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Anti-Cancer Agents in Medicinal Chemistry

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ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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Research Article

Evaluation of Cytotoxic and Tyrosinase Inhibitory Activities of 2-phenoxy(thiomethyl) pyridotriazolopyrimidines: In Vitro and Molecular Docking Studies

Author(s): Hatem A. Abuelizz, El Hassane Anouar, Mohamed Marzouk, Mizaton H. Hasan, Siti R. Saleh, Adi Ahudhaif, Khalid A. Alburikan and Rashad Al-Salahi*

Volume 20, Issue 14, 2020

Page: [1714 - 1721] Pages: 8

DOI: 10.2174/1871520620666200627212128

Price: $65

Abstract

Background: The use of tyrosinase has confirmed to be the best means of recognizing safe, effective, and potent tyrosinase inhibitors for whitening skin. Twenty-four 2-phenoxy(thiomethyl)pyridotriazolopyrimidines were synthesized and characterized in our previous studies.

Objective: The present work aimed to evaluate their cytotoxicity against HepG2 (hepatocellular carcinoma), A549 (pulmonary adenocarcinoma), MCF-7 (breast adenocarcinoma) and WRL 68 (embryonic liver) cell lines.

Methods: MTT assay was employed to investigate the cytotoxicity, and a tyrosinase inhibitor screening kit was used to evaluate the Tyrosinase (TYR) inhibitory activity of the targets.

Results: The tested compounds exhibited no considerable cytotoxicity, and nine of them were selected for a tyrosinase inhibitory test. Compounds 2b, 2m, and 5a showed good inhibitory percentages against TYR compared to that of kojic acid (reference substance). Molecular docking was performed to rationalize the Structure-Activity Relationship (SAR) of the target pyridotriazolopyrimidines and analyze the binding between the docked-selected compounds and the amino acid residues in the active site of tyrosinase.

Conclusion: The target pyridotriazolopyrimidines were identified as a new class of tyrosinase inhibitors.

Keywords: Pyridotriazolopyrimidine, tyrosinase inhibition, cytotoxicity, molecular docking, HepG2, MCF-7.

