Full text
| |
| Author(s): |
Marina Candido Primi
Total Authors: 1
|
| Document type: | Master's Dissertation |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) |
| Defense date: | 2013-08-26 |
| Examining board members: |
Elizabeth Igne Ferreira;
Chung Man Chin;
Claudete Justina Valduga
|
| Advisor: | Elizabeth Igne Ferreira |
| Abstract | |
Neglected diseases infect more than one billion people worldwide. However, a small fraction of the drugs registered in recent years is addressed to these pathologies. Leishmaniasis and Chagas\' disease are among the neglected diseases considered priority. Tuberculosis, which is no longer classified as a neglected disease by the World Health Organization, is also among the priorities of the Ministry of Health in Brazil. The therapeutic arsenal available for the treatment of those diseases comprehends drugs with high toxicity and increasing resistance, among other inconveniences. Thus, it is important the development of new drugs for those diseases. For this purpose, this study aimed at synthesizing hydroxymethylnitrofurazone (NFOH) drug targeted with mannan for the specific release in the macrophages. Prodrug design was used to achieve this goal by means of targeted drugs strategy towards increasing NFOH selectivity and potency. This lead compound has potential trypanocidal, leishmanicidal and tuberculostatic activity. The directing group used was a mannose polymer, mannan, which directs the release of the active compound to mannose receptors (MR) on macrophages surface. Due to the presence of Trypanosoma cruzi, Leishmania sp. and Mycobacterium tuberculosis inside macrophages during part of their life cycle, MR are considered a suitable target for specific release. In an attempt to obtain the proposed compound, several synthetic methods have been developed. Also, molecular modeling studies were carried out to obtain information about the targeted drug release. Due to the difficulty of obtaining NFOH derivative, the synthesis of metronidazole targeted drug was tried. Also molecular modeling studies to predict metronidazole release from mannan derivative were performed. (AU) | |
| FAPESP's process: | 11/03793-6 - Leishmanicidal, antichagasic and tuberculostatic candidates: synthesis of hydroxymethylnitrofurazone drug targeted with mannan for macrophages specific release |
| Grantee: | Marina Candido Primi |
| Support Opportunities: | Scholarships in Brazil - Master |