Formation of the inclusion complex of water soluble fluorescent calix[4]arene and naringenin: solubility, cytotoxic effect and molecular modeling studies

Abstract

Naringenin is considered as an important flavonoid in phytochemistry because of its important effect on cancer chemoprevention. Unfortunately its poor solubility has restricted its therapeutic applications. In this study, an efficient water-soluble fluorescent calix[4]arene (compound 5) was synthesized as host macromolecule to increase solubility and cytotoxicity in cancer cells of water-insoluble naringenin as well as to clarify localization of naringenin into the cells. Complex formed by host–guest interaction between compound 5 and naringenin was analyzed with UV–visible, fluorescence, FTIR spectroscopic techniques and molecular modeling studies. Stern–Volmer analysis showed binding constant value of K<inf>sv</inf> 3.5 × 107 M−1 suggesting strong interaction between host and guest. Binding capacity shows 77% of naringenin was loaded on compound 5. Anticarcinogenic effects of naringenin complex were evaluated on human colorectal carcinoma cells (DLD-1) and it was found that 5-naringenin complex inhibits proliferation of DLD-1 cells 3.4-fold more compared to free naringenin. Fluorescence imaging studies show 5-naringenin complex was accumulated into the cytoplasm instead of the nucleus. Increased solubility and cytotoxicity of naringenin with fluorescent calix[4]arene makes it one of the potential candidates as a therapeutic enhancer. For deep understanding of host–guest interaction mechanisms, complementary multiscale molecular modeling studies were also carried out. Communicated by Ramaswamy H. Sarma. © 2020 Elsevier B.V., All rights reserved.