Experimental and computational characterization of p-Sulfocalix[4]arene mediated delivery system for morin hydrate

• Published in: Medicine in drug discovery 2024-06, Vol.22, p.100180, Article 100180
• Main Authors: Chaurasiya, Sunaina, Solanki, Raghu, Athar, Mohd, Jangid, Ashok Kumar, Patel, Sunita, Jha, Prakash C., Pooja, Deep, Kulhari, Hitesh
• Format: Article
• Language: English
• Subjects: Anticancer; MH-SCA complex; Morin hydrate; Potential of Mean Force (PMF)
• ISSN: 2590-0986; 2590-0986
• DOI: 10.1016/j.medidd.2024.100180

[Display omitted] •A complex of morin hydrate [MH] and SC[4]A was prepared by solvent evaporation method.•MH-SC[4]A complex was characterized by FTIR, NMR, DLS, TEM, and DSC techniques.•MH-SC[4]A complex a showed concentration based solubility, rapid dissolution and good stability.•MH-SC[4]A complex showed time- and dose-dependent cytotoxicities to the cancer cells.•Computational data showed the complex could be used as promising drug delivery carrier. Calix[n]arene is a class of macrocyclic compounds and has been investigated to improve the physicochemical properties of water insoluble molecules. In this work, a complex of morin hydrate (MH) drug was prepared using p-sulfocalix[4]arene (SC[4]A) as complexing agent to increase its water solubility, dissolution rate and stability. Solvent evaporation methanol was used to prepare the inclusion complex (MH-SC[4]A) between pure MH and SC[4]A and analysed by FTIR, NMR, UV, DLS, TEM, and DSC techniques. Concentration-dependent solubility study showed 22 folds enhancement of MH at 8 mM concentration of SC[4]A. The in vitro anticancer efficacy of MH against A549 cells was increased after complex formation. AO/EtBr staining study showed the more apoptosis mediated anticancer activity than native MH. Molecular geometry, stabilizing interactions, release behaviour and full-unwinding pathway of the complex were characterized by the computed Potential of Mean Force (PMF) using extended umbrella sampling. The combined computational and experimental data confirmed that our designed MH-SC[4]A complex could be utilized as a promising drug delivery carrier for hydrophobic MH.