Curcumin mimics of potential chemoprevention with NQO1 induction properties

Chemoprevention is one of the accessible strategies for preventing, delaying or reversing cancer processing utilizing chemical intervention of carcinogenesis. NAD(P)H quinone oxidoreductase 1 (NQO1) is a xenobiotic metabolizing cytosolic enzyme/protein with important functional properties towards oxidation stress, supporting its ability in detoxification/chemoprotective role. A set of 3,5-diylidene-4-piperidones (as curcumin mimics) bearing alkyl sulfonyl group were synthesized with potential NQO1 induction properties. Compounds 5ab (R = 2-MeOC₆H₄, R' = Me) and 5ac (R = 2-MeOC₆H₄, R' = Et) are the most promising agents synthesized (% induction of NQO1 = 51.562, 45.793) relative to that of 4'-bromoflavone (4'-BF, reference standard) at 10 µM. LPS-induced iNOS production in RAW264.7 macrophages of the most promising agents discovered (5ab and 5ac) displayed concentration-dependent with comparable activities to the reference anti-inflammatory drug indomethacin. Molecular modeling studies (including QSAR, molecular docking and molecular dynamics) were accessed supporting the observed biological profiles.