Post-doctorate fellow in search of new drugs against Hypercholesterolemia, based on specific genetic and epigenetic markers of the Brazilian population

• Grant number: 19/06172-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: May 01, 2019
• End date: November 30, 2021
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Fausto Feres
• Grantee: Glaucio Monteiro Ferreira
• Host Institution: Instituto Dante Pazzanese de Cardiologia (IDPC). Fundação Adib Jatene (FAJ). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 17/50342-6 - Institutional development plan in research (PDIp), AP.PDIP
• Associated scholarship(s): 19/24112-9 - Novel HMG-CoA reductase inhibitors development by integrating dyslipidemic patients' genetic studies and molecular modelling, BE.EP.PD

Abstract

Statins are the most commonly prescribed medications in the world. However, although considered safe, they are associated with several adverse effects, mainly those related to Myalgia and Rhabdomyolysis and other muscular symptoms related to the use of statins (SMRE), about 65% of cases of low adherence. These characteristics of statins can impair primary and secondary prevention, which consequently leads to increased morbidity, hospitalizations and mortality due to cardiovascular diseases, burdening the Unified Health System (SUS). Pharmacogenetic studies associate the risk of SMRE with profile of DNA variants. Therewith, used genetic informations for development of new drugs using strategies in silico and in vitro. The purpose of this study is using genetic information from hyperlipidemic and SMRE patients to understand molecular interactions associated with the adverse effect and to develop new structures of HMG-CoA reductase inhibitors (HMGCR) with improved efficacy and safety. For this, the variants identified by high-throughput sequencing, in a study in progress at the Dante Pazzanese Institute, with potential alteration of functional effect, support the studies of molecular interaction by Computer-Aided Drug Design (CADD), for the construction of three-dimensional models between protein structures (with and without mutations). In silico studies performed to search for new potential ligands against HMGCR based on the constructed models. Thus, new drug planning studies follow two strategies to search for these possible new bioactive compounds: Ligand Based Drug Design (LBDD) and Structure Based Drug Design (SBDD). Such as, molecular docking, molecular force fields (MIF's), virtual screening, enzymatic kinetic tests of HMGCR inhibition and structural optimization. This studies, search to link Molecular Biology and Medicinal Chemistry in the constructed for new drugs with against Hypercholesterolemia, contributing to the increase of therapeutic adherence, with consequent reduction of the risks of cardiovascular events and direct costs to the public health. (AU)

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SOUZA, CAMILA O.; TEIXEIRA, ALEXANDRE A. S.; BIONDO, LUANA AMORIM; SILVEIRA, LOREANA SANCHES; DE SOUZA BREDA, CRISTIANE N.; BRAGA, TARCIO T.; CAMARA, NIELS O. S.; BELCHIOR, THIAGO; FESTUCCIA, WILLIAM T.; DINIZ, TIEGO A.; et al. Palmitoleic acid reduces high fat diet-induced liver inflammation by promoting PPAR-gamma-independent M2a polarization of myeloid cells. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, v. 1865, n. 10, OCT 2020. (13/04765-1, 19/06172-4, 19/24112-9, 15/19530-5, 16/01409-8)

SILVA, JOAO VITOR; SAVINO, DEBORA; HIRATA, MARIO HIROYUKI; FERREIRA, GLAUCIO MONTEIRO; GIAROLLA, JEANINE. Zika Virus NS2B-NS3 Protease: Quantum Chemical Properties Insights into Designing Inhibitory Peptides. PROTEIN AND PEPTIDE LETTERS, v. 29, n. 11, p. 10-pg., 2022-01-01. (19/06172-4)

DOS SANTOS, BENEDITO MATHEUS; FERREIRA, GLAUCIO MONTEIRO; TAVARES, MAURICIO TEMOTHEO; DE BONA, JULIO CESAR; HIRATA, MARIO HIROYUKI; DE PAULA, VANDERLUCIA FONSECA; SATURNINO, KLAUS CASARO; SOARES, ANDREIMAR MARTINS; MENDES, MIRIAN MACHADO. Antiophidic activity of the secondary metabolite lupeol isolated from Zanthoxylum monogynum. Toxicon, v. 193, p. 38-47, APR 15 2021. (19/06172-4, 16/12899-6, 19/24112-9)

FERREIRA, GLAUCIO MONTEIRO; KRONENBERGER, THALES; MALTAROLLO, VINICIUS GONCALVES; POSO, ANTTI; GATTI, FERNANDO DE MOURA; ALMEIDA, VITOR MEDEIROS; MARANA, SANDRO ROBERTO; LOPES, CARLA DUQUE; TEZUKA, DAIANE YUKIE; DE ALBUQUERQUE, SERGIO; et al. Trypanosoma cruzi Sirtuin 2 as a Relevant Druggable Target: New Inhibitors Developed by Computer-Aided Drug Design. PHARMACEUTICALS, v. 16, n. 3, p. 14-pg., 2023-03-01. (16/22365-9, 19/06172-4, 17/25543-8)

GUTIERREZ, ALVARO; FERREIRA, GLAUCIO MONTEIRO; MACHUCA, JUAN; VENTHUR, HERBERT; FERES, FAUSTO; HIRATA, MARIO HIROUYKI; HIRATA, ROSARIO DOMINGUEZ CRESPO; CERDA, ALVARO. Characterization of the adipogenic protein E4orf1 from adenovirus 36 through an in silico approach. Journal of Molecular Modeling, v. 26, n. 10, p. 9-pg., 2020-09-25. (19/06172-4)