Novel heterocyclic hybrid of 2-(aryl)-1H-indene-1,3(2H)-dione targeting tyrosinase: design, biological evaluation and in silico studies

Document Type: Original Article

Authors

1 Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, 71348 Shiraz, Iran Central Research Laboratory, Shiraz University of Medical Sciences, 71468 Shiraz, Iran

2 b Department of Medicinal Chemistry, Faculty of Pharmacy, Shiraz University of Medical Sciences, 71345 Shiraz, Iran

3 Department of Medicinal Chemistry, Faculty of Pharmacy, Shiraz University of Medical Sciences, 71345 Shiraz, Iran

4 Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, 71348 Shiraz, Iran

5 a Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, 71348 Shiraz, Iran

6 Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, 71348 Shiraz, Iran Department of Medicinal Chemistry, Faculty of Pharmacy, Shiraz University of Medical Sciences, 71345 Shiraz, Iran

10.30476/tips.2020.88203.1068

Abstract

Melanogenesis is a process of melanin synthesize, which is a primary response for the pigmentation of human skin. Tyrosinase is a key enzyme, which catalyzes a rate-limiting step of the melanin formation, natural products have shown potent inhibitors, but some of these possess toxicity. Numerous synthetic inhibitors have been developed in recent years may lead to the potent anti-tyrosinase agents. Therefore its inhibition may be an efficient way for the development of depigmenting agents. A novel series of 2-arylidine-1H-indene-1,3(2H)-dione analogs were designed, synthesized and screened for their in vitro tyrosinase inhibitory activity. 3d derivative bearing nitrothiophene revealed excellent anti-tyrosinase activity with an IC50 value of 3.55 μM comparable to kojic acid as a positive control. 3d as the most potent inhibitor and 3f as the least active derivative were subjected to in silico evaluations considering the 3D conformations, ΔGb of bindings and interactions within the active site of tyrosinase. 

