ANTI-INFLAMMATORY AND ANTIOXIDANT ACTIVITY OF SYNTHESIZED MANNICH BASE DERIVATIVES OF (2E,6E)-2-[(4-HYDROXY-3-METHOXYPHENYL)METHYLIDENE]-6-(PHENYL METHYLIDENE)CYCLOHEXAN-1-ONE

HAYUN HAYUN; BAITHA PALANGGATAN MAGGADANI; ARINI KURNIA; AULIA HANIFAH; MEIDI YULIANDI; IDA FITRIYANI; SEPTIANI PUTRI HADRIANTI

doi:10.22159/ijap.2019.v11s1.19448

Authors

HAYUN HAYUN Laboratory of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmacy, Universitas Indonesia, Depok 16424, West Java, Indonesia.
BAITHA PALANGGATAN MAGGADANI Laboratory of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmacy, Universitas Indonesia, Depok 16424, West Java, Indonesia.
ARINI KURNIA Laboratory of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmacy, Universitas Indonesia, Depok 16424, West Java, Indonesia.
AULIA HANIFAH Laboratory of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmacy, Universitas Indonesia, Depok 16424, West Java, Indonesia.
MEIDI YULIANDI Laboratory of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmacy, Universitas Indonesia, Depok 16424, West Java, Indonesia.
IDA FITRIYANI Laboratory of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmacy, Universitas Indonesia, Depok 16424, West Java, Indonesia.
SEPTIANI PUTRI HADRIANTI Laboratory of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmacy, Universitas Indonesia, Depok 16424, West Java, Indonesia.

DOI:

https://doi.org/10.22159/ijap.2019.v11s1.19448

Keywords:

Asymmetrical mono-carbonyl analogs of curcumin, Mannich bases, Antiinflammatory, Antioxidant

Abstract

Objective: To further understand this compound, we synthesized and evaluated the antioxidant and anti-inflammatory activity of a series of its
Mannich base derivatives.
Methods: We synthesized the compounds via the previously reported Mannich reaction method. Their structures were elucidated by Fouriertransform
infrared,1H-NMR,13C-NMR, and high-resolution mass spectra. The derivatives’ anti-inflammatory and antioxidant activities were tested
using the inhibition of protein denaturation method and the 2,2-diphenyl-2-picrylhydrazyl free radical scavenging assay.
Results: The IC50 values for the anti-inflammatory activity of the 2,6-dimethylmorpholine, pyrrolidine, 1-methylpiperazine, and dimethylamine
Mannich base derivatives 2a–d were 10.67, 10.72, 37.75, and 1.93 μM, respectively; for (2E,6E)-2-({4-hydroxy-3-methoxyphenyl}methylidene)-6-
(phenylmethylidene)cyclohexan-1-one (1), diclofenac sodium, and curcumin, the IC50 values were 56.29, 1.52, and 8.43 μM, respectively. The IC50
values for the antioxidant activity of compounds 2a–2d were 229.62, 57.29, 280.43, and 219.22 μM, respectively; for compound 1, quercetin, and
curcumin, the IC50 values were 144.22, 27.28, and 26.45 μM, respectively.
Conclusion: Substituting Mannich bases into (2E,6E)-2-[(4-hydroxy-3-methoxyphenyl) methylidene]-6-(phenylmethylidene)cyclohexan-1-one
enhanced its anti-inflammatory activity, but lowered its antioxidant activity. Compound 2d, (2E,6E)-2-({3-[(dimethylamino)methyl]-4-hydroxy-5-
methoxyphenyl}methylidene)-6-(phenyl methylidene)cyclohexan-1-one, exhibited potent anti-inflammatory activity comparable to diclofenac
sodium and four times higher than curcumin. However, further investigation of this compound’s mechanism of action and toxicity is warranted.

