In Silico Identification and Biological Evaluation of Antioxidant Food Components Endowed with Human Carbonic Anhydrase IX and XII Inhibition

Abstract

The tumor-associated isoenzymes <i>h</i>CA IX and <i>h</i>CA XII catalyze the hydration of carbon dioxide to bicarbonate and protons. These isoforms are highly overexpressed in many types of cancer, where they contribute to the acidification of the tumor environment, promoting tumor cell invasion and metastasis. In this work, in order to identify novel dual <i>h</i>CA IX and XII inhibitors, virtual screening techniques and biological assays were combined. A structure-based virtual screening towards <i>h</i>CA IX and XII was performed using a database of approximately 26,000 natural compounds. The best shared <i>hits</i> were submitted to a thermodynamic analysis and three promising best <i>hits</i> were identified and evaluated in terms of their <i>h</i>CA IX and XII inhibitor activity. In vitro biological assays were in line with the theoretical studies and revealed that syringin, lithospermic acid, and (-)-dehydrodiconiferyl alcohol behave as good <i>h</i>CA IX and <i>h</i>CA XII dual inhibitors.