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[1]
Ielo, L.; Deri, B.; Germanò, M.P.; Vittorio, S.; Mirabile, S.; Gitto, R.; Rapisarda, A.; Ronsisvalle, S.; Floris, S.; Pazy, Y.; Fais, A.; Fishman, A.; De Luca, L. Exploiting the 1-(4-fluorobenzyl)piperazine fragment for the development of novel tyrosinase inhibitors as anti-melanogenic agents: Design, synthesis, structural insights and biological profile. Eur. J. Med. Chem., 2019, 178, 380-389.
[http://dx.doi.org/10.1016/j.ejmech.2019.06.019] [PMID: 31202126]
[2]
Bang, E.; Noh, S.G.; Ha, S.; Jung, H.J.; Kim, D.H.; Lee, A.K.; Hyun, M.K.; Kang, D.; Lee, S.; Park, C.; Moon, H.R.; Chung, H.Y. Evaluation of the novel synthetic tyrosinase inhibitor (Z)-3-(3-bromo-4-hydroxybenzylidene)thiochroman-4-one (MHY1498) in vitro and in silico. Molecules, 2018, 23(12), 12.
[http://dx.doi.org/10.3390/molecules23123307] [PMID: 30551624]
[3]
Lee, S.; Ullah, S.; Park, C.; Won Lee, H.; Kang, D.; Yang, J.; Akter, J.; Park, Y.; Chun, P.; Moon, H.R. Inhibitory effects of N-(acryloyl)benzamide derivatives on tyrosinase and melanogenesis. Bioorg. Med. Chem., 2019, 27(17), 3929-3937.
[http://dx.doi.org/10.1016/j.bmc.2019.07.034] [PMID: 31345746]
[4]
Jiménez, M.; Chazarra, S.; Escribano, J.; Cabanes, J.; García-Carmona, F. Competitive inhibition of mushroom tyrosinase by 4-substituted benzaldehydes. J. Agric. Food Chem., 2001, 49(8), 4060-4063.
[http://dx.doi.org/10.1021/jf010194h] [PMID: 11513710]
[5]
Yi, W.; Dubois, C.; Yahiaoui, S.; Haudecoeur, R.; Belle, C.; Song, H.; Hardré, R.; Réglier, M.; Boumendjel, A. Refinement of arylthiosemicarbazone pharmacophore in inhibition of mushroom tyrosinase. Eur. J. Med. Chem., 2011, 46(9), 4330-4335.
[http://dx.doi.org/10.1016/j.ejmech.2011.07.003] [PMID: 21777998]
[6]
Hałdys, K.; Goldeman, W.; Jewgiński, M.; Wolińska, E.; Anger, N.; Rossowska, J.; Latajka, R. Inhibitory properties of aromatic thiosemicarbazones on mushroom tyrosinase: Synthesis, kinetic studies, molecular docking and effectiveness in melanogenesis inhibition. Bioorg. Chem., 2018, 81, 577-586.
[http://dx.doi.org/10.1016/j.bioorg.2018.09.003] [PMID: 30248509]
[7]
Kim, J.Y.; Kim, J.Y.; Jenis, J.; Li, Z.P.; Ban, Y.J.; Baiseitova, A.; Park, K.H. Tyrosinase inhibitory study of flavonolignans from the seeds of Silybum marianum (Milk thistle). Bioorg. Med. Chem., 2019, 27(12), 2499-2507.
[http://dx.doi.org/10.1016/j.bmc.2019.03.013] [PMID: 30871862]
[8]
El-Naggar, N.E.; El-Ewasy, S.M. Bioproduction, characterization, anticancer and antioxidant activities of extracellular melanin pigment produced by newly isolated microbial cell factories Streptomyces glaucescens NEAE-H. Sci. Rep., 2017, 7, 42129.
[http://dx.doi.org/10.1038/srep42129] [PMID: 28195138]
[9]
Niu, C.; Yin, L.; Nie, L.F.; Dou, J.; Zhao, J.Y.; Li, G.; Aisa, H.A. Synthesis and bioactivity of novel isoxazole chalcone derivatives on tyrosinase and melanin synthesis in murine B16 cells for the treatment of vitiligo. Bioorg. Med. Chem., 2016, 24(21), 5440-5448.
[http://dx.doi.org/10.1016/j.bmc.2016.08.066] [PMID: 27622747]
[10]
Kim, Y.J.; Uyama, H. Tyrosinase inhibitors from natural and synthetic sources: Structure, inhibition mechanism and perspective for the future. Cell. Mol. Life Sci., 2005, 62(15), 1707-1723.
[http://dx.doi.org/10.1007/s00018-005-5054-y] [PMID: 15968468]
[11]
Ullah, S.; Kang, D.; Lee, S.; Ikram, M.; Park, C.; Park, Y.; Yoon, S.; Chun, P.; Moon, H.R. Synthesis of cinnamic amide derivatives and their anti-melanogenic effect in α-MSH-stimulated B16F10 melanoma cells. Eur. J. Med. Chem., 2019, 161, 78-92.
[http://dx.doi.org/10.1016/j.ejmech.2018.10.025] [PMID: 30347330]
[12]
Ferro, S.; De Luca, L.; Germanò, M.P.; Buemi, M.R.; Ielo, L.; Certo, G.; Kanteev, M.; Fishman, A.; Rapisarda, A.; Gitto, R. Chemical exploration of 4-(4-fluorobenzyl)piperidine fragment for the development of new tyrosinase inhibitors. Eur. J. Med. Chem., 2017, 125, 992-1001.
[http://dx.doi.org/10.1016/j.ejmech.2016.10.030] [PMID: 27810600]
[13]
