In a recent study performed by Gandhy et al., it was reported that curcumin (Curc) mono-carbonyl analogs containing a piperidone core (Boc piperidone chalcones) in its chemical structure, displayed potent anticancer activity against colon cancer cells at IC50 = 0.7 µM. This interesting finding inspired us to perform the first total synthesis of several chalcones containing tert-butoxycarbonyl (Boc) piperidone core. Through a three-step synthetic route, 6 analogs were successfully synthesized for a structure-activity relationship (SAR) study involving both LoVo and COLO-205 cells. The synthesis of Boc-piperidone chalcones started with the protection of a phenolic benzaldehyde with tetrahydropyranyl protecting group. An Aldolic reaction between the tetrahydropyranyl protected phenolic benzaldehyde and Boc-piperidone using lithium hydroxide and subsequent removal of the tetrahydropyranyl protecting group afforded the desired Boc-piperidone chalcones in 55-97% yield. We gathered preliminary results that showed that Boc-piperidone chalcones were cytotoxic against LoVo cells at IC50 values that range from 3.51-170.87 µg/mL and displayed toxic activity against highly metastatic prostate cancer cell lines 22RV1 and PC3 at IC50 of 17.1 µg/mL and 22.9 µg/mL, respectively. In addition, our preliminary data showed that Boc-piperidone chalcones inhibited the relaxing activity of human DNA topoisomerase I (molecular target of some anticancer compounds) at 100 µg/mL, which strongly support the potential of Boc-piperodone chalcones as anticancer agents. Results of our study will impact broadly the field by developing new generation of Boc-piperidone chalcones with improved anticancer activity against both colorectal and prostate cancer cells.

Syntheses of 4-bocpiperidone chalcones and their potential as anticancer agents

255th National Meeting (2018)

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