Synthesis and antibacterial activity of 4-piperidone curcumin analogues against gram-positive and gram-negative bacteria

The rapid development of antibiotics resistance makes antibiotics become less effective for the treatment of bacterial infections. Accordingly, it is so important to discovery and development of new antibacterial agents. Three 4-piperidone curcumin analogues (3,5-bis-(2-chlorobenzylidene)-4-piperidone (1), 3,5-bis-(4-chlorobenzylidene)-4-piperidone (2) and 3,5-bis-(2,4-dichlorobenzylidene)-4-piperidone (3) were synthesized from 4-piperidone monohydrate hydrochloride with 2-chlorobenzaldehyde, 4-chlorobenzaldehyde and 2,4-dichlorobenzaldehyde. The Claisen-Schmidt condensation reaction was used in acid condition. All the compounds showed light yellow crystal with percentage of yield 39, 41 and 34 respectively. All the structure compounds were confirmed by using IR,¹H-NMR,¹³C-NMR, and MS. The evaluation of antibacterial activity conducted by Agar diffusion method against Gram-positive bacteria such as Bacillus subtilis (ATCC 6633) and Enterococcus faecalis (ATCC 29212), and Gram-negative bacteria such as Escherichia coli (ATCC 25922), and Pseudomonas aeruginosa (ATCC 27853). The result showed that all the compounds showed significant activity but they were more effective against Gram-positive bacteria as compared to their Gram-negative counterparts. Analogues curcumin compound showed that there was antibacterial activity up to concentration 62,5 μg/mL on Gram positive bacteria and 125 μg/mL on Gram negative bacteria. The compound 3,5-bis-(2,4-dichlorobenzylidene)-4-piperidone (3) containing two substituent-Cl on ortho and para position in the benzene ring has best activity than compound 1 and 2.