NMR analysis, cytotoxic activity and theoretical study of a complex between SRPIN340 and p -sulfonic acid calix[6]arene.
Lívia Cristina de Souza ViolNatália Aparecida Liberto SilvaCristiane Isaac CerceauMarcus Vinícius de Andrade BarrosRaoni Pais SiqueiraVictor Hugo Sousa GonçalvesGustavo Costa BressanSergio Antonio FernandesElson Santiago AlvarengaVanessa Carla Furtado MosqueiraPublished in: Future medicinal chemistry (2024)
Aim: This study aimed to enhance the aqueous dissolution of SRPK inhibitor N -(2-(piperidin-1-yl)-5-(trifluoromethyl)phenyl)isonicotinamide (SRPIN340). Materials & Methods: A complex with p -sulfonic calix[6]arene (Host) and SRPIN340 (Guest) was prepared, studied via 1 H nuclear magnetic resonance (NMR) and theoretical calculations and biologically evaluated on cancer cell lines. Results & conclusion: The 1:1 host (H)/guest (G) complex significantly enhanced the aqueous dissolution of SRPIN340, achieving 64.8% water solubility as determined by 1 H NMR quantification analysis. The H/G complex reduced cell viability by 75% for HL60, ∼50% for Nalm6 and Jurkat, and ∼30% for B16F10 cells. It exhibited greater cytotoxicity than free SRPIN340 against Jurkat and B16F10 cells. Theoretical studies indicated hydrogen bond stabilization of the complex, suggesting broader applicability of SRPIN340 across diverse biological systems.
Keyphrases
- magnetic resonance
- induced apoptosis
- high resolution
- solid state
- cell cycle arrest
- water soluble
- magnetic resonance imaging
- ionic liquid
- papillary thyroid
- computed tomography
- endoplasmic reticulum stress
- cell death
- molecular dynamics
- signaling pathway
- molecular dynamics simulations
- density functional theory
- contrast enhanced
- monte carlo