Prashinta Nita Damayanti, Ritmaleni, Erna Prawita Setyowati
Prashinta Nita Damayanti1, Ritmaleni2*, Erna Prawita Setyowati3
1Student of Postgraduate Program, Master Program of Pharmaceutical Sciences and Technology, Faculty of Pharmacy, Gadjah Mada University, Sekip Utara, Yogyakarta 55281, Indonesia.
2Departement Of Pharmaceutical Chemistry, Faculty of Pharmacy, Gadjah Mada University, Sekip Utara, Yogyakarta 55281, Indonesia.
3Departement Of Pharmaceutical Biology, Faculty of Pharmacy, Gadjah Mada University, Sekip Utara, Yogyakarta 55281, Indonesia.
Volume - 13,
Issue - 10,
Year - 2020
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.
Cite this article:
Prashinta Nita Damayanti, Ritmaleni, Erna Prawita Setyowati. Synthesis and antibacterial activity of 4-Piperidone curcumin analogues against Gram-positive and Gram-negative bacteria. Research J. Pharm. and Tech. 2020; 13(10):4765-4769. doi: 10.5958/0974-360X.2020.00838.0
Prashinta Nita Damayanti, Ritmaleni, Erna Prawita Setyowati. Synthesis and antibacterial activity of 4-Piperidone curcumin analogues against Gram-positive and Gram-negative bacteria. Research J. Pharm. and Tech. 2020; 13(10):4765-4769. doi: 10.5958/0974-360X.2020.00838.0 Available on: https://rjptonline.org/AbstractView.aspx?PID=2020-13-10-41
1. Bezlon G., Shanmugha Sundhar D., Rinu Edwin R. E. Design and Stabilization of Natural Antibacterial Compound Allicin against Methicillin-Resistant Staphylococcus Aureus for Treatment as a Novel Antibiotic. Research J. Engineering and Tech. 2013; 4(4): 179-181
2. Fang, Z., Zheng, S., Chan, K., Yuan, W., Guo, Qi., Wu, W., et. al. Design, Synthesis and Antibacterial Evaluation of 2,4-disubstituted-6-thiophenyls-pyrimidine. Eur J. Med Chem. 2019; 161: 141-153.
3. Wu, B., Fu, S., Tang, H., Chen, K., Zhang, Q., Peng, A.-H., et.al. Design, Synthesis and Antibacterial Evaluation of Honokiol Derivatives. Bioorg. Med. Chem. Lett. 2018; 28: 834–838.
4. Changtam, C., de Koning, H.P., Ibrahim, H., Sajid, M.S., Gould, M.K., and Suksamrarn, A. Curcuminoid Analogs with Potent Activity Against Trypanosoma and Leishmania species. Eur J. Med Chem. 2010; 45: 941–956
5. Rai, D., Singh, J.K., Roy, N., and Panda, D. Curcumin inhibits FtsZ assembly: An Attractive Mechanism for Its Antibacterial Activity. Biochemical Journal. 2008; 410: 147–155.
6. Nair, S. T., R. Meghana, P. Shlini. Antimicrobial Activity of The Protein Fraction Obtained in The Extraction of Curcumin. Asian J. Research Chem. 2019; 12(4): 199-202
7. Sharma, R.A., Gescher, A.J., and Steward, W.P. Curcumin: The story so far. European Journal of Cancer. 2005: 41: 1955–1968.
8. P. Venugopalan, T. V. Deepthi. Chemical and Pharmacological Studies on Curcuminoids. Asian J. Research Chem. 2014; 7(3): 355-365
9. Sardjiman, S.S., Reksohadiprodjo, M.S., Hakim, L., Van der Goot, H., and Timmerman, H. 1,5-Diphenyl-1,4-pentadiene-3-ones and cyclic analogues as antioxidative agents. Synthesis and Structure-Activity Relationship. Eur J. Med Chem. 1997: 32: 625–630.
