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Associate Professor
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B.Sc., (Universidad Autónoma de Guadalajara, Mexico)
M.Sc. (UAG-Ehime University, Japan)
Ph.D. (University of Alberta, Canada)
Office: S-410
Lab: S-411
Mailing Address:
Dr. G. Ulibarri
Department of Chemistry & Biochemistry
Laurentian University
Sudbury, ON
P3E 2C6
Telephone:(705) 675-1151, ext 2107, 2125
FAX: (705) 675-4844
Internet:
gulibarri@laurentian.ca
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New approaches to medicinal chemistry: anticancer
Our group is interested in selectively treating cancer through; increasing the bioavailability of antineoplastic drugs, developing new approaches to exploit the differences between normal and malignant cells, and developing new drugs based on rational design with their proper SAR studies.
Drug Delivery mediation via Nanoparticles: Pharmaceutical companies have had great difficulties developing an efficient system that delivers a drug candidate only to the desired target, especially for the treatment of cancer. The main problems reside within the solubility profile of the molecule or its metabolic degradation, the later leading either to a fast clearance of the organic material or to toxicity. Lack of hydrophilicity and aggregation may be the most serious problems confronting the distribution of a medical agent throughout the body. These factors obviously affect the final concentration of the active principle at the required site. Thus, means to protect and safely deliver the active ingredient are of great interest.
When the active site is within the nuclear envelope, as is the case for all DNA intercalating/alkylating agents, intact drug delivery is a great challenge. New methods targeting the nucleus using the cellular active transport to deliver chemicals will increase the possibility of adequate administration of the drug. However, in order to benefit from this type of transport, the size of the particles is of primordial importance due to the limited pore sizes at the nuclear membrane (<9 nm).
Circular Telomerase Inhibitors: Our knowledge of the cell machinery is increasing continuously and new targets have started to appear as potential ways to expand our anticancer arsenal. Recent research has shown that the telomerase enzyme plays a prominent role in the control of ‘immortality’ of a cell. Further research has shown that inhibiting this enzyme diminishes the rate of tumor growth. Thus, the search of novel telomerase inhibitors is an emerging research topic within the scientific community. Telomestatin is a novel natural product with high telomerase affinity. Its circular structural motif presents research opportunities other than enzyme inhibition, such as nanotube formation, and thus possibilities of drug delivery mechanisms.
Closing the tap on Tumor Blood Supply-Angiolytic Approach: The regulation of nutrient supply to a tumor is a promising approach for their destruction or size reduction. Tumors can obtain nutrients through two mechanisms: dispersion from the surrounding environment or through blood vessels. Dispersion is adequate for small tumors, but as it grows, angiogenic factors are released in order to create new blood vessels that will eventually supply the tumor of the needed nutrients. Once the tumor is comfortable with the amount of nutrients it has obtained, it begins to release anti-angiogenic factors (e.g. angiostatin/endostatin) to limit further blood vessel development. These factors control the formation of new blood vessels, not only for itself, but also from neighboring tumors. Large amounts of anti-angiogenic drugs are in clinical development stages.
One strategy is to limit tumor growth by destroying the existing blood vessels (angiolysis), thus limiting the nutrient intake of the already large tumor, which forces it to shrink in size. This strategy can lead to better control of the tumor size and progression of the existing cancer, thereby improving the possibilities of finding an alternative/complementary tumor treatment. In essence, we wish to develop a method to reduce cerebral tumor size, which if left untreated, can lead to ominous consequences.
Selected Publications:
Synthesis and in vitro cytotoxicity evaluation of 4-aminoquinoline derivatives.
Zhang H, Solomon VR, Hu C, Ulibarri G, Lee H.
Biomed Pharmacother. 2008 Feb;62(2):65-9. Epub 2007 May 24.
The efficacy and selectivity of tumor cell killing by Akt inhibitors are substantially increased by chloroquine.
Hu C, Solomon VR, Ulibarri G, Lee H.
Bioorg Med Chem. 2008 Sep 1;16(17):7888-93. Epub 2008 Jul 29.
A. Kassam, G. Bremmer, B. Clark, G. Ulibarri and R. B. Lennox. Place Exchange Reactions of Alkyl Thiols on Gold Nanoparticles. J. Am. Chem. Soc., 128 (11): 3476-3477 (2006)
Studies Toward the Construction of the Allyltrisulfide Component in Esperamicin-A1 From 5-Ketoshikimic Acid Derivatives: Part 2, Piguel, S.; Ulibarri, G.; Grierson, D. Tetrahedron Letters, 1999, 40, 295.