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References

1. Lal J, Gupta SK, Thavaselvam D, Agarwal DD. Synthesis and
pharmacological activity evaluation of curcumin derivatives. Chin
Chem Let 2016;27:1067-72.
2. Anand P, Thomas SG, Kunnumakkara AB, Sundaram C, Harikumar KB,
Sung B, et al. Biological activities of curcumin and its analogues
(Congeners) made by man and mother nature. Biochem Pharmacol
2008;76:1590-611.
3. Zhang Y, Zhao L, Wu J, Jiang X, Dong L, Xu F, et al. Synthesis and
evaluation of a series of novel asymmetrical curcumin analogs for the
treatment of inflammation. Molecules 2014;19:7287-307.
4. Zhao C, Liu Z, Liang G. Promising curcumin-based drug design:
Mono-carbonyl analogues of curcumin (MACs). Curr Pharm Des
2013;19:2114-35.
5. Lamperti M, Maspero A, Tønnesen HH, Bondani M, Nardo L.
Elucidation of the relationships between H-bonding patterns and
excited state dynamics in cyclovalone. Molecules 2014;19:13282-304.
6. Zhang Y, Jiang X, Peng K, Chen C, Fu L, Wang Z, et al. Discovery and
evaluation of novel anti-inflammatory derivatives of natural bioactive
curcumin. Drug Des Devel Ther 2014;8:2161-71.
7. Mohd Aluwi MFF, Rullah K, Yamin BM, Leong SW, Abdul Bahari MN,
Lim SJ, et al. 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 Lett 2016;26:2531-8.
8. Li Q, Chen J, Luo S, Xu J, Huang Q, Liu T, et al. Synthesis and
assessment of the antioxidant and antitumor properties of asymmetric
curcumin analogues. Eur J Med Chem 2015;93:461-9.
9. Putri TN, Bachtiar A, Hayun H. 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 2018;8:19-25.
10. Bala S, Sharma N, Kajal A, Kamboj S, Saini V. Mannich bases: An
important pharmacophore in present scenario. Int J Med Chem
2014;2014:1-15.
11. Prasetyaningrum PW, Bahtiar A, Hayun H. Synthesis and
antiproliferative activity of diethylamine mannich base of asymmetrical
mono-carbonyl curcumin analogs against HeLa cell lines. Sci Pharm
2018;86:25.
12. Untung J, Iskandarsyah I. Hayun, H. 2-[(2,6-Dimethylmorpholin-4-yl)
methyl]-4-[(E)-2-{3-[(E)-2-{3-[(2,6-dimethylmorpholin-4-yl)methyl]-
4-hydroxy-5-methoxyphenyl}ethenyl]-1H-pyrazol-5-yl}ethenyl]-6-
methoxyphenol. Molbank 2017;3:M949.
13. Hayun H, Jatmika C, Maswati EM, Salim S, Fajriawan AA,
Nareswara AD, et al. Synthesis and free radical scavenging activities
of di-mannich bases of cyclovalone derivatives. Orient J Chem
2017;33:2742-57.
14. Aksoy L, Kolay E, A??lönü Y, Aslan Z, Karg?o?lu M. Free radical
scavenging activity, total phenolic content, total antioxidant status, and
total oxidant status of endemic Thermopsis turcica. Saudi J Biol Sci
2013;20:235-9.
15. Silverstein RM, Webster FX, Kiemle DJ. Spectrometric Identification
of Organic Compounds. 7th ed. New York, USA: John Wiley and Sons,
Inc.; 2014.
16. Umapathy E, Ndebia EJ, Meeme A, Adam B, Menziwa P,
Nkeh-Chungag BN, et al. 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
2010;4:789-95.
17. Jagtap VA, Agasimundim YS, Jayachandran E, Sathe BS.
In vitro anti-inflammatory activity of 2-amino-3-(substituted
benzylidinecarbohydrazide)-4,5,6,7- tetrahydrobenzothiophenes.
J Pharm Res 2011;4:378-9.
18. Chandra S., Chatterjee P, Dey P, Bhattacharya S. Evaluation of in vitro
anti-inflammatory activity of coffee against the denaturation of protein.
Asian Pac J Trop Biomed 2012;2:S178-80.
19. Sujith KV, Rao JN, Shetty P, Kalluraya B. Regioselective reaction:
Synthesis and pharmacological study of mannich bases containing
ibuprofen moiety. Eur J Med Chem 2009;44:3697-702.
20. Dontha S. A review on antioxidant methods. Asian J Pharm Clin Res
2016;9:14-32.
21. Hayun H, Arrahman A, Purwati EM, Yanuar A, Fortunata F, Suhargo F,
et al. Synthesis, anti-inflammatory, and antioxidant activity of mannich
bases of dehydrozingerone derivatives. J Young Pharm 2018;10:s6-10.
22. Zheng QT, Yang ZH, Yu LY, Ren YY, Huang QX, Liu Q, et al. Synthesis
and antioxidant activity of curcumin analogs. J Asian Nat Prod Res
2017;19:489-503.
23. Itokawa H, Shi Q, Akiyama T, Morris-Natschke SL, Lee KH. Recent
advances in the investigation of curcuminoids. Chin Med 2008;3:11.