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| Author(s): |
Tiago Zaminelli
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas |
| Defense date: | 2018-03-09 |
| Examining board members: |
Gilberto De Nucci;
Edson Antunes;
Sisi Marcondes;
Marcelo Nicolas Muscara;
Soraia Katia Pereira Costa
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| Advisor: | Gilberto De Nucci |
| Abstract | |
The increased levels of cyclic nucleotides (cGMP and cAMP) in enterocytes trigger intracellular mechanisms of ion and fluid secretion into the lumen causing secretory diarrhea. Twelve novel pyridopyrimidines derived from 5-(3,5-bistrifluoromethylphenyl)-1,3-dimethyl-5,11-dihydro-1H-indeno[2,1:5,6]pyrido[2,3-d]pyrimidine-2,4,6-trione (FPIPP) were synthesized and evaluated on intracellular cyclic nucleotide accumulation. All compounds had no effect on either cyclic nucleotide basal levels or on pre-contracted aortic rings. The metabolic activity and viability in T84 cells, assessed by MTT and LDH assays respectively were not affected by incubation with the compounds (50 µM). Compound VI almost abolished cGMP accumulation (94% inhibition) induced by STa toxin in T84 cells and significantly decreased (69%) forskolin-induced cAMP accumulation in Jurkat cells. Compound VI was found to be active in an in vivo model for diarrhea in rabbits. In vitro stability test revealed that compound VI is resistant to oxidation promoted by atmospheric oxygen (AU) | |
| FAPESP's process: | 13/15525-1 - Synthesis and evaluation of antidiarrheal activity and bioavailability of new pyridopyrimidines analogs |
| Grantee: | Tiago Zaminelli |
| Support Opportunities: | Scholarships in Brazil - Doctorate |