Novel Curcuminoid Analogues as Bioactive Agents
Assist. Prof. Dr. Vachiraporn Ajavakom
Department of Chemistry, Faculty of Science, Ramkhamhaeng University
A novel tetrahydrocurcumin (THC) analogues, which are tetrahydrocurcumin-dihydropyrimidinone (THC-DHPM) and tetrahydrocurcumin-dihydropyridine (THC-DHP), have been successfully synthesized by multi-component Biginelli and Hantzsch reactions, respectively. Conceptually, 1,3-dicarbonyl moiety of THC, can be applied in these cyclocondensation reactions. THC-DHPMs were prepared in good to excellent yields by treatment of THC, aromatic aldehyde and urea with catalytic amount of copper sulphate. Hantzsch reaction was utilized to construct THC-DHP from THC, aromatic aldehyde, and ammonium acetate. The formation of THC-DHP occurred in the presence of p-toluenesulfonic acid (p-TSA) and 4 Å molecular sieves as dehydrating reagent. The evaluation of acetylcholinesterase inhibitors of THC-DHPMs showed that they exhibited higher inhibitory activity than their parent analogues. THBDC-DHPM demonstrated the most potent inhibitory activity with an IC50 value of 1.34 ± 0.03 µM which was more active than the approved drug galanthamine (IC50= 1.45 ± 0.04 µM). THC-DHPs were assessed for cytotoxicity activity against three cancer cell lines (HeLa, HT29 and MCF7). THC-DHP analogue containing 4-0CH3 phenyl group displayed better result against HT29 (IC50= 7.71 µM) with IC50 value as active as that of the reference drug doxorubicin (IC50. = 7.30 µM).