Project 2. Combination of synthesis, imaging and genetic model in vivo: innovative approach from Brazil and Australia for the pre-clinical and clinical development of anticancer drugs
This project aims to combine Brazilian and Australian efforts in the pre-clinical studies of two compounds of Brazilian biodiversity, pisosterol and 2,3,9-trimethoxypy- terocarp, which had their cytotoxic potentials previously proven by our research group through cellular and molecular studies. Pisoterol is a cytotoxic blocker of the amplification of the MYC oncogene in leukemia and glioblastoma cell lines. The amplification of MYC is a mechanism associated with the invasion and aggressiveness of many tumors, and its inhibition is of great value in anticancer therapy. 2,3,9-trimethoxypyrotecarpane is a non-tubulinic, selectively cytotoxic agent for tumor cells, therefore with fewer side effects on non-proliferative cells when compared to tubulin antimitotics. These results strongly suggest that both natural products are promising antitumor compounds and justify further studies, combining synthesis of derivatives, imaging tests, and essays with genetic models of cancer to validate them as new antitumor drugs. The development of the project will require innovative techniques in organic synthesis and pre-clinical drug development, based on “omic” techniques, “high-content” analyzes and in vivo trials with more reliable genetic models of cancer. The validation of two natural products as new leading antitumor compounds may be of great interest to the pharmaceutical industry, especially the Brazilian industry, which imports 90% of the drugs in clinical use. In addition, the identification of new antitumor drugs originating from Brazilian biodiversity will project Brazil into the scenario of drug development. The project will involve a multidisciplinary research team, UFC, and the Australian National University (ANU, Australia), which has already established an official cooperation agreement. The Brazilian team will be composed of researchers from graduate programs as Pharmacology (CAPES 6), Chemistry (CAPES 6) and Medical Sciences (CAPES 6), while the Australian team will be composed of researchers from the Cancer Therapy Group (College of Medicine, Biology and Environment) and the School of Research in Chemistry. It is noteworthy that the Australian group has strong collaboration with international pharmaceutical industries and that the Australian university (ANU) is ranked as the 20th best university in the world.
