Synthesis and Molecular Docking Study of 1-(3-Chloropropyl)-3,5-Bis((E)-4-Methoxybenzylidene)Piperidin-4-One as Dengue Virus Type 2 (DEN2) NS2B/NS3 Protease Inhibitor Candidate

Romi Habibi (Department of Chemistry, University of Riau)
Noval Herfindo (Chemistry Department, University of Riau)
Rudi Hendra (Chemistry Department, University of Riau)
Hilwan Y. Teruna (Chemistry Department, University of Riau)
Adel Zamri (Chemistry Department, University of Riau)

Pharmacology and Clinical Pharmacy Research
Vol 5, No 1

Curcumin is a secondary metabolite compound that has diverse biological activities. However, it is easily hydrolyzed at physiological pH due to the presence of the β-diketone group. Therefore, the replacement of the β-diketone group with mono ketone is expected to overcome this issue. We hereby report the synthesis of mono ketone curcumin derivatives from piperidone by two-steps reactions. The synthesis of curcumin derivate 3 was carried out by Claisen-Schmidt condensation between 4-piperidone and 4-methoxybenzaldehyde using alkaline catalyst. The synthesized curcumin derivate 3 was then reacted with the 1-bromo-3-chloropropane to produce curcumin derivate 5, 1-(3-chloropropyl)-3.5-bis((E)-4-methoxybenzylidene)piperidin-4-one, with 72% yield. The calculated docking scores, the curcumin derivate 5 possessed a better affinity for receptors than the standard panduratin A. The curcumin derivate 5 has a lower docking score of -6.40 kcal/mol compared to panduratin A with value of -5.18 kcal/mol and also had strong binding interactions to DEN2 NS2B/NS3 protease. Thus, this compound is promising candidate as a new anti-dengue agent.