Keywords


1. Zolghadri S, Bahrami A, Hassan Khan MT, et al. A comprehensive review on tyrosinase inhibitors. J Enzyme Inhib Med Chem. 2019;34(1):279-309. doi:10.1080/14756366.2018.1545767
2. Drescher DG, Selvakumar D, Drescher MJ. Analysis of Protein Interactions by Surface Plasmon Resonance. Adv Protein Chem Struct Biol. 2018;110:1-30. doi: 10.1016/bs.apcsb.2017.07.003. Epub 2017 Sep 12. PMID: 29412994.
3. Jus S, Guebitz GM, Kokol V. Enzyme-Catalysed Coupling of Functional Antioxidants onto Protein Fibres. In: Anand SC, Kennedy JF, Miraftab M, Rajendran S, editors. Medical and Healthcare Textiles: Woodhead Publishing; 2010. p. 126-34.
4. Jungbluth AA, Busam KJ. 29 - Immunohistochemistry for the Diagnosis of Melanocytic Proliferations. In: Busam KJ, Gerami P, Scolyer RA, editors. Pathology of Melanocytic Tumors. Philadelphia: Elsevier; 2019. p. 348-63.
5. Hosseinpoor H, Iraji A, Edraki N, Pirhadi S, Attarroshan M, Khoshneviszadeh M, Khoshneviszadeh M. A Series of Benzylidenes Linked to Hydrazine-1-carbothioamide as Tyrosinase Inhibitors: Synthesis, Biological Evaluation and Structure-Activity Relationship. Chem Biodivers. 2020 Aug;17(8):e2000285. doi: 10.1002/cbdv.202000285. Epub 2020 Aug 3. PMID: 32478439.
6. Iraji A, Khoshneviszadeh M, Bakhshizadeh P, Edraki N, Khoshneviszadeh M. Structure-Based Design, Synthesis, Biological Evaluation and Molecular Docking Study of 4-Hydroxy-N'-methylenebenzohydrazide Derivatives Acting as Tyrosinase Inhibitors with Potentiate Anti-Melanogenesis Activities. Med Chem. 2020;16(7):892-902. doi: 10.2174/1573406415666190724142951. PMID: 31339074.
7. Messerschmidt A. 8.14 - Copper Metalloenzymes. In: Liu H-W, Mander L, editors. Comprehensive Natural Products II. Oxford: Elsevier; 2010. p. 489-545.
8. Karimian S, Ranjbar S, Dadfar M, Khoshneviszadeh M, Gholampour M, Sakhteman A, Khoshneviszadeh M. 4H-benzochromene derivatives as novel tyrosinase inhibitors and radical scavengers: synthesis, biological evaluation, and molecular docking analysis. Mol Divers. 2020 Jul 18. doi: 10.1007/s11030-020-10123-0. Epub ahead of print. PMID: 32683615.
9. Lolak N, Boga M, Tuneg M, Karakoc G, Akocak S, Supuran CT. Sulphonamides incorporating 1,3,5-triazine structural motifs show antioxidant, acetylcholinesterase, butyrylcholinesterase, and tyrosinase inhibitory profile. J Enzyme Inhib Med Chem. 2020 Dec;35(1):424-431. doi: 10.1080/14756366.2019.1707196. PMID: 31899985; PMCID: PMC6968691.
10. Ranjbar S, Shahvaran PS, Edraki N, Khoshneviszadeh M, Darroudi M, Sarrafi Y, Hamzehloueian M, Khoshneviszadeh M. 1,2,3-Triazole-linked 5-benzylidene (thio)barbiturates as novel tyrosinase inhibitors and free-radical scavengers. Arch Pharm (Weinheim). 2020 Oct;353(10):e2000058. doi: 10.1002/ardp.202000058. Epub 2020 Jul 8. PMID: 32638438.
11. Hałdys K, Goldeman W, Jewgiński M, Wolińska E, Anger-Góra N, Rossowska J, Latajka R. Halogenated aromatic thiosemicarbazones as potent inhibitors of tyrosinase and melanogenesis. Bioorg Chem. 2020 Jan;94:103419. doi: 10.1016/j.bioorg.2019.103419. Epub 2019 Nov 9. PMID: 31761412.
12. Iraji A, Adelpour T, Edraki N, Khoshneviszadeh M, Miri R, Khoshneviszadeh M. Synthesis, biological evaluation and molecular docking analysis of vaniline-benzylidenehydrazine hybrids as potent tyrosinase inhibitors. BMC Chem. 2020 Apr 7;14(1):28. doi: 10.1186/s13065-020-00679-1. PMID: 32280949; PMCID: PMC7137441.
13. Patravale AA, Gore AH, Kolekar GB, Deshmukh MB, Choudhari PB, Bhatia MS, et al. Synthesis, biological evaluation and molecular docking studies of some novel indenospiro derivatives as anticancer agents. J Taiwan Inst Chem Eng. 2016;68:105-18.
14. Beck DE, Lv W, Abdelmalak M, Plescia CB, Agama K, Marchand C, Pommier Y, Cushman M. Synthesis and biological evaluation of new fluorinated and chlorinated indenoisoquinoline topoisomerase I poisons. Bioorg Med Chem. 2016 Apr 1;24(7):1469-79. doi: 10.1016/j.bmc.2016.02.015. Epub 2016 Feb 9. PMID: 26906474; PMCID: PMC4789169.
15. Fadda A, Khalil A, Tawfik E. Enaminonitriles in heterocyclic synthesis: Synthesis and biological evaluation of novel indeno[2,1-b]thiophene derivatives.Turk J Chem. 2013;37:134-48.
16. Khalifa NM, Al-Omar MA, Amr AE-GE, Baiuomy AR, Abdel-Rahman RF. Synthesis and biological evaluation of some novel fused thiazolo[3,2-a]pyrimidines as potential analgesic and anti-inflammatory agents. Bioorg Khim. 2015 Mar-Apr;41(2):218-26. doi: 10.7868/s0132342315020098. PMID: 26165129.
