Novel non-cyclooxygenase inhibitory derivatives of naproxen for colorectal cancer chemoprevention.

ABSTRACT: A structure-based medicinal chemistry strategy was applied to design new naproxen derivatives that show growth inhibitory activity against human colon tumor cells through a cyclooxygenase (COX)-independent mechanism. In vitro testing of the synthesized compounds against the human HT-29 colon tumor cell line revealed enhanced growth inhibitory activity compared to the parent naproxen with 3a showing IC₅₀ of 11.4 μM (two orders of magnitude more potent than naproxen). Selectivity of 3a was investigated against a panel of three tumor and one normal colon cell lines and showed up to six times less toxicity against normal colonocytes. Compound 3a was shown to induce dose-dependent apoptosis of HT116 colon tumor cells as evidenced by measuring the activity of casp

SUBMITTER: Aboul-Fadl T 

PROVIDER: S-EPMC4993210 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature