Glycosyl Isoxazoles for Targeting of Tumor Microenvironment and Cancer Cells: Highly Selective Inhibitors of Carbonic Anhydrases IX and XII Showing Cytotoxic Activity

LE PORS, MACARENA S.; SANTA MARIA DE LA PARRA, LUCÍA; RIAFRECHA, LEONARDO E.; VULLO, DANIELA; LEÓN, IGNACIO E.; SUPURAN, CLAUDIU T.; COLINAS, PEDRO A.

ChemistrySelect

Wiley

Año: 2023 vol. 8

2365-6549

We report the synthesis of twelve novel O-glycosylmethylisoxazoles incorporating the phenoxyaryl moiety, that weredesigned to selectively target the cancer-related humancarbonic anhydrase (CA, EC 4.2.1.1) isoforms. The O-glycosideshave been prepared by cycloaddition of nitrile oxides to Opropargylglycosides. Compounds were assessed as inhibitorsof the physiologically dominant isozymes hCA I and II and thetumor-associated isozyme hCA IX and hCA XII. In this study,several glycosides have been identified as highly selectiveinhibitors of hCA IX and XII. Glycoconjugation enhances theanticancer activity against human osteosarcoma cell line. Thus,these glycosides may prove interesting lead candidates for atargeted cancer therapy.