17. Catto M, Aliano R, Carotti A, Cellamare S, Palluotto F, Purgatorio R, De Stradis A, Campagna F. Design, synthesis and biological evaluation of indane-2-arylhydrazinylmethylene-1,3-diones and indol-2-aryldiazenylmethylene-3-ones as beta-amyloid aggregation inhibitors. Eur J Med Chem. 2010 Apr;45(4):1359-66. doi: 10.1016/j.ejmech.2009.12.029. Epub 2009 Dec 23. PMID: 20137834.
18. Khan G, Aftab MF, Bano B, Khan KM, Murtaza M, Siddiqui S, Rehman MH, Waraich RS. A new indanedione derivative alleviates symptoms of diabetes by modulating RAGE-NF-kappaB pathway in db/db mice. Biochem Biophys Res Commun. 2018 Jul 2;501(4):863-870. doi: 10.1016/j.bbrc.2018.05.043. Epub 2018 May 21. PMID: 29778537.
19. Iraji A, Firuzi O, Khoshneviszadeh M, Nadri H, Edraki N, Miri R. Synthesis and structure-activity relationship study of multi-target triazine derivatives as innovative candidates for treatment of Alzheimer's disease. Bioorg Chem. 2018 Apr;77:223-235. doi: 10.1016/j.bioorg.2018.01.017. Epub 2018 Jan 16. PMID: 29367079.
20. Yazdani M, Edraki N, Badri R, Khoshneviszadeh M, Iraji A, Firuzi O. Multi-target inhibitors against Alzheimer disease derived from 3-hydrazinyl 1,2,4-triazine scaffold containing pendant phenoxy methyl-1,2,3-triazole: Design, synthesis and biological evaluation. Bioorg Chem. 2019 Mar;84:363-371. doi: 10.1016/j.bioorg.2018.11.038. Epub 2018 Nov 29. PMID: 30530107.
21. Iraji A, Nouri A, Edraki N, Pirhadi S, Khoshneviszadeh M, Khoshneviszadeh M. One-pot synthesis of thioxo-tetrahydropyrimidine derivatives as potent β-glucuronidase inhibitor, biological evaluation, molecular docking and molecular dynamics studies. Bioorg Med Chem. 2020 Apr 1;28(7):115359. doi: 10.1016/j.bmc.2020.115359. Epub 2020 Feb 6. PMID: 32098709.
22. Kim YJ. Rhamnetin attenuates melanogenesis by suppressing oxidative stress and pro-inflammatory mediators. Biol Pharm Bull. 2013;36(8):1341-7. doi: 10.1248/bpb.b13-00276. Epub 2013 Jun 4. PMID: 23739488.
23. Ismaya WT, Rozeboom HJ, Weijn A, Mes JJ, Fusetti F, Wichers HJ, Dijkstra BW. Crystal structure of Agaricus bisporus mushroom tyrosinase: identity of the tetramer subunits and interaction with tropolone. Biochemistry. 2011 Jun 21;50(24):5477-86. doi: 10.1021/bi200395t. Epub 2011 May 27. PMID: 21598903.
24. Lee TH, Seo JO, Baek SH, Kim SY. Inhibitory effects of resveratrol on melanin synthesis in ultraviolet B-induced pigmentation in Guinea pig skin. Biomol Ther (Seoul). 2014;22(1):35-40. doi:10.4062/biomolther.2013.081
25. Pillaiyar T, Namasivayam V, Manickam M, Jung SH. Inhibitors of Melanogenesis: An Updated Review. J Med Chem. 2018 Sep 13;61(17):7395-7418. doi: 10.1021/acs.jmedchem.7b00967. Epub 2018 May 24. PMID: 29763564.
26. Lee SY, Baek N, Nam TG. Natural, semisynthetic and synthetic tyrosinase inhibitors. J Enzyme Inhib Med Chem. 2016;31(1):1-13. doi: 10.3109/14756366.2015.1004058. Epub 2015 Feb 16. PMID: 25683082.
27. Tan X, Song YH, Park C, Lee KW, Kim JY, Kim DW, Kim KD, Lee KW, Curtis-Long MJ, Park KH. Highly potent tyrosinase inhibitor, neorauflavane from Campylotropis hirtella and inhibitory mechanism with molecular docking. Bioorg Med Chem. 2016 Jan 15;24(2):153-9. doi: 10.1016/j.bmc.2015.11.040.
28. Hu X, Wang M, Yan GR, Yu MH, Wang HY, Hou AJ. 2-Arylbenzofuran and tyrosinase inhibitory constituents of Morus notabilis. J Asian Nat Prod Res. 2012;14(12):1103-8. doi: 10.1080/10286020.2012.724400.
29. Zhu JJ, Yan GR, Xu ZJ, Hu X, Wang GH, Wang T, Zhu WL, Hou AJ, Wang HY. Inhibitory Effects of (2'R)-2',3'-dihydro-2'-(1-hydroxy-1-methylethyl)-2,6'-bibenzofuran-6,4'-diol on Mushroom Tyrosinase and Melanogenesis in B16-F10 Melanoma Cells. Phytother Res. 2015 Jul;29(7):1040-5. doi: 10.1002/ptr.5344.
30. Okombi S, Rival D, Bonnet S, Mariotte AM, Perrier E, Boumendjel A. Discovery of benzylidenebenzofuran-3(2H)-one (aurones) as inhibitors of tyrosinase derived from human melanocytes. J Med Chem. 2006 Jan 12;49(1):329-33. doi: 10.1021/jm050715i.
31. Jung HJ, Noh SG, Park Y, et al. In vitro and in silico insights into tyrosinase inhibitors with (E)-benzylidene-1-indanone derivatives. Comput Struct Biotechnol J. 2019;17:1255-1264. Published 2019 Aug 1. doi:10.1016/j.csbj.2019.07.017
32. Messerschmidt A. Copper Metalloenzymes. Comprehensive Natural Products II: Chem.Bio. 2010;8:489-545.