Kim, C.S.; Noh, S.G.; Park, Y.; Kang, D.; Chun, P.; Chung, H.Y.; Jung, H.J.; Moon, H.R. A potent tyrosinase inhibitor, (E)-3-(2,4-Dihydroxyphenyl)-1-(thiophen-2-yl)prop-2-en-1-one, with anti-melanogenesis properties in α-MSH and IBMX-induced B16F10 melanoma cells. Molecules, 2018, 23(10), 2725.
[14]
Maeda, K.; Fukuda, M. Arbutin: Mechanism of its depigmenting action in human melanocyte culture. J. Pharmacol. Exp. Ther., 1996, 276(2), 765-769.
[PMID: 8632348]
[15]
Liu, X.X.; Sun, S.Q.; Wang, Y.J.; Xu, W.; Wang, Y.F.; Park, D.; Zhou, H.M.; Han, H.Y. Kinetics and computational docking studies on the inhibition of tyrosinase induced by oxymatrine. Appl. Biochem. Biotechnol., 2013, 169(1), 145-158.
[http://dx.doi.org/10.1007/s12010-012-9960-9] [PMID: 23160948]
[16]
Si, Y.X.; Yin, S.J.; Park, D.; Chung, H.Y.; Yan, L.; Lü, Z.R.; Zhou, H.M.; Yang, J.M.; Qian, G.Y.; Park, Y.D. Tyrosinase inhibition by isophthalic acid: kinetics and computational simulation. Int. J. Biol. Macromol., 2011, 48(4), 700-704.
[http://dx.doi.org/10.1016/j.ijbiomac.2011.02.015] [PMID: 21371502]
[17]
Si, Y.X.; Wang, Z.J.; Park, D.; Chung, H.Y.; Wang, S.F.; Yan, L.; Yang, J.M.; Qian, G.Y.; Yin, S.J.; Park, Y.D. Effect of hesperetin on tyrosinase: inhibition kinetics integrated computational simulation study. Int. J. Biol. Macromol., 2012, 50(1), 257-262.
[http://dx.doi.org/10.1016/j.ijbiomac.2011.11.001] [PMID: 22093614]
[18]
Lima, C.R.; Silva, J.R.; de Tássia Carvalho Cardoso, E.; Silva, E.O.; Lameira, J.; do Nascimento, J.L.; do Socorro Barros Brasil, D.; Alves, C.N. Combined kinetic studies and computational analysis on kojic acid analogous as tyrosinase inhibitors. Molecules, 2014, 19(7), 9591-9605.
[http://dx.doi.org/10.3390/molecules19079591] [PMID: 25004069]
[19]
Wang, Y.; Zhang, G.; Yan, J.; Gong, D. Inhibitory effect of morin on tyrosinase: insights from spectroscopic and molecular docking studies. Food Chem., 2014, 163, 226-233.
[http://dx.doi.org/10.1016/j.foodchem.2014.04.106] [PMID: 24912720]
[20]
Carvalho, M.; Hawksworth, G.; Milhazes, N.; Borges, F.; Monks, T.J.; Fernandes, E.; Carvalho, F.; Bastos, M.L. Role of metabolites in MDMA (ecstasy)-induced nephrotoxicity: An in vitro study using rat and human renal proximal tubular cells. Arch. Toxicol., 2002, 76(10), 581-588.
[http://dx.doi.org/10.1007/s00204-002-0381-3] [PMID: 12373454]
[21]
Jin, R.; Lou, B.; Lin, C. Tyrosinase-mediated in situ forming hydrogels from biodegradable chondroitin sulfate-tyramine conjugates. Polym. Int., 2013, 62(3), 353-361.
[http://dx.doi.org/10.1002/pi.4306]
[22]
Morris, G.M.; Huey, R.; Lindstrom, W.; Sanner, M.F.; Belew, R.K.; Goodsell, D.S.; Olson, A.J. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J. Comput. Chem., 2009, 30(16), 2785-2791.
[http://dx.doi.org/10.1002/jcc.21256] [PMID: 19399780]
[23]
Ismaya, W.T.; Rozeboom, H.J.; Weijn, A.; Mes, J.J.; Fusetti, F.; Wichers, H.J.; Dijkstra, B.W. Crystal structure of Agaricus bisporus mushroom tyrosinase: Identity of the tetramer subunits and interaction with tropolone. Biochemistry, 2011, 50(24), 5477-5486.
[http://dx.doi.org/10.1021/bi200395t] [PMID: 21598903]
[24]
Abuelizz, H.A.; Iwana, N.A.N.I.; Ahmad, R.; Anouar, E.H.; Marzouk, M.; Al-Salahi, R. Synthesis, biological activity and molecular docking of new tricyclic series as α-glucosidase inhibitors. BMC Chem, 2019, 13(1), 52.
[http://dx.doi.org/10.1186/s13065-019-0560-4] [PMID: 31384800]
[25]
Abuelizz, H.A.; Anouar, E.H.; Ahmad, R.; Azman, N.I.I.N.; Marzouk, M.; Al-Salahi, R. Triazoloquinazolines as a new class of potent α-glucosidase inhibitors: In vitro evaluation and docking study. PLoS One, 2019, 14(8) e0220379
[http://dx.doi.org/10.1371/journal.pone.0220379] [PMID: 31412050]
[26]
Abuelizz, H.A.; Taie, H.A.A.; Marzouk, M.; Al-Salahi, R. Synthesis and antioxidant activity of 2-methylthio-pyrido[3,2-e][1,2,4] triazolo[1,5-a]pyrimidines. Open Chem., 2019, 17, 823-830.
[http://dx.doi.org/10.1515/chem-2019-0092]

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