| Grant number: | 13/18160-4 |
| Support Opportunities: | Regular Research Grants |
| Start date: | January 01, 2014 |
| End date: | December 31, 2015 |
| Field of knowledge: | Health Sciences - Pharmacy |
| Principal Investigator: | Roberto Parise Filho |
| Grantee: | Roberto Parise Filho |
| Host Institution: | Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil |
| City of the host institution: | São Paulo |
Abstract
Currently, cancer is a leading cause of death worldwide. Although there are many drugs for cancer control, problems such as low selectivity and high toxicity stimulate the search for new antitumor molecules. Natural products have played an important role in the introduction of new drugs or even as molecular patterns in order to obtain new bioactive substances. Recent studies reported that capsaicinoids and capsinoids, substances found in several species of peppers, have presented considerable antiproliferative effect by inducing selective apoptosis in tumors. Thus, the use of these compounds as structural models for the synthesis of analogues with potentially higher activity is a subject of great interest. Thus, this project aims to synthesize capsaicinoids and capsinoids analogues, using molecular modification strategy (hybridization, bioisosterism and homology), evaluate their antiproliferative activity, and propose new analogues from theoretical models obtained by quantitative structure-activity relationship (QSAR). The analogues will be synthesized using classical methodologies such as acylation, sulfonylation and thioacylating and subsequently they will be evaluated for their cytotoxic capacity in normal and tumor cells. Regarding the most promising analogues, pro-apoptotic properties and activity on the cell cycle will be explored in order to elucidate the mode of action of those compounds. In order to identify similarities between the compounds molecular properties, chemometric approaches will be applied to classify all synthesized compounds. Moreover, with the determination of experimental data (IC50), mathematical models (multivariate QSAR) will be constructed and validated for the prediction of new chemical entities with potential antitumor activity. It is hoped that new anticancer agents could be obtained, which may benefit public health in control of the disease. (AU)
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