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| Author(s): |
Soraya da Silva Santos
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) |
| Defense date: | 2012-09-12 |
| Examining board members: |
Elizabeth Igne Ferreira;
Claudete Justina Valduga;
Carlota de Oliveira Rangel Yagui
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| Advisor: | Elizabeth Igne Ferreira |
| Abstract | |
Leishmaniasis is considered a superneglected tropical disease and affects primarily areas of extreme poverty. It represents an emergent illness with high morbidity and mortality. About 20 different species of intracellular parasites of Leishmania spp. have been identified as pathogenic. Those protozoans are transmitted to human hosts by means of the female phlebotomine sandflies bite. The chemotherapy is scarce, limited, and expensive. The drugs available can cause undesirable side effects and there are already reports of the increased number of drug resistance. Considering that, the discovery and the development of new leishmanicide agents are urgently needed, the objective of this work as to contribute to this search using the method of molecular modification, prodrug design. Taken into account that dendrimers can be used as drug carriers, the purpose of this work was the synthesis of first generation dendrimer targeted drugs of hydroxymethylnitrofurazone (NFOH), that shows potential leishmanicide activity. Thus, we designed NFOH targeted drugs with selective action in macrophages, due to the presence of mannose in the structure, and also NFOH targeted drugs that present selectivity for the parasite, due to the presence of inositol in the structure. Several synthetic methods have been used with the aim of synthesizing the targeted dendrimers with NFOH. Synthetic studies suggested the targeted dendrimers of D-mannose and of myo-inositol have been obtained, although impure and without the bioactive agent. The major difficulty was the purification of the compounds. In addition, molecular modeling methods were applied to understand the bioactive compound releasing from the first generation leishmanicide targeted dendrimers. Molecular features as spatial hindrance and electrostatic potential were evaluated to predict which region would be the most available to an enzymatic action regarding the bioactive compound release. (AU) | |
| FAPESP's process: | 10/03651-4 - Potential leishmanicides: synthesis of first generation hydroxymethylnitrofural drug targeted dendrimers |
| Grantee: | Soraya da Silva Santos |
| Support Opportunities: | Scholarships in Brazil - Master |