Structural Modification. ," G. R. Pettit, N. Melody, A. Thornhill, J. C. Knight, T. L. Groy, and C. L. Herald, Journal of Natural Products 72 1637-1642 (2009)

"Antineoplastic Agents. 578. Synthesis of Stilstatins 1 and 2 and Their Water-Soluble Prodrugs," G. R. Pettit, A. Thornhill, N. Melody, and J. C. Knight, Journal of Natural Products 72 380-388 (2009)

"Antineoplastic Agents. 570. Isolation and Structure Elucidation of Bacillistatins 1 and 2 from a Marine Bacillus Silvestris," G. R. Petti, J. C. Knight, D. L. Herald, R. K. Pettit, F. Hogan, V. J. R. V. Mukku, J. S. Hamblin, M. J. Dodson II, and J.-C. Chapuis, Journal of Natural Products 72 366-371 (2009)

"Density functional study on the structural conformations and intramolecular charge transfer from the vibrational spectra of the anticancer drug combretastatin-A2," L. Padmaja, C. Ravikumar, D. Sajan, I. Hubert Joe, V. S. Jayakumar, G. R. Pettit, and O. Faurskov Nielsen, Journal of Raman Spectroscopy 40 419-428 (2009)

"Antineoplastic Agents. 565. Synthesis of Combretastatin D-2 Phosphate and Dihydro-combretastatin D-2.," G. R. Pettit, P. D. Quistorf, J. A. Fry, D. L. Herald, E. Hamel, and J.-C. Chapuis , Journal of Natural Products 72 876-883 (2009)

"Cytotoxic Lipid Esters from Peucedanum ledebourielloides," X. Zheng, J. Du, Y. Xu, D. Liao, and G. R. Pettit, Medicinal Chemistry Research in press (2009)

"Antineoplastic Agents. 454. Synthesis of the Strong Cancer Cell Growth Inhibitors trans-Dihydronarciclasine and 7-Deoxy-trans-dihydronarciclasine.," G. R. Pettit, S. Ducki, S. A. Eastham, and N. Melody, Journal of Natural Products 72 1279-1282 (2009)

"Antineoplastic agents. 575. The fungus Aspergillus phoenicis.," G. R. Pettit, J. Du, R. K. Pettit, J. C. Knight, D. L. Doubek, Heterocycles 79 909-916 (2009)

"Intracellular Activation and Deactivation of Tasidotin, an Analog of Dolastatin 15: Correlation with Cytotoxicity," R. Bai, M. C. Edler, P. L. Bonate, T. D. Copeland, G. R. Pettit, R. F. Ludueña, and E. Hamel, Molecular Pharmacology 75 218-226 (2009)

"Antineoplastic Agents. 571. Total Synthesis of Bacillistatin 2.," G. R. Pettit, S. Hu, J. C. Knight, and J. C. Chapuis, Journal of Natural Products 72 372-379 (2009)

""In Vivo Activity of Anprocide Alone, and In Vitro Activity in Combination With Conventional antibiotics Against Staphylococcus aureus and S. epidermidis Biofilms," ," R. K. Pettit, C. A. Weber, S. B. Lawrence, G. R. Pettit, M. J. Kean, G. D. Cage, Journal of Medical Microbiology 58 1203-1206 (2009)

"Application of a High Throughput Alamar Blue Biofilm Susceptibility Assay to Staphylococcus aureus Biofilms," R. K. Pettit, C. A. Weber, and G. R. Pettit, Ann. Clin. Microbiol. Antimicrob. 8 no pps. (2009)

"Spongistatin 1: A New Chemosensitizing Marine Compound that Degrades XIAP," L. Schyschka, A. Rudy, I. Jeremias, N. Barth, G. R. Pettit, A. M. Volmar, Leukemia 22 1737-1745 (2008)

"Antineoplastic Agents. 558. Ampelocissus sp. Cancer Cell Growth Inhibitory Constituents," G. R. Pettit, V. J. Mukku, G. Cragg, D. L. Herald, J. C. Knight, C. L. Herald, J-C. Chapuis, Journal of Natural Products 71 130-133 (2008)

"Stylopeptide 2, a Proline-Rich Cyclodecapeptide from the Sponge Stylotella sp.," M. R. Brennan, C. E. Costello, S. D. Maleknia, G. R. Pettit, K. L. Erickson, Journal of Natural Products 71 453-456 (2008)