Studies Toward the Construction of the Allyltrisulfide Component in Esperamicin-A1 From 5-Ketoshikimic Acid Derivatives: Part 1, Piguel, S.; Ulibarri, G.; Grierson, D. S. . Tetrahedron Letters, 1999, 40, 291.
Homocamptothecins (hCPTs): Synthesis and Antitumor Activity of Novel E-Ring Modified Camptothecin Analogues. Lavergne, O.; Lesueur-Guinot, L.; Pla Rodas, F.; Kasprzyk, P. G.; Pommier, J.; Demarquay, D.; Prevost, G.; Ulibarri, G.; Rolland, A.; Schiano-Liberatore, A-M.; Harnett, J.; Pons, D.; Chabrier de Lassaunière, P-E.; Bigg, D. C. H. The Journal of Medicinal Chemistry, 1998, 41 (27), 5410.
Strategies for the Synthesis of the « Enediyne » Antitumor Antibiotics Calicheamicin ?1I / Esperamicin A1 and Mechanism Based Analogues. Ulibarri, G.; Audrain, H.; Lhermitte, H.; and Grierson, D. S. In « New Horizons in Organic Synthesis (IUPAC) », Pages 46-60, Ed. V. Nair and S. Kumar, New Age International, Wiley Eastern (1997).
Activation of Imidazolides Using Methyl Trifluoromethanesulfonate: A Convenient Method for the Preparation of Hindered Esters and Amides. Ulibarri, G.; Choret, N. and Bigg, D. C. H. Synthesis, 1996, 1286.
Synthesis of the 'Enediyne' Antibiotic Esperamicin-A1, and Novel Analogues for Tumor Targeting. Ulibarri, G.; Audrain, H.; Nadler, W.; Lhermitte, H. and Grierson, D. S. Pure and Applied Chemistry, 1996, 68, 601.
Construction of the Bicyclic Core Structure of the Enediyne Antibiotic Esperamicin-A1 in either Enantiomeric Form from (-)-Quinic Acid. Ulibarri, G.; Nadler, W.; Skrydstrup, T; Audrain, H.; Chiaroni, A.; Riche, C. and Grierson, D. S. J. Org. Chem., 1995, 60, 2753.
Patents:
Analogues of camptothecin, their use as medicaments and the pharmaceutical compositions containing them. Bigg; D; Lavergne; O; Pla Rodas; F; Pommier; J; Ulibarri; G; Harnett; J; Rolland; A; Liberatore; A-M; Lanco; C; Cazaux; J-B; Le Breton; C; Manginot; E, US6,815,546, November 9, 2004.
Derivatives of N-(iminomethy)amines, their preparation, their use as medicaments and the pharmaceutical compositions containing them. Bigg; D; Chabrier de Lassauniere; P-E; Auvin; S; Harnett; J; Ulibarri; G, US6,809,090,. October 26, 2004
Analogues of camptothecin, their use as medicaments and the pharmaceutical compositions containing them, Pla Rodas, F; Cazaux, J-B; Le Breton, C; Liberatore, A-M; Bigg, D; Harnett, J; Manginot, E; Rolland, A; Pommier, J; Uibarri, G; Lanco, C; Lavergne, O, US 6,797,715, Sept. 28, 2004.
Analogues of camptothecin, their use as medicaments and the pharmaceutical compositions containing them, Bigg; D; Lavergne; O; Pla Rodas; F; Pommier; J; Ulibarri; G; Harnett; J; Rolland; A; Liberatore; A-M; Lanco; C; Cazaux; J-B; Le Breton; C; Manginot; E, US 6,762,301, July 13, 2004.
2-aminopyridine derivatives, their use as medicines and pharmaceutical compositions containing them, Chabrier de Lassauniere; P-E; Auvin; S; Harnett; J; Pons; D; Ulibarri; G; Bigg; D, US 6,762,176, July 13, 2004.
New derivatives of N-(iminomethy)amines, their preparation, their use as medicaments and the pharmaceutical compositions containing them, Auvin; S; Bigg; D; Ulibarri; G; Chabrier de Lassauniere; P-E; Harnett; J; US2004097494, May 20, 2004.