Synthesis and pre-clinical evaluation of the (-)-o-methylcubebin, drug candidate to treat shistosomiasis, and (-)-hinokinin, drug candidate to treat Chagas' Disease, both obtained from (-)-cubebin isolated from dry seeds of Piper cubeba

• Grant number: 07/05322-5
• Support Opportunities: Research Grants - Research Partnership for Technological Innovation - PITE
• Start date: May 01, 2010
• End date: April 30, 2014
• Field of knowledge: Physical Sciences and Mathematics - Chemistry
• Principal Investigator: Márcio Luís Andrade e Silva
• Grantee: Márcio Luís Andrade e Silva
• Host Institution: Pró-Reitoria Adjunta de Pesquisa e Pós-Graduação. Universidade de Franca (UNIFRAN). Franca , SP, Brazil
• Company: JP Indústria Farmacêutica S/A
• City: Franca
• Associated researchers: Ademar Alves da Silva Filho ; Jairo Kenupp Bastos ; Rosangela da Silva de Laurentiz ; Sérgio de Albuquerque ; Wilson Roberto Cunha

Abstract

The goal of this proposal is the development of two new potential drugs for the treatment of shistosomiasis and Chagas' disease, and both drug candidates were protected by two patents that have been deposited at INPI (Brazilian National Institute for Industrial Protection). These drugs will be developed in collaboration with the pharmaceutical company: JP Indústria Farmacêutica LTDA. Shistosomiasis affects more than 220 million people annually world wide, from which 10 million are in Brazilian territory. About 30 % of the infected individuals are resistant to the available treatments, using the commercial medicines. With regard to Chagas disease, there is no treatment available, since previous used drugs, nifurtimox and benzonidazol are no longer commercialized. The two new dybenzylbutyrolactone compounds, (-)-O-methylcubebin and (-)-hinokinin will be obtained, by partial synthesis, from (-)-cubebin, which will be isolated from the seeds of Piper cubeba. Both drugs will be used, respectively, for the treatment of schistosomiasis and Chagas' diseases. It should be pointed out that both compounds were active in both in vitro and in vivo assays and that they are also found in plants. To undertake the pre-clinical evaluation in animals, it will be produced 1.5 kg of each compound. The pre-clinical studies in animals will be undertaken by using two rodent animal models, mice and rats, and one non-rodent animal model, rabbits. The studies will be undertaken for 24 weeks at the CPQBA-UNICAMP, following official protocols (ANVISA "OECD 407/95”, and Resolution CNS 251/97). The drugs will be administered by intramuscular route using an adequate pharmaceutical formulation. (AU)