Host-Guest Complexation of Oxaliplatin and Para-Sulfonatocalix[n]Arenes for Potential Use in Cancer Therapy

Abstract

P-sulfonatocalix[n]arenes have demonstrated a great potential for encapsulation of therapeutic drugs via host-guest complexation to improve solubility, stability, and bioavailability of encapsulated drugs. In this work, guest-host complexes of a third-generation anticancer drug (oxaliplatin) and p-4-sulfocalix[n]arenes (n = 4 and 6; p-SC4 and p-SC6, respectively) were prepared and investigated, using 1H NMR, UV, Job’s plot analysis, and DFT calculations, for use as cancer therapeutics. The peak amplitude of the prepared host-guest complexes was linearly proportional to the concentration of oxaliplatin in the range of 1.0 × 10−5 M−1 to 2.1 × 10−4 M−1. The reaction stoichiometry between either p-SC4 or p-SC6 and oxaliplatin in the formed complexes was 1:1. The stability constants for the complexes were 5.07 × 104 M−1 and 6.3 × 104 M−1. These correspond to complexation free energy of −6.39 and −6.52 kcal/mol for p-SC4 and p-SC6, respectively. Complexation between oxaliplatin and p-SC4 or p-SC6 was found to involve hydrogen bonds. Both complexes exhibited enhanced biological and high cytotoxic activities against HT-29 colorectal cells and MCF-7 breast adenocarcinoma compared to free oxaliplatin, which warrants further investigation for cancer therapy.

Betaine host–guest complexation with a calixarene receptor: enhanced in vitro anticancer effect

“…Previous studies reported the direct relationship between the degree of the chemical shi of a guest molecule's protons and their depth of penetration inside the hollow cavity of the host molecule, designating the formation of host-guest inclusion complexes. 28,29,41,42 The most signicant upeld shi of $0.58 ppm was observed for the protons of the methyl groups bonded to the quaternary ammonium head of betaine, H c (Table 1 and Fig. S1 †) showing that they possessed the most signicant shielding effect.…”

“…The cell viability of either cancerous or non-cancerous cells was examined employing the SRB assay, and the IC 50 (in mg mL À1 ) was calculated using our methods described previously. 28,29,[32][33][34]…”

“…The formation of host-guest inclusion complexes between betaine and p-SC4, was investigated using UV-Vis spectroscopy. [27][28][29] The UV absorbance spectra of 0.2 mM betaine, 0.2 mM p-SC4, and a mixture comprising a mixture of 0.2 mM of each of betaine and p-SC4 in deionized water are presented in Fig. 1.…”

“…25,26 Many studies reported the possible use of supramolecular structures as hosts for different antineoplastic drugs to enhance their water solubility, chemical stability and improve their selective uptake into tumor cells. [26][27][28][29] Particularly, calix[n]arenes (n ¼ 4, 6, and 8) signify a crucial class of macrocycles that have been widely utilized in drug delivery. Calixarenes are ideal host molecules formed of phenolic units linked by methylene bridges comprising an upper rim with para-substituent of a phenolic ring, a lower rim with a phenolic hydroxyl group, and a hydrophobic p electron-rich core cavity.…”

“…This unique structure of calix[n]arenes permits their facile functionalization using sulfonate groups via their phenolic rings' para-position, forming the water-soluble derivative (>0.1 mol L À1 ), parasulfonatocalix[n]arenes. [26][27][28][29] para-Sulfonatocalix[n]arenes are nontoxic to human cells at in vivo doses up to 10 3 mg kg À1 . Furthermore, in aqueous media, para-sulfonatocalix[n]arenes demonstrated an ability to host different guest molecules in their cavities via inclusion complexation.…”