Bambang Wijianto, Ritmaleni, Hari Purnomo, Arief Nurrochmad
Bambang Wijianto1,3, Ritmaleni1*, Hari Purnomo1, Arief Nurrochmad2
1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia.
2Department of Pharmacology, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia.
3Department of Pharmaceutical Chemistry, Faculty of Medicine, Universitas Tanjungpura, Pontianak, Indonesia.
Volume - 13,
Issue - 10,
Year - 2020
The objective of this study was to design new mono-ketone analogs of curcumin and determine its lipid peroxidation inhibition. Molecular modeling studies were carried out by using the semi-empirical quantum chemical algorithm AM-1 method in MOE 2018.01.01 software. Build QSAR was used to generate an equation model that will be used to design new mono-ketone analogs of curcumin. Synthesis of new compounds produced from an aldol condensation reaction. Thiobarbituric acid reactive substance (TBARS) method was used to determine antioxidant activity by measuring lipid peroxide concentration. Promising predictions values of lipid peroxidation the QSAR study obtained inhibitory activity. The in vitro lipid peroxidation inhibition of 2,6-bis-(3'-ethoxy, 4'-hydroxybenzylidene)-cyclohexanone; 2,6-bis-(3'-Bromo,4'-methoxybenzylidene)-cyclohexanone; and 2,6-bis-(3',4'-dimethoxybenzylidene)-cyclohexanone indicates good inhibitory with IC50 values of 2.95; 0.95; and 2.45µM respectively. The new mono-ketone analogs of curcumin compound from the QSAR study has been shown to have antioxidant activity by inhibiting lipid peroxidation by scavenging free radicals.
Cite this article:
Bambang Wijianto, Ritmaleni, Hari Purnomo, Arief Nurrochmad. Quantitative Structure Activity Relationship (QSAR) study and Biological evaluation on Mono-ketone analogs of Curcumin as Antioxidant. Research J. Pharm. and Tech. 2020; 13(10):4829-4835. doi: 10.5958/0974-360X.2020.00850.1
1. Heim KE, Tagliaferro AR, Bobilya DJ. Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships. J Nutri Biochem 2002; 13: 572-584.
2. Witschi HP. Enhanced tumour development by butylated hydroxytoluene (BHT) in the liver, lung and gastro-intestinal tract. Fd Chem. Toxic 1986; 24: 1127-113.
3. Gülçin I, Mshvildadze V, Gepdiremen A and Elias R. The antioxidant activity of a triterpenoid glycoside isolated from the Berries of Hedera colchica: 3-o-(β-D-glucopyranosyl)-hederagenin. Phytother. Res. 2006; 20: 130–134.
4. Oktay M, Gulcin I, Kufrevioglub OI. Determination of in vitro antioxidant activity of fennel (Foeniculum vulgare) seed extracts. Lebensm.-Wiss. U.-Technol 2003; 36: 263–271
5. Tuba AK, Gulcin I. Antioxidant and radical scavenging properties of curcumin. Chemico-Biological Interactions 2008; 174: 27–37.
6. Reddy ACP, Lokesh BR. Studies on the inhibitory effects of curcumin and eugenol on the formation of reactive oxygen species and the oxidation of ferrous iron. Molecular and Cellular Biochemistry 1994; 137: 1-8.
7. Sreejayan, Rao NA. Curcuminoids as potent inhibitors of lipid peroxidation. J. Pharm. Pharmacol 1994; 46: 1013-1016.
8. Jovanovic SV, Boone CW, Steenken, Trinoga M, Kaskey RB. How curcumin works preferentially with water soluble antioxidants. J. Am. Chem. Soc 2001; 123: 3064-3068.
9. Selvam C, Jachak SM, Thilagavathib R, Chakraborti AK. Design, synthesis, biological evaluation and molecular docking of curcumin analogues as antioxidant, cyclooxygenase inhibitory and anti-inflammatory agents. Bioorganic and Medicinal Chemistry Letters 2005; 15: 1793–1797.
10. Wijianto B, Ritmaleni, Purnomo H, Nurrochmad A. In silico and in vitro assay of HGV analogue as antibacterial. Int J Pharm Pharm Sci 2019; 11: 78-85.
11. Medina-Franco JL, Yoo J. Molecular modeling and virtual screening of DNA methyltransferase inhibitors. Curr Pham Des 2013; 19: 2138-47.
12. Ujihara M, Tsuchida S, Satoh K, Sato H, Urade Y. Biochemical and immunological demonstration of prostaglandin H2 by various GSTs isoenzymes. Archs. Biochem. Biophys 1988; 264: 428-437.
13. Ramírez Durán LA, Rosales-Hernández MC, Hernández-Rodríguez M, Mendieta-Wejebe JE, Ferrara JT and Correa-Basurto J. Mapping myeloperoxidase to identify its promiscuity properties using docking and molecular dynamics simulations. Curr Pham Des 2013; 19: 2204-15.
14. Sardjiman, Reksohadiprodjo MS, Hakim L, Van der Goot H, 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.
15. De Oliveira DB, Gaudio AC. BuildQSAR: A New Computer Program for QSAR Analysis. Quant. Struct.-act. Relat 2000; 19: 599-601.
16. Istyastono EP, Martono S, Prawono HD, Tahir I. Quantitative Structure-Activity Relationship analysis of curcumin and its derivatives as GST inhibitors based on computational chemistry calculation. Indonesian Journal of Chemistry 2003; 3; 179-18.
17. Ruiz-Larrea B, Leal AM, Liza M, Lacort M, de Groot H. Antioxidant effects of estradiol and 2-hydroxyestradiol on iron-induced lipid peroxidation of rat liver microsomes. Steroids 1994; 59: 383-388.
18. Moore K, Roberts LJ. Measurement of lipid peroxidation. Free Radical Research 1998; 28: 659–671.
19. Yuniarti N, Nugroho PA, Asyhar A, Sardjiman, Ikawati Z, Istyastono EP. In vitro and In Silico studies on curcumin and its analogues as dual inhibitors for cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). ITB J. Sci. 2012; 44 A: 51-66.
20. Yagi K. Simple assay for the level of total lipid peroxides in serum or plasma. Methods Mol Biol 1998; 108:101-106.
21. Conti M, Morand P, Levillain P, Lemonnier A. 1991. Improved fluorometric determination of malonaldehyde. Clinical chemistry 1991; 37: 1273–5.
22. 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.
23. Hayun, Maggadani BP, Kurnia A, Hanifah A, Yuliandi M, Fitriyani I, Hadrianti SP. 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. Int J App Pharm 2019; 11: 246-250.
24. Setyawan EI, Setyowati EP, Rohman A, Nugroho AK. Central composite design for optimizing extraction of EGCG from green tea leaf (Camellia sinensis l.). Int J App Pharm 2018; 10: 211-216.