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Synthesis and investigation of new crystalline forms of antineoplastic agents


This project's primary goal is to optimize the antineoplastic drug melphalan's performance and the lead compound LASSBio-1735 by developing new crystalline forms and drug release methods. Since melphalan - an antineoplastic drug used to treat breast and ovarian cancer and multiple myeloma - has no known crystal structure, the first stage of this project and, consequently, the first result to be obtained will be the determination of its crystal structure. The analysis of the crystal structure and the packing of melphalan as well as LASSBio-1735 - an N-acylhydrazone derivative that has displayed in vitro antiproliferative activity against HL-60 (human leukemia), SF-295 (human glioblastoma), MDA-MB435 (melanoma), and HCT-8 (ileocecal adenocarcinoma) tumor cells - will be the basis for the synthesis and investigation of the physicochemical properties of the new crystalline forms (salts, hydrates, solvates, and/or co-crystals). This project also aims to synthesize and functionalize magnetite nanoparticles for the controlled release of antineoplastic compounds. The evaluation of antineoplastic action will be carried out based on the relationship between the gene expression of inflammatory markers and oxidative stress, tumor growth, and toxicity assessment. For this, Balb/c mice will be used, inoculated with Ehrlich tumor cells. These animals will be treated in different periods and groups. (AU)

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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)
PINHEIRO, LUCAS BARBOZA MOREIRA; TAO, SONGSHENG; CULBERTSON, ELIZABETH; DE ARAUJO, GABRIEL LIMA BARROS; BILLINGE, SIMON J. L.; FERREIRA, FABIO FURLAN. Evaluation of the polymorphic forms of ritonavir and lopinavir in raw materials and co-milled systems. International Journal of Pharmaceutics, v. 628, p. 9-pg., . (17/16499-5, 21/03640-7)
FERREIRA, FABIO F.; PEREIRA, ALINE P. C.; REIS, IANNY B.; SASAKI, BIANCA R. S.; FAVARO, WAGNER J.; DURAN, NELSON. Quantitative phase analysis of commercial ammonium phosphates by PXRD for application in biological systems. Powder Diffraction, v. N/A, p. 12-pg., . (18/10052-1, 20/03419-6, 21/03640-7)

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