S-nitrosothiols from Aryl-amide and Aryl-pyrimidin-2-ones (thiones) derivatives - potential double inhibitors of HIV-1-PR and renin: synthesis, structural analysis and biological tests

• Grant number: 13/16644-4
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2013
• End date: July 31, 2016
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Adriana Karla Cardoso Amorim Reis
• Grantee: Adriana Karla Cardoso Amorim Reis
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil
• City of the host institution: Diadema
• Associated researchers: Hugo Pequeno Monteiro

Abstract

Currently, polytherapies based on the combined utilization of reverse transcriptase and HIV protease inhibitors are the most efficient in AIDS treatment. Clinical assays clearly established the efficacy of these therapies in reducing the viral load below to its detection threshold. They also showed the therapy efficacy in recovering T CD4 cell count. However, the existence of virus reservoirs at the lymphatic system and at the central nervous system indicates that reverse transcriptase and protease inhibitors are not completely efficient. In the treatment of hypertension the renin-angiotensin-aldosterone (RAAS) plays a major role in regulating blood pressure. Inhibition of renin protease activity is a potential therapeutic strategy in the treatment of hypertension. Common structural and functional features between HIV-protease and Renin lead us to propose the design of inhibitors with double action.This research proposal involves theoretical calculations, synthesis of aryl-amides, aryl-pirimidinones, and their s-nitrosothiol derivatives. The compounds will be synthesized using environmentally sustainable techniques. Reactions will be carried out under microwave irradiation in solvent-free conditions and/or organic carbonates as solvents. NMR and IR-based analysis will be used to determine the compounds stability in addition to other physicochemical parameters. The synthesized and chemically characterized compounds will be tested as HIV-protease and Renin protease inhibitors. (AU)

Scientific publications

(6)

(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)

RODRIGUES, ALESSANDRO; OLIVATO, PAULO R.; ZUKERMAN-SCHPECTOR, JULIO; MAGANHI, STELLA H.; REIS, ADRIANA K. C. A.; TIEKINK, EDWARD R. T.. Molecular Structures of Isomeric Ortho, Meta, and Para Bromo-Substituted alpha-Methylsulfonyl-alpha-diethoxyphosphoryl Acetophenones by X-ray and DFT Molecular Orbital Calculations. Journal of Physical Chemistry A, v. 119, n. 32, p. 8714-8723, AUG 13 2015. (13/16644-4, 13/10073-5)

MONTEIRO, HUGO P.; RODRIGUES, ELAINE G.; AMORIM REIS, ADRIANA K. C.; LONGO, JR., LUIZ S.; OGATA, FERNANDO T.; MORETTI, ANA I. S.; DA COSTA, PAULO E.; TEODORO, ANA C. S.; TOLEDO, MAYTE S.; STERN, ARNOLD. Nitric oxide and interactions with reactive oxygen species in the development of melanoma, breast, and colon cancer: A redox signaling perspective. NITRIC OXIDE-BIOLOGY AND CHEMISTRY, v. 89, p. 1-13, AUG 1 2019. (16/06539-7, 13/16644-4, 12/10470-1)

ABBUD HANNA ROQUE, ANA CAROLINA; SANTOS, DANIEL DE CARVALHO; REGINATO, MARCELO MOTA; REIS, ADRIANA KARLA CARDOSO AMORIM. Conformational analysis for infrared spectroscopy and theoretical calculations of some 2-bromo-2-propyl 2-aryl-acetates, ibuprofen and naproxen analogs. Journal of Molecular Structure, v. 1233, JUN 5 2021. (13/16644-4)

REGINATO, MARCELO MOTA; PAIVA, DERISVALDO ROSA; SENSATO, FABRICIO RONIL; MONTEIRO, HUGO PEQUENO; CARDOSO AMORIM REIS, ADRIANA KARLA. Conformational study of the electronic interactions and nitric oxide release potential of new S-nitrosothiols esters derivatives of ibuprofen, naproxen and phenyl acids substituted (SNO-ESTERS): Synthesis, infrared spectroscopy analysis and theoretical calculations. SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY, v. 207, p. 132-142, JAN 15 2019. (13/16644-4)

MONTEIRO, HUGO P.; COSTA, PAULO E.; REIS, ADRIANA K. C. A.; STERN, ARNOLD. Nitric oxide: Protein tyrosine phosphorylation and protein S-nitrosylation in cancer. BIOMEDICAL JOURNAL, v. 38, n. 5, p. 380-388, SEP-OCT 2015. (10/19013-7, 13/16644-4, 12/10470-1)

SERRALBO, ALINE SILVEIRA; SANTOS, DANIEL DE CARVALHO; VIEIRA SILVEIRA, MARGHUEL APARECIDA; OKAMOTO, DEBORA NOMA; JULIANO, MARIA APARECIDA; DE VASCONCELLOS, SUZAN PANTAROTO; CARDOSO AMORIM REIS, ADRIANA KARLA. Sustainable Synthesis of Novel Arylamide L-Cysteine Methyl Esters Peptidomimetic Derivatives: Inhibitors of Serine and Cysteine-like Proteases. ORBITAL-THE ELECTRONIC JOURNAL OF CHEMISTRY, v. 12, n. 4, p. 258-266, OCT-DEC 2020. (13/16644-4)