Inclusion phenomenon of β-carboline alkaloids with sulfonatocalix[4]arene: Photophysical, cytotoxicity and theoretical study

Abstract

β-carbolines are nonpolar heterocyclic aromatic amines known as Harman and Norharman. Harman and Norharman, with anticancer effects, have recently attracted much attention but have experienced difficulty in their pharmacological development due to their low oral bioavailability. In this article, we describe the complexation of Harman (H) and Norharman (NH) with p-sulfonatocalix[4]arene (SCX4) as a feasible option to improve its solubility and, as a result, improve the cytotoxic effect on cell lines. Spectroscopic techniques, such as UV–visible absorption, fluorescence, FT-IR, FE-SEM, HRMS, NMR techniques, and molecular docking calculations, were used to analyze these inclusion complexes H ⊂ SCX4 and NH ⊂ SCX4. UV–visible absorption and steady-state fluorescence spectroscopy were used to investigate the interaction between Harman and Norharman with p-sulfonatocalix[4]arene (SCX4). A simple and precise HPLC-based approach has assessed the retention times of H, NH, SCX4, and its complexes. Additionally, an in vitro cytotoxicity study revealed that the synthesized complexes were not toxic to the mouse embryonic fibroblast (3 T3-L1) cell line. Therefore, the present study confirmed that the H ⊂ SCX4 and NH ⊂ SCX4 complexes are readily soluble in an aqueous medium that does not cause toxicity in the primary cell line and might provide a feasible option for increasing the solubility of these class of poorly soluble drugs.