"Synthesis and Biological Evaluation of Phorboxazole Congeners Leading to the Discovery and Preparative-Scale Synthesis of (+)-Chlorophorboxazole A Possessing Picomolar Human Solid Tumor Cell Growth Inhibitory Activity," A. B. Smith III, T. M. Razler, R. M. Meis, G. R. Pettit, Journal of Organic Chemistry 73 1201-1208 (2008)

"Combretastatin Dinitrogen-Substituted Stilbene Analogues as Tubulin-Binding and Vascular-Disrupting Agents," R. Siles, J. Freeland Ackley, M. B. Hadimani, J. J. Hall, B. E. Mugabe, R. Guddneppanavar, K. A. Monk, J-C. Chapuis, G. R. Pettit, D. J. Chaplin, K. Edvardsen, M. L. Trawick, C. M. Garner, K. G. Pinney, Journal of Natural Products 71 313-320 (2008)

"Antineoplastic Agents. 536. New Sources of Naturally Occurring Cancer Cell Growth Inhibitors from Marine Organisms, Terrestrial Plants, and Microorganisms," G. R. Pettit, F. Hogan, J-P. Xu, R. Tan, T. Nogawa, Z. A. Cichacz, R. K. Pettit, J. Du, Q-H. Ye, G. M. Cragg, C. L. Herald, M. S. Hoard, A. Goswami, J. Searcy, L. Tackett, et al., Journal of Natural Products 71 438-444 (2008)

"In vitro Interactions of Approved and Experimental Drugs against Candida albicans and Aspergillus spp.," K. K. Repp, F. Hogan, G. R. Pettit, and R. K. Pettit, Journal of Chemotherapy 20 137-139 (2008)

"Vibrational Spectra and ab initio Molecular Orbital Calculations of the Novel Anticancer Drug Combretastatin A-4 Prodrug," C. James, G. R. Pettit, O. F. Nielsen, V. S. Jayakumar, I. Hubert Joe, Spectrochimica Acta, Part A: Molecular and Biomolecular Spectroscopy 70 1208-1216 (2008)

"Design, Synthesis, Biochemical, and Biological Evaluation of Nitrogen-Containing Trifluoro Structural Modifications of Combretastatin A-4," J. J. Hall, M. Sriram, T. E. Strecker, J. K. Tidmore, C. J. Jelinek, G. D. Kishore Kumar, M. B. Hadimani, G. R. Pettit, D. J. Chaplin, M. L. Trawick, and K. G. Pinney, Bioorg. Med. Chem. Lett. 18 5146-5149 (2008)

"Antineoplastic Agents 552. Oxidation of Combretastatin A-1 and Trapping the Ortho-Quinone Intermediate Considered A Key Metabolic Product of the Corresponding Phosphate Prodrug," G. R. Pettit, A. J. Thornhill, B. R. Moser, and F. Hogan, Journal of Natural Products 71 1561-1563 (2008)

"Role of Smac in Cephalostatin-Induced Cell Death," A. Rudy, N. Lopez-Anton, N. Barth, G. R. Pettit, V. M. Dirsch, K. Schulze-Osthoff, M. Rehm, J. H. Prehn, M. Vogler, S. Fulda, A. M. Vollmar, Cell Death and Differentiation 15 1930-1940 (2008)

"Auristatin PYE, a novel synthetic derivative of dolastatin 10, is highly effective in human colon tumor models.," S. D. Shnyder, P. A. Cooper, N. J. Millington, G. R. Pettit, M. C. Bibby, International Journal of Oncology 31 353-360 (2007)

"Antineoplastic Agents 560. Isolation and Structure of Kitastatin 1 from an Alaskan Kitasatospora sp.," G.R. Pettit, R. Tan, R.K.Pettit, T.H. Smith, S. Feng, D.L. Doubek, L. Richert, J. Hamblin, C. Weber and J-C. Chapuis, J. Nat. Prod. 70 1069-1072 (2007)

"Antineoplastic Agents 561. Total Synthesis of Respirantin ," G.R. Pettit, T.H. Smith, S. Feng, J.C. Knight, R. Tan, R.K. Pettit and P.A. Hinrichs, J. Nat. Prod. 70 1073-1083 (2007)

"Antineoplastic Agents 550. Synthesis of 10b (S) - epipancratistatin from (+) - Narciclasine," G.R. Pettit, N. Melody, D.L. Herald, J.C. Knight and J-C. Chapuis, J. Nat. Prod. 70 417 (2007)

