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Molecules ; 25(24)2020 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-33327642

RESUMO

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.


Assuntos
Antineoplásicos/síntese química , Sulfonatos de Arila/síntese química , Calixarenos/síntese química , Composição de Medicamentos/métodos , Oxaliplatina/farmacologia , Antineoplásicos/metabolismo , Sulfonatos de Arila/metabolismo , Calixarenos/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células HT29 , Humanos , Ligação de Hidrogênio , Concentração Inibidora 50 , Cinética , Células MCF-7 , Modelos Químicos , Oxaliplatina/metabolismo , Teoria Quântica , Termodinâmica
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