Banca de QUALIFICAÇÃO: JAMERSON WESLEY SILVA

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : JAMERSON WESLEY SILVA
DATE: 21/09/2026
TIME: 14:00
LOCAL: Plataforma RNP
TITLE:

SYNTHESIS AND EVALUATION OF THE POTENTIAL PHARMACOLOGICAL ACTIVITY OF AMINOQUINOLINE
COMPOUNDS HYBRIDIZED WITH NON-STEROIDAL ANTI-INFLAMMATORY DRUGS

KEY WORDS:

4-Aminoquinolines; Hybrid molecules; Non-steroidal anti-inflammatory drugs; Molecular docking; Biological assays.

PAGES: 104
BIG AREA: Ciências Exatas e da Terra
AREA: Química
SUMMARY:

This study reports the rational design, synthesis, spectroscopic characterization, and anti-inflammatory evaluation of novel 4-aminoquinoline derivatives (n=2, 3) and their corresponding hybrid molecules coupled with Non-Steroidal Anti-inflammatory Drugs (NSAIDs: Ibuprofen and Naproxen). The in silico computational strategy integrated semi-empirical quantum calculations (PM6), pharmacokinetic screening (SwissADME / BOILED-Egg), hepatic metabolic stability prediction (BioTransformer 3.0), and molecular docking into the active site of the COX-2 enzyme (AutoDock 4.2.6; PDB: 1CX2). In silico simulations revealed that the hybrids possess high passive gastrointestinal absorption and a bicentric binding mode within COX-2, achieving predicted inhibition constants (Ki) in the nanomolar range (e.g., ICEQ: ΔG = -11.5 kcal/mol, Ki = 3.55 nM). The synthetic route comprised nucleophilic aromatic substitution (SNAr) reactions to yield aminoquinoline precursors (CEQ, DAPQ, PCQ, and DAQ), followed by a one-pot amide coupling mediated by SOCl2/Et3N, affording the hybrids ICEQ, NCEQ, IDAPQ, and NDAPQ in 22% to 40% yields. Structural elucidation via 1H-NMR and FTIR confirmed amide bond formation by the shift of the C=O stretching band to 1641 cm−1 and the emergence of amidic NH signals at δ 6.0 - 6.3 ppm. Thermal analyses (TGA/DSC) indicated thermal stability up to 160 - 210 °C (melting points) and oxidative decomposition above 450 °C. In biological assays using LPS/IFN-γ-stimulated J774 macrophages, DAPQ and IDAPQ showed superior maximum efficacy in inhibiting nitric oxide production (Emax = 78.8% and 71.5%, respectively) compared to reference drugs Chloroquine (53.3%) and Ibuprofen (61.2%). The NDAPQ hybrid exhibited potent NO inhibition (Emax = 76.7%) at a low concentration (6.25 μM), outperforming Naproxen in potency at reduced doses. These findings validate molecular hybridization as a promising strategy for the development of new anti-inflammatory drug prototypes.

COMMITTEE MEMBERS:
Externo(a) à Instituição - GERALDO JOSÉ DA SILVA NETO
Interno(a) - 2343745 - JULIO COSME SANTOS DA SILVA
Presidente - 1348288 - MARIO ROBERTO MENEGHETTI