10. Rao, T.S., Vikram, BS., and Akamma, HG. Synthesis and In Vitro Antibacterial Activity Studies of Some Substituted Aryloxy-4-Thiazolidinones. Asian J. Research Chem. 2009; 2(3): 349-352
11. SD Sawant., R. N. Patil, A. A. Baravkar. Synthesis and Biological Evaluation of 1-Naphthyl and 4-Byphenyl Derivatives of 2,4,5-Trisubtituted-1H-Imidazoles as Antibacterial and Antifungal Agents. Asian J. Research Chem. 2011; 4(3): 423-428
12. M. Srinivas, Prasad, R., Chandrashekaran, S. Microwaved Assisted Synthesis and Antibacterial Activity of Some Bicyclic Pyrrolidines. Asian J. Research Chem. 2009; 2(3): 357-359
13. Kolarević, S., Milovanović, D., Avdović, M., Oalđe, M., Kostić, J., Sunjog, K., et.al. Optimisation оf the Microdilution Method for Detection of Minimum Inhibitory Concentration Values in Selected Bacteria. Botanica Serbia. 2016; 40: 29–36.
14. Divekar, K., Swamy, S., Murugan, KNV., and Devgun, M. Synthesis and Evaluation of Some New Pyrazole Derivatives as Antimicrobial Agents. Research J. Pharm. And Tech. 2010; 3(4): 1039-1043
15. Prasad, Y.R., Kumar, P.R., Deepti, Ch. A., and Ramana, M.V. Synthesis and Antimicrobial Activity of Some Novel Chalcones of 2-Hydroxy -1-Acetonapthone and 3-Acetyl Coumarin. E-Journal of Chemistry. 2006; 3: 236–241.
16. Warren, Stuart. Organic synthesis: the disconnection approach, John Wiley and Sons. Chicester. 2008
17. Purwanggana, A., Mumpuni, E., and Mulatsari, E. In Vitro and In Silico Antibacterial Activity of 1.5-bis(3’-ethoxy-4’-hydroxyphenyl)-1-4-pentadiene-3-One. Int. J. Pharm Pharm Sci. 2018; 10(5):70-76
18. Pavia, D.L., Lampman, G.M., and Kriz, G.S. Introduction to Spectroscopy: A Guide for Students of Organic Chemistry, Harcourt College Publishers. Philadelphia. 1979
19. Lagisetty, P., Powell, D. R., and Awasthi, V. Synthesis and Structural Determination of 3,5-bis(2-fluorobenzylidene)-4-piperidone Analogs of Curcumin. Journal of Molecular Structure. 2010; 936: 23-28.
20. Hamzah, H., Pratiwi, S. U. T., and Hertiani, T. Efficacy of Thymol and Eugenol Against Polymicrobial Biofilm. Indones. J. Pharm. 2018; 4: 214-221
21. Vicini, P., Geronikaki, A., Anastasia, K., Incerti, M., and Zani, F. Synthesis and Antimicrobial Activity of Novel 2-thiazolymino-5-arylidene-4-thiazolidinones. Bioorg. Med. Chem. Lett. 2006; 14: 3859-3864
22. Aruneswari, U., Rani, S. U., Devi, M. A., Rajitha, G. Synthesis and Evaluation of Subtituted Imidazolones for Antibacterial and Antioxidant Activities. Asian J. Research Chem. 2011; 4(2): 257-259
23. Patel, VI., Patel, RG., Patel, NG., Panchal, SR., and Bhardia, PD. Synthesis and Study of Some New 2-Imino-3-[Carboxamido o-hydroxyphenyl]-5-Arylidene-4-Thiazolidinone as Antibacterial Agents. Asian J. Research Chem. 2010; 3(2): 468-471
24. Shukla, K. S., Pandey, S., and Chawla, P. Synthesis of Some 5-(substituted benzylidene-2, 4-dioxothiazolidin-3-yl) Benzoic Acid Derivatives by Conventional and Microwave Assisted Methods and Evaluation of Their Potential as Antimicrobial Agents. Anti-infective Agents. 2019; 17(2): 115-129
25. Murtada Ahmed Oshi. Evaluation of Antibacterial Activities and Formulation of Black Mahlab Seeds Aqueous Extract. Research J. Pharma. Dosage Forms and Tech. 2013; 5(2): 99-106
26. Hindi, N.K.K., Abdul-Husin, I.F., Al-Mahdi, Z.K.A., et al. Effectiveness of Aqueous Extract of Green, Black and Red Tea Leaves against some Types of Gram positive and negative Bacteria. Research J. Pharm. And Tech. 2017; 10(6): 1957-1962
27. Nikaido, H. Prevention of Drug Access to Bacterial Targets: Permeability Barriers and Active Efflux. Science. 1994; 264:382-388