Curcuminoids versus Pyrazole‐Modified Analogues: Synthesis and Cytotoxicity against HepG2 Cancer Cell Line

Abstract Twenty compounds including curcuminoids and their pyrazole‐modified analogues were synthesized in a two‐step reaction: (i) condensation between benzaldehyde derivatives and pentane‐2,4‐dione and (ii) pyrazole cyclization of the 1,3‐diketone group in the resulting curcuminoids with hydrazine hydrate. The synthesized compounds were assayed for in vitro anticancer activity against HepG2 cancer cell line by determining their half‐maximal inhibitory concentration (IC 50 ). Pyrazole curcuminoid ( 1 a , IC 50 =1.53±0.11 μM) was found to be the most potent molecule against the cancer cells. The pyrazole curcuminoids ( 1 a – 3 a , 5 a ) significantly exhibited between 2‐ to 23‐fold higher anticancer activities when compared with their parent structures ( 1 – 3 , 5 ). However, the class of fluorinated analogues ( 7 – 10 ; 7 a – 10 a ) displayed inactivities or activities close to those of respecting compounds ( 1 – 6 ; 1 a – 6 a ). Structure‐activity relationship analysis indicated that the phenolic motif is responsible for inhibition of cell growth whereas the fluoro/methoxy substituents on the aromatic rings have insignificant contributions to inhibitory activities against HepG2.