A rapid synthesis of lavendustin-mimetic small molecules by click fragment assembly

Lavendustin-mimetic small molecules modifying the linker –CH2–NH– with an 1,2,3-triazole ring have been synthesized via a click chemistry. Two pharmacophoric fragments of lavendustin were varied to investigate chemical space and the auxophoric –CH2–NH– was altered to an 1,2,3-triazole for rapid click conjugation. The small molecules were evaluated against HCT116 colon cancer and CCRF-CEM leukemia cell lines. Among 28 analogues, 3-phenylpropyl ester 26b inhibited CCRF-CEM leukemia cell growth with GI50 value of 0.9 μM.

A lavendustin-mimetic small-molecule library has been synthesized via a click chemistry. 3-Phenylpropyl ester 26b inhibited CCRF-CEM leukemia cell growth with GI50 value of 0.9 μM.Figure optionsDownload as PowerPoint slide