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Current Drug Discovery Technologies

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ISSN (Print): 1570-1638
ISSN (Online): 1875-6220

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Research Article

Docking Studies of Curcumin and Analogues with Various Phosphodiesterase 4 Subtypes

Author(s): Yau Xin Yi, Anand Gaurav* and Gabriel A. Akowuah

Volume 17, Issue 2, 2020

Page: [248 - 260] Pages: 13

DOI: 10.2174/1570163815666181017091655

Price: $65

Abstract

Introduction: The primary aim of this study is to understand the binding of curcumin and its analogues to different PDE4 subtypes and identify the role of PDE4 subtype inhibition in the anti-inflammatory property of curcumin. Docking analysis has been used to acquire the above mentioned structural information and this has been further used for designing of curcumin derivatives with better anti-inflammatory activity.

Materials and Methods: Curcumin and its analogues were subjected to docking using PDE4A, PDE4B, PDE4C and PDE4D as the targets. A data set comprising 18 analogues of curcumin, was used as ligands for docking of PDE4 subtypes. Curcumin was used as the standard for comparison. Docking was performed using AutoDock Vina 1.1.2 software integrated in LigandScout 4.1. During this process water molecules were removed from proteins, charges were added and receptor structures were minimised by applying suitable force fields. The docking scores were compared, and the selectivity of compounds for PDE4B over PDE4D was calculated as well.

Results: All curcumin analogues used in the study showed good binding affinity with all PDE4 subtypes, with evident selectivity towards PDE4B subtype. Analogue A11 provides the highest binding affinity among all ligands.

Conclusion: Curcumin and analogues have moderate to strong affinity towards all PDE4 subtypes and have evident selectivity towards PDE4B. The Oxygen atom of the methoxy group plays a key role in PDE4B binding and any alterations could interfere with the binding. Tetrahydropyran side chain and heterocyclic rings are also suggested to be helpful in PDE4B binding.

Keywords: PDE4B selectivity, docking study, curcumin and analogues, PDE4 subtype inhibition, anti-inflammatory property, binding affinity

