Synthesis of new photosensitizers with potential aplication in photodynamic therapy

• Grant number: 08/06619-4
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: June 01, 2009
• End date: May 31, 2013
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Kleber Thiago de Oliveira
• Grantee: Kleber Thiago de Oliveira
• Host Institution: Centro de Ciências Exatas e de Tecnologia (CCET). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Associated scholarship(s): 12/24092-9 - About the synthesis of Naphthalocyanine derivatives: Strategies Involving Organometallic Couplings and Methane[10]annulenes, BP.DR; 12/24096-4 - Tetrabromobacteriochlorins in Cross-Coupling Reactions: Approaches for the Synthesis of Highly Conjugated Systems, BP.DR; 12/14328-5 - 1,3-Dipolar Reactions on the Synthesis of Chlorins with low Aggregation, BP.IC; + associated scholarships 12/04964-1 - About the synthesis of benzophorphyrins derivatives with potential photosensitizing activities, BP.MS; 11/17177-5 - Total synthesis of new photosensitizers like benzopophyrins with potential activities in photodynamic therapy, BP.PD; 11/21102-0 - 1,3-Dipolar Reactions on the Synthesis of Chlorins with low Aggregation, BP.IC; 10/12545-3 - Total synthesis of hydrosoluble benzopophyrin derivatives with potential application in photodynamic therapy, BP.MS; 10/12549-9 - Synthetic Strategies to Prepare New Photosensitizers such as Phthalocyanines, BP.MS - associated scholarships

Abstract

In recent years, the photodynamic therapy (PDT) has occupied a place of prominence among the non-invasive therapies developed. Based on a combination of a photosensitizer and light with an appropriate wavelength, PDT has enabled the cure of several diseases, especially some types of cancer. Therefore, in this project is proposed the synthesis of new photosensitizers with the objective of contributing to the possible development of compounds for use in PDT. In part of this work is proposed the synthesis of new chlorins through the Diels-Alder reaction between protoporphyrin IX dimethyl ester and maleic anhydride. The adducts obtained should be converted into ethyleneglycol derivatives by the one-pot addition of ethyleneglycol and subsequently transformed in the esters of the 5-aminolevulinic acid (ALA), among other sulphonated compounds such as sultone and taurin. For this approach, some synthetic models were conveniently prepared. The total synthesis of new phthalocyanines linked to ALA among other hydrophilic groups (ascorbic acid and sugar) is also proposed in order to obtain compounds adequately functionalized to present a better solubility and reduced aggregation. In both synthesis (chlorins and phthalocyanines), it is expected an increase of the characteristics of the photosensitizers, highlighting the possibility to prepare the compound-type photosensitizer-ALA and also the occurrence of synergistic effect between the ALA and the photosensitizer when applied in PDT. By developing new macrocycles and new synthetic methodologies, this project would constitute a key effort for the consolidation of a group devoted to the synthesis of porphyrins and phthalocyanines. Besides, it would give support to several research groups and would establish important collaborations at the Chemistry Department of the FFCLRP-USP, together with other institutions where PDT-related researches are also being developed. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PETRILLI, RAQUEL; PRACA, FABIOLA S. G.; CAROLLO, ALINE REGINA H.; MEDINA, WANESSA S. G.; DE OLIVEIRA, KLEBER THIAGO; FANTINI, MARCIA C. A.; NEVES, MARIA DA GRACA P. M. S.; CAVALEIRO, JOSE A. S.; SERRA, OSVALDO A.; IAMAMOTO, YASSUKO; et al. Nanoparticles of Lyotropic Liquid Crystals: A Novel Strategy for the Topical Delivery of a Chlorin Derivative for Photodynamic Therapy of Skin Cancer. CURRENT NANOSCIENCE, v. 9, n. 4, p. 434-441, AUG 2013. (09/00009-2, 08/06619-4)

DOS SANTOS, G. A.; THOME, C. H.; FERREIRA, G. A.; YONEDA, J. S.; NOBRE, T. M.; DAGHASTANLI, K. R. P.; SCHEUCHER, P. S.; GIMENES-TEIXEIRA, H. L.; CONSTANTINO, M. G.; DE OLIVEIRA, K. T.; et al. Interaction of 10-(octyloxy) decyl-2-(trimethylammonium) ethyl phosphate with mimetic membranes and cytotoxic effect on leukemic cells. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, v. 1798, n. 9, p. 1714-1723, SEP 2010. (08/06619-4)

TORMENA, CLAUDIO F.; LACERDA, JR., VALDEMAR; DE OLIVEIRA, KLEBER T.. Revisiting the stability of endo/exo Diels-Alder adducts between cyclopentadiene and 1,4-benzoquinone. Journal of the Brazilian Chemical Society, v. 21, n. 1, p. 112-118, 2010. (05/59649-0, 08/06619-4)