Unveiling the versatility of novel oxacalix[4]arene platform: Systematic screening and comparative study on biological and antioxidant potency

Abstract

Calixarene, a third generation supramolecule, have made their signature in biomedical applications through their unique physicochemical characteristics. Oxacalixarene, a class of heteracalixarene, is less explored in this respect though it has manifested its potentiality in earlier very few reports. Here we are reporting for the first time a systematic and comparative study of biological activities of different oxacalix[4]arene(OC) systems. For this purpose, very common functional groups that are available in biomacromolecules like phenolic OH (DHOC), amine (DNOC), ester (DEOC) and amide (DAOC) have been considered for functionalization to basic OC platform and the newly synthesized compounds are characterized with state-of-the-art spectroscopic techniques. Analysis of DNA cleavage, DNA binding, cell cytotoxicity and antioxidant activity studies nicely define the diversity of OC in DNA protection or DNA damage phenomena. DHOC is able to protect oxidative cleavage of DNA up to 47 % against Fenton reagents. The order of binding constant (∼105) is observed in the following order: DHOC (phenolic OH) > DNOC (amine) > DAOC (amide). The article also reports the antioxidant activity of oxacalix[4]arene compounds for the first time, observed by DPPH inhibition assay. All the compounds possess antioxidant activities. Among those, DHOC shows maximum antioxidant activity, comparable to standard antioxidant ascorbic acid at 100 µM (DPPH: 60 µM). Indeed, the observed structure-function relationship of OC systems can be tailored in the future to design molecules that are specifically targeted for biomedical applications.