Synthesis and Preliminary In Vitro Anti-inflammatory Evaluation of Mannich Bases Derivatives of 4’-Methoxy-substituted of Asymmetrical Cyclovalone Analogs

Nur Rahmawati, Hariyanti Hariyanti, Fadlina Chany Saputri, Hayun Hayun


Two of Mannich bases derivatives of 4’-methoxy-substituted of asymmetrical cyclovalone analog (ACA) (2a and 2b) were synthesized. The synthesized compounds and the other two Mannich bases derivatives of 4'-methoxy-substituted ACA (2c and 2d) were evaluated for their in-vitro anti-inflammatory activity preliminary by protein denaturation inhibition method using a final concentration of 1.57 μM. The study found that all the Mannich bases exhibited anti-inflammatory potential with inhibition ranging from 33.17- 42.47%. The activity of 2b (42,47%) and 2d (41.90%) was higher than that of diclofenac sodium (35.27%) and the parent compound 1 (38.16%). As a conclusion,  2b and 2d have a prospect as a potential candidate for an anti-inflammatory agent. Further study should be done using more specific methods.


Mannich bases derivatives, Asymmetrical, Cyclovalone, synthesis, in-vitro anti-inflammatory, protein denaturation.

Full Text:



Aluwi MFMF, Rullah K, Yamin BM, Leong SW, Bahari MNA, Lim SJ, Lam KW. 2016. Synthesis of unsymmetrical monocarbonyl curcumin analogues with potent inhibition on prostaglandin E2 production in LPS induced murine and human macrophages cell lines. Bioorg Med Chem Let. 26(10):2531-2538.

Anand P, Thomas SG, Kunnumakkara AB, Sundaram C, Harikumar KB, Sung B, Tharakan ST, Misra K, Priyadarsini IK, Rajasekharan KN, Aggarwal BB. 2008. Biological activities of curcumin and its analogues (congeners) made by man and mother nature. Biochem Pharmacol. 76:1590-1611.

Chandra S., Chatterjee P, Dey P, Bhattacharya S. 2012. Evaluation of in vitro anti-inflammatory activity of coffee against the denaturation of protein. Asian Pac J Trop Biomed. 2:S178-S180.

Gunathilake KDPP., Ranaweera KKDS., Rupasinghe HPV. 2018. In Vitro Anti-Inflammatory Properties of Selected Green Leafy Vegetables. Biomedicines 6, 107.

Guzik TJ., Korbut R., Adamek-Guzik T. 2003. Nitric oxide and superoxide in inflammation and immune regulation. J Physiol Pharmacol. 54(4):469-487.

Hayun H., Maggadani BP., Kurnia A., Hanifah A., Yuliandi M., Fitriyani I., Hadrianti SP. 2019. Anti-Inflammatory And Antioxidant Activity Of Synthesized Mannich Base Derivatives of (2E,6E)-2-[(4-Hydroxy-3-methoxyphenyl)methyl-idene]-6-(phenylmethylidene)cyclohexan-1-one. Int J App Pharm. 11 (Special Issue1):246-250.

Hayun H, Jatmika C, Purwati EM, Salim S, Kurniawan R, Chandra EG, et al. 2017. Synthesis and Free Radical-scavenging Activities of Di-Mannich Bases of Cyclovalone Derivatives. Orient J Chem. 33(6):2742-57.

Hayun H, Arrahman A, Purwati EM, Yanuar A, Fortunata F, Suhargo F, et al. 2018. Synthesis, anti-inflammatory, and antioxidant activity of Mannich bases of dehydrozingerone derivatives. J Young Pharm.10:s6-10:56-60.

Jagtap VA, Agasimundim YS, Jayachandran E, Sathe BS. 2011. In vitro anti-inflammatory activity of 2-amino-3-(substituted benzylidinecarbohydrazide)-4,5,6,7- tetrahydrobenzothiophenes. J Pharm Res. 4(2):378-9.

Lamperti M, Maspero A, Tonnesen HH, Bondani M, Nardo L. 2014. Elucidation of the relationships between H-bonding patterns and excited state dynamics in cyclovalone. Molecules. 19(9):13282-13304.

Liang G., Xiaokun Li, Li Chen, Shulin Yang, Xudong Wu, Elaine Studer, Emily Gurley, Phillip B. Hylemon, Faqing Ye, Yueru Li, and Huiping Zhou. 2008. Synthesis and anti-inflammatory activities of mono-carbonyl analogues of curcumin. Bioorg Med Chem Lett. 18(4): 1525–1529.

Prasad S, Tyagi AK, Aggarwal BB. 2014. Recent developments in delivery, bioavailability, absorption and metabolism of curcumin: the golden pigment from golden spice. Cancer Res Treat. 46(1):2–18.

Prasetyaningrum PW, Bahtiar A, Hayun H. 2018. Synthesis and cytotoxicity evaluation of novel asymmetrical mono-carbonyl analogs of curcumin (AMACs) against Vero, HeLa, and MCF7 Cell Lines. Sci Pharm. 86(2):25.

Putri TN, Bachtiar A, Hayun H. 2018. Synthesis, antioxidant, and antiinflammatory activity of morpholine Mannich base of AMACs ((2E,6E)-2-({4-hydroxy-3-[morpholin-4-yl)methyl] phenyl}methylidene)(phenylmethylidene)cyclohexan-1-one) and its analogs. J App Pharm Sci. 8:19-25.

Silverstein RM, Webster FX, Kiemle DJ. 2014.Spectrometric Identification of Organic Compounds. 7th ed. New York, USA: John Wiley and Sons, Inc.

Umapathy E, Ndebia EJ, Meeme A, Adam B, Menziwa P, Nkeh-Chungag BN, et al. 2010. An experimental evaluation of Albuca setosa aqueous extract on membrane stabilization, protein denaturation and white blood cell migration during acute inflammation. J Med Plants Res. 4:789-795.

Wang YJ, Pan M.H, Cheng AL, Lin LI, Ho YS, Hsieh CY, Lin JK. 1997. Stability of curcumin in buffer solutions and characterization of its degradation products. J Pharm Biomed Anal. 1997; 15:1867-1876.

Zhao C, Liu Z, Liang G. 2013. Promising curcumin-based drug design: Mono-carbonyl analogues of curcumin (MACs). Curr Pharm Des. 19:2114-2135. 10.2174/1381612811319110012

Zhao C., Zhang Y., Zou P., Jian Wang J., He W., Shi D., Li H., Liang G., Yang S. 2015. Synthesis and biological evaluation of a novel class of curcumin analogs as anti-inflammatory agents for prevention and treatment of sepsis in mouse model. Drug Des Dev Ther. 9:1663–1678.

Zhang Y, Zhao L, Wu J, Jiang X, Dong L, Xu F, Zou P, Dai Y, Shan X, Yang S, Liang G. 2014a. Synthesis and evaluation of a series of novel asymmetrical curcumin analogs for the treatment of inflammation. Molecules. 19:7287-7307.

Zhang Y, Jiang X, Peng K, Chen C, Fu L, Wang Z, Feng J, Liu Z, Zhang H, Liang G, Pan Z. 2014b. Discovery and evaluation of novel antiinflammatory derivatives of natural bioactive curcumin. Drug Des Devel Ther. 8:2161-2171.



  • There are currently no refbacks.

Copyright (c) 2020 Indonesian Journal of Pharmacy

Creative Commons License
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.

Indonesian J Pharm indexed by:

analytics View My Stats