C5-Modified nucleosides exhibiting anticancer activity

We describe (i) a simple method for the synthesis of C5-modified nucleosides from 5-iodo-2′-deoxyuridine and (ii) their activity against six types of human cancer cell lines (HCT15, MM231, NCI-H23, NUGC-3, PC-3, ACHN). We generated nitrile oxides in situ from oximes using a commercial bleaching agent; their cycloadditions with 5-ethynyl-2′-deoxyuridine yielded isoxazole derivatives possessing activity against the cancer cell lines. We synthesized several azides from benzylic bromides and their click reactions with 5-ethynyl-2′-deoxyuridine provided triazole derivatives.

C5-Modified nucleosides with anticancer activity were designed and synthesized by [3+2] cycloaddition. The nucleosides were tested against six different cancer cell lines. The triazole nucleosides which we synthesized through click chemistry exhibit much lower toxicity unlike their isoxazole congeners.Figure optionsDownload as PowerPoint slide