Synthesis of New Calixarene Derivatives and Evaluation of Their Cytotoxic Activity

Abstract

Since calixarenes are more easily synthesized and functionalized than other supramolecules, they are compounds of interest in organic chemistry. In this study, the dihydrazide (3a and 3b) and diamino propyl (6a and 6b) derivatives of p-tert-butylcalix[4]arene and calix[4]arene were synthesized. Then the L-proline methyl ester substituted chlorocyclopropenium was reacted with the calix[4]arene derivatives (3a, 3b, 6a, and 6b) at room temperature in CH2Cl2 to obtain calix[4]arene superbase derivatives (4a, 4b, 7a, and 7b) in 75%, 60%, 70% and 55% yield, respectively. The synthesized compounds' structure was elucidated by using spectroscopic techniques (FTIR, 1H NMR, and 13C NMR ). The cytotoxic properties of the calix[4]arene superbase derivatives were investigated against different human cancerous cells, including A549, DLD-1, HEPG2, and PC-3, as well as human healthy epithelium cell line PNT1A. The cytotoxicity results showed that calix[4]arene superbase derivatives inhibited the proliferation of DLD-1, A549, HEPG2, and PC-3 cells in a dose-dependent manner. Compound 7a had the highest toxic effect on colorectal carcinoma (IC50: 4.7 µM), and the IC50 values were 18.5 µM and 74.4µM against human prostate and lung cancer cells, respectively. Furthermore, the compound 4b was found more effective on hepatocellular carcinoma cells (IC50: 210.2 µM). As a result, the synthesized calix[4]arene superbase derivatives can be developed to treat different human cancer cells. They can be considered as a preliminary result for molecular-level research.