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Application of biophotonics in the study of the interactions of alkaloids isomoschatoline and palmatine with targeted vectors and correlation with their biological effects

Grant number: 14/09980-0
Support type:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): August 18, 2014
Effective date (End): August 17, 2015
Field of knowledge:Health Sciences - Pharmacy
Principal Investigator:Marcos José Salvador
Grantee:Caroline Caramano de Lourenço
Supervisor abroad: Stéphanie Bonneau
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Local de pesquisa : Université Pierre et Marie Curie (Paris 6), France  
Associated to the scholarship:11/18315-2 - CHEMICHAL, biological and biotechnological studies by Annonaceae species (Annona cacans, Annona squamosa, Annona mucosa or Guatteria hispida), BP.DR

Abstract

Research of natural products has been a simple and successful strategy that has contributed to new drug discovery with technological application (Harvey, 2000). In industrialized countries, 25% of prescribed drugs contain at least one active constituent derived from the plant kingdom. However, in the therapeutics, the number of available drugs for the treatment of infectious diseases and neoplastic tumors is highly restricted due to low-efficiency and non-specific targeting. These limitations can be related to low solubility, toxicity, cellular resistance and long-term treatment (Soares & Cury, 2001). Drug delivery systems can be used in order to improve the effectiveness and bioactive molecules therapeutic index. Among them we may cite Cyclodextrins (CDs), Amphiphilic block copolymer micelles (abpM) and Low-density-lipoproteins (LDL) or LDL-like particles. Drug delivery by nanovectors involves complexes processes, all of them aiming to result in a selective drug releasing system. Thus, we aim to generate and implement knowledge for improving bioactive alkaloids hydro-solubility and chemical stability. We will focus our research on spectroscopic characterization of alkaloids-carrier complexes. We also intend to evaluate the effect of these interactions in biological models such as model membranes, microorganism (bacteria and yeast) and cell cultures (tumor lines). Finally we aim to investigate the impact on intracellular localization of these alkaloids due to carrier's complexation and the consequences on biological effect. The France and Brazilian groups are going to combine their complementary expertises and join forces to elucidate the role of natural products bioactivity and to study the interaction of the alkaloids present in native plant species with nanovectors and correlation with biological effects. Moreover, one important limitation of their use is related to their hydrophobic character with this research we intend to solve this problem. We then want to evaluate various strategies of vectorization to improve their biological activities. Accordingly, the general focus of our project is to study the dynamics of natural products interactions (isoquinoline alkaloids, such as, isomoschatoline and palmatine with nanocarriers (lipoproteins, cyclodextrins or nanoparticles). We will explore chemical and biological properties of the products, primarilly aiming for possible applications in microobiology and infectology. In this context, a particular attention will be paied on the potential photo-activities of the mentionned natural products. The Palmatine (PA) (purity > 99%) is obtained from Sigma Aldrich. The isomoschatoline (ISO) was obtained by isolation from the crude methanol extract of the bark of the native Brazilian species Guatteria hispida. The alkaloid isolation and characterization was conducted at the Laboratory of Pharmacognosy, Bioscience and Technology of Bioactive Products, Institute of Biology, College of Pharmacy, UNICAMP, Campinas, Brazil under the guidance of Prof. Dr. Marcos Jose Salvador. With this material the tests relevant will be held to cover the proposed objectives of this project will be held under the guidance of Professor. Dr. Stephanie Bonneau. through an internship with the laboratory "Jean Perrin, CNRS UMR 8237, Université Pierre et Marie Curie, Paris, France. The solid complexes are obtained and absorption measurements are made in a UV-VIS spectrophotometer. Will evaluate the toxic effects of alkaloids on human fibroblast culture (strain HS68) by measuring the cytocidal effect after treatment with alkaloids in the dark and without exposure to light irradiation. Be carried out flow cytometric assays and cellular uptake of photosensitizing complexed with LDL plus co-location trials and tests involving antimicrobial PDT. (AU)