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Synthesis, characterization, and solubility study of new crystalline forms of antineoplastic agents

Abstract

Neoplasms have been the leading cause of most deaths recorded annually worldwide. Scientists are engaged in research to continuously improve the treatment of the most diverse types of cancer. Therefore, the main objective of this project is to optimize the performance of the drug candidate LASSBio-1735, both through the development of new crystalline forms and through its controlled release. The crystal structure of LASSBio-1735 - an N-acylhydrazone derivative that exhibited in vitro antiproliferative activity against HL-60 (human leukemia), SF-295 (human glioblastoma), MDA-MB435 tumor cells (melanoma) and HCT-8 (ileocecal adenocarcinoma) - which was determined by our research group, will be the basis for the synthesis and investigation of the physical-chemical properties of the new crystalline forms (salts, hydrates, solvates and/or co-crystals). It is extremely important to study the interaction of the new crystalline forms obtained with the biological system; therefore, cell viability will be evaluated by MTT in neoplastic cell lines compared to healthy cell lines, as well as the evaluation of hemolytic activity. The antineoplastic action will be evaluated based on the relationship between the gene expression of inflammatory markers and oxidative stress, tumor growth, and toxicity assessment. Balb/c mice will be used and inoculated with Ehrlich tumor cells for this. These animals will be treated in different periods and groups. (AU)

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