Graphical Abstract

[1]
Sharma RA, Steward WP, Gescher AJ. Pharmacokinetics and pharmacodynamics of curcumin. Adv Exp Med Biol 2007; 595: 453-70.
[http://dx.doi.org/10.1007/978-0-387-46401-5_20] [PMID: 17569224]
[2]
Narayanaswamy R, Wai LK, Abas F, Ismail IS. Molecular docking analysis of curcumin analogues as human neutrophil elastase inhibitors. Bangladesh J Pharmacol 2014; 9(1): 77-82.
[http://dx.doi.org/10.3329/bjp.v9i1.17474]
[3]
Savcun GY, Ozkan E, Dulundu E, et al. Antioxidant and Anti-inflammatory Effects of Curcumin Against Hepatorenal Oxidative Injury in the Experimental Sepsis Model Created in Rats. Turkish J Trauma Emerg Surg [Internet] 2013; 19(6): 507-15.
[http://dx.doi.org/10.5505/tjtes.2013.76390]
[4]
Leitman IM. Curcumin for the prevention of acute lung injury in sepsis: is it more than the flavor of the month? J Surg Res 2012; 176(1): e5-7.
[http://dx.doi.org/10.1016/j.jss.2011.11.1034] [PMID: 22316673]
[5]
Eskandari N, Mirmosayyeb O, Andalib A. A short review on structure and role of cyclic-3’,5’-adenosine monophosphate-specific phosphodiesterase 4 as a treatment tool. J Res Pharm Pr [Internet] ; 4(4): 175-81.
[6]
Lugnier C. Cyclic nucleotide phosphodiesterase (PDE) superfamily: a new target for the development of specific therapeutic agents. Pharmacol Ther 2006; 109(3): 366-98.
[http://dx.doi.org/10.1016/j.pharmthera.2005.07.003] [PMID: 16102838]
[7]
Wang H, Peng M-S, Chen Y, et al. Structures of the four subfamilies of phosphodiesterase-4 provide insight into the selectivity of their inhibitors. Biochem J 2007; 408(2): 193-201. [Internet].
[http://dx.doi.org/10.1042/BJ20070970] [PMID: 17727341]
[8]
Manning CD, Burman M, Christensen SB, et al. Suppression of human inflammatory cell function by subtype-selective PDE4 inhibitors correlates with inhibition of PDE4A and PDE4B. Br J Pharmacol 1999; 128(7): 1393-8.
[http://dx.doi.org/10.1038/sj.bjp.0702911] [PMID: 10602317]
[9]
Jørgensen C, Yasmeen S, Iversen HK, Kruuse C. Phosphodiesterase4D (PDE4D)--A risk factor for atrial fibrillation and stroke? J Neurol Sci 2015; 359(1-2): 266-74.
[http://dx.doi.org/10.1016/j.jns.2015.11.010] [PMID: 26671126]
[10]
Berman HM, Westbrook J, Feng Z, et al. The protein data bank. Nucleic Acids Res 2000; 28(1): 235-42.
[http://dx.doi.org/10.1093/nar/28.1.235] [PMID: 10592235]
[11]
Corporation C. PerkinElmer Informatics Desktop Software [Internet]. Cambridgesoftcom; 2015.Available from: . http://www.cambridgesoft.com/software/chemdraw/
[12]
Liang G, Li X, Chen L, et al. Synthesis and anti-inflammatory activities of mono-carbonyl analogues of curcumin. Bioorg Med Chem Lett 2008; 18(4): 1525-9.
[http://dx.doi.org/10.1016/j.bmcl.2007.12.068] [PMID: 18234497]
[13]
Wang ZS, Chen LZ, Zhou HP, Liu XH, Chen FH. Diarylpentadienone derivatives (curcumin analogues): Synthesis and anti-inflammatory activity. Bioorg Med Chem Lett 2017; 27(8): 1803-7.
[http://dx.doi.org/10.1016/j.bmcl.2017.02.056] [PMID: 28284806]
[14]
Zhang Y, Liang D, Dong L, et al. Anti-inflammatory effects of novel curcumin analogs in experimental acute lung injury. Respir Res 2015; 16(43): 43.
[http://dx.doi.org/10.1186/s12931-015-0199-1] [PMID: 25889862]
[15]
Dassault Systemes BIOVIA. Discovery Studio Modeling Environment. San Diego: Dassault Systemes 2016.
[16]
Wolber G, Langer T. LigandScout: 3-D pharmacophores derived from protein-bound ligands and their use as virtual screening filters. J Chem Inf Model 2005; 45(1): 160-9.
[http://dx.doi.org/10.1021/ci049885e] [PMID: 15667141]
[17]
Vyas A, Dandawate P, Padhye S, Ahmad A, Sarkar F. Perspectives on new synthetic curcumin analogs and their potential anticancer properties. Curr Pharm Des 2013; 19(11): 2047-69.
[PMID: 23116312]
[18]
Zhang C, Xu Y, Zhang H-T, Gurney ME, O’Donnell JM. Comparison of the Pharmacological Profiles of Selective PDE4B and PDE4D Inhibitors in the Central Nervous System. Sci Rep 2017; 7(January): -. 40115. [Internet].
[http://dx.doi.org/10.1038/srep40115] [PMID: 28054669]
[19]
Liang G, Yang S, Zhou H, et al. Synthesis, crystal structure and anti-inflammatory properties of curcumin analogues. Eur J Med Chem 2009; 44(2): 915-. [Internet].
[http://dx.doi.org/10.1016/j.ejmech.2008.01.031] [PMID: 18336957]
[20]
Fukunishi Y, Nakamura H. Integration of ligand-based drug screening with structure-based drug screening by combining maximum volume overlapping score with ligand docking. Pharmaceuticals (Basel) 2012; 5(12): 1332-45.
[http://dx.doi.org/10.3390/ph5121332] [PMID: 24281339]
[21]
Fox D III, Burgin AB, Gurney ME. Structural basis for the design of selective phosphodiesterase 4B inhibitors. Cell Signal 2014; 26(3): 657-63.
[http://dx.doi.org/10.1016/j.cellsig.2013.12.003] [PMID: 24361374]

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