Full text
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| Author(s): |
João Paulo Menezes Spadeto
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Instituto de Química |
| Defense date: | 2022-03-03 |
| Examining board members: |
Rodrigo Antonio Cormanich;
Nelson Henrique Morgon;
Osmair Vital de Oliveira
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| Advisor: | Rodrigo Antonio Cormanich |
| Abstract | |
This dissertation was divided into 2 chapters corresponding to the studies developed along with the Master’s degree program: 1) Fluorinated dihydropyridines as candidates to block L-type voltage-dependent Calcium Channels – it was studied the L-type Calcium Channel Protein, responsible for causing diseases such as Alzheimer, cardiovascular disorders, hypertension, arrhythmia, among other. Among the most prescribed drugs in the United States, one may highlight amlodipine and nifedipine. The human L-type Calcium Channel protein was constructed using the software Prime by Schrodinger, presenting 69% sequence identity with a rabbit’s L-type Calcium Channel protein, code 5GJV on Protein Data Bank. Modified dihydropyridines were proposed, all containing trifluoromethyl functional groups in common, in which the ligand 14 showed lower XP Glidescore than nifedipine, yet amlodipine remained with the lowest score. From the Molecular Dynamics and MM/PBSA results, ligands 8, 15 and 16 showed higher stability than nifedipine and amlodipine, making them possible candidates for drugs. 2) Modified chondroitin sulfates capable of interacting with DBL3x: Revisiting the work Docking and molecular Dynamics of potential drugs to DBL3: a proposal for the treatment of malaria - This research project comes from my work of completing a course done in 2019, which was necessary to redo all the results to be published in the Journal of Biomolecular Structure and Dynamics. In Sub- Saharan Africa, Malaria cases affect, on average, 24 million pregnant women annually. The infection by P. falciparum during pregnancy is asymptomatic and can cause fetal death or of the disease host. The protein associated with Plasmodium falciparum infection in human erythrocyte (DBL3x) was studied, which is responsible for causing vascular clogging. Analogs of Chondroitin Sulfate A, B and C were proposed. DBL3x was prepared using the Protein Preparation Tool by Schrodinger. Docking results show that all proposals presented a more intense interaction with the protein than CSA. However, Molecular Dynamics simulations showed that only CPB and CPC ligands tend to stabilize the system in a time interval of 100 ns (AU) | |
| FAPESP's process: | 20/06536-3 - Fluorinase reactive substrate analysis |
| Grantee: | João Paulo Menezes Spadeto |
| Support Opportunities: | Scholarships in Brazil - Master |