"Comparison of the Activities of the Truncated Halichondrin B Analog NSC 707389 (E7389) with those of the Parent Compound and a Proposed Binding Site on Tubulin," D.A. Dabydeen, J.C. Burnett, R.B. Bai, P. Verdier-Pinard, M.J. Yu, B.A.Littlefield, S.J.H. Hickford, G.R. Pettit, J.W. Blunt, M.H.G. Munro, R. Gussio and E.' Hamel, Molecular Pharmacology 70 1866 (2006)

"Antineoplastic Agents 554. The Manitoba Bacterium Streptomyces sp.," G.R. Pettit, J.Du, R.K. Pettit, L.A. Richert, V. Mukku and M.S. Hoard, J. Nat. Prod 69 804-806 (2006)

"Isolation and Structural Modification of 7-Deoxynarciclasine and 7-deoxy-trans-dihydronarciclasine," G.R. Pettit, S.A. Eastham, N. Melody, B. Orr, D.L. Herald, J. McGregor, J.C. Knight, D.L. Doubek, G.R. Pettit III, L.C. Garner and J.A. Bell, J. Nat. Prod. 69 7-13 (2006)

"Design and Synthesis of a Potent Phorboxazole C (11-15) Acetal Analogue," A.B. Smith, T.M. Razler, R.M. Meis and G.R. Pettit, Organic Letters 8 797-799 (2006)

"Design, Synthesis, and Biological Evaluation of Combretastatin Nitrogen-Containing Derivatives as Inhibitors of Tubulin Assembly and Vascular Targeting Agents," K.A. Monk, R. Siles, M. Hadimani, B.E. Mugabe, F. Ackley, K. Edvardsen, M.L. Trawick, C.M. Garner, M.R. Rhodes, G.R. Pettit and K.G. Pinney, BioOrg. Med. Chem. 14 3231-3234 (2006)

"Antineoplastic Agents. 551. Isolation and Structures of Bauhiniastatins 1-4 from Baihinia purpurea," G.R. Pettit, A. Numata, C. Iwamoto, Y. Usami, T. Yamada, H. Ohishi and G.M. Cragg, J. Nat. Prod. 69 323-327 (2006)

"Marinobufagenin Impairs First Trimester Cytotrophoblast Differentiation ," H. L. LaMarca, C. A. Morris, G. R. Pettit, T. Nogawa, J. B. Puschett , Placenta 27 984-988 (2006)

"The Marine Invertebrate Constituent Cephalostatin 1 Activates an ER Stress- Specific and Apoptosome-Independent Apoptotic Signal Pathway ," N. Lopez-Anton, A. Rudy, N. Barth, I. M. Mueller, L. Schmitz, G.R. Pettit, V. M. Dirsch and A. M. Vollmar, J. Biol. Chem. 281 33078-33086 (2006)

"Cyclotrimerization approach to unnatural structural modifications of pancratistatin and other amaryllidaceae constituents – Synthesis and biological evaluation," T. Hudlicky, M. Moser, S. C. Banfield, U. Rinner, J-C. Chapuis, and G. R. Pettit, Canadian Journal of Chemistry 84 1313-1337 (2006)

"Antineoplastic Agents 509. Synthesis of Sodium Fluorcombstatin Phosphate and Related 3-Halo-Stilbenes," G.R. Pettit, M.D. Minardi, H.J. Rosenberg, E. Hamel, M.C. Bibby, S.W. Martin, M.K. Jung, R.K. Pettit, T.J. Cuthbertson and J-C. Chapuis, J. Nat. Prod. 68 1450-1458 (2005)

"In vitro and In vivo Antifungal Activities of the Marine Sponge Constituent Spongistatin 1," R.K. Pettit, S. Pon, Z.A. Cichacz, C.L. Herald, G.R. Pettit and T. Woyke, Medical Mycology 43 453-463 (2005)

"Antitumor Studies of Auristatin PYE, a NovelSynthetic Derivative of Dolastatin 10," M.C. Bibby, P.A. Cooper, N.J. Millington, G.R. Pettit, and S.D. Shnyder, Clin. Cancer Res. 11 9089S-9089S (2005)

"Investigation of the Efficacy and Mechanism of Action of Pancratistatin 3, 4-cyclic Phosphate," S.D. Shnyder, P.A. Cooper, J.J. Millington, J.H. Gill, G.R. Pettit and M.C. Bibby, Clin. Cancer Res. 11 8971S-8971S (2005)