Calixarbutin: A Novel Calixarene-based Potential Water-soluble Anti-tyrosinase Agent with High Anti-melanoma Activity

Document Type : Research article

Authors

1 Deputy of Food and Drug Administration, Urmia University of Medical Sciences, Urmia, Iran.

2 Health Technology Incubation Center, Urmia University of Medical Sciences, Urmia, Iran.

Abstract

Since melanocytes are the origin of melanoma and some skin disorders such as melasma, they are important cells from the perspective of medicinal chemistry. Therefore, a medication that can simultaneously overcome these diseases will be a successful potential therapeutic agent. Arbutin with phenolic structure is a powerful natural anti-tyrosinase agent. Hence, the phenolic structure of this drug, prompted us to design its novel calix [4]arene-based cluster. Therefore, the present study reports the synthesis and in-vitro bio-activities of cyclic tetramer of arbutin in comparison to its simple drug unit as the reference medication. The in-vitro biological results showed amplified anti-tyrosinase (6-fold) and anti-melanoma (27-fold) activities, in addition to more aqueous solubility (8-fold) for this cluster in relation to arbutin. Therefore, compared to arbutin, more bioactive cluster can be considered as a novel water-soluble melanogenesis inhibitor with high anti-melanoma activity.

Graphical Abstract

Calixarbutin: A Novel Calixarene-based Potential Water-soluble Anti-tyrosinase Agent with High Anti-melanoma Activity

Keywords

Main Subjects


  • Nasuhi Pur F. Calixdrugs: calixarene-based clusters of established therapeutic drug agents. Divers. (2016) 20: 781 – 787.
  • Pillaiyar T, Manickam M and Namasivayam V. Skin whitening agents: medicinal chemistry perspective of tyrosinase inhibitors. Enzyme Inhib. Med. Chem. (2017) 32: 403-425.
  • Pillaiyar T, Namasivayam V, Manickam M and Jung SH. Inhibitors of Melanogenesis: An Updated Review. Med. Chem. (2018) 61: 7395-7418.
  • Zhu W and J. Gao J. The use of botanical extracts as topical skin-lightening agents for the improvement of skin pigmentation disorders. Investig. Dermatol. Symp. Proc. (2008) 13: 20-24.
  • Kang MJ, Ha HW, Kim GH, Lee SK, Ahn YT, Kim DH, Jeong HG and Jeong TC. Role of Metabolism by Intestinal Bacteria in Arbutin-Induced Suppression of Lymphoproliferative Response in vitro. Ther. (Seoul) (2012) 20: 196-200.
  • Hori I, Nihei K and Kubo I. Structural criteria for depigmenting mechanism of arbutin. Res. (2004) 18: 475-479.
  • Sugimoto K, Nishimura T, Nomura K, Sugimoto K and Kuriki T. Inhibitory effects of alpha-arbutin on melanin synthesis in cultured human melanoma cells and a three-dimensional human skin model. Pharm. Bull. (2004) 27: 510-514.
  • Nasuhi Pur F and Akbari Dilmaghani K. Calixplatin: novel potential anticancer agent based on the platinum complex with functionalized calixarene. Coord. Chem. (2014) 67: 440-448.
  • Nasuhi Pur F and Akbari Dilmaghani K. Calixpenams: synthesis, characterization, and biological evaluation of penicillins V and X clustered by calixarene scaffold. J. Chem. (2014) 38: 288-296.
  • Nasuhi Pur F and Akbari Dilmaghani K. Calixcephems: clustered cephalosporins analogous to calixpenams as novel potential anti-MRSA agents. J. Chem. (2014) 38: 850-858.
  • Nasuhi Pur F and Akbari Dilmaghani K. Calixtyrosol: a novel calixarene based potent radical scavenger. J. Pharm. Res. (2015) 14: 1181 – 1187.
  • Nasuhi Pur F and Akbari Dilmaghani K. New antiradical clusters synthesized using the first green Biginelli reactions of calix[4]Arene. Chem. J. (2016) 50: 80 – 82.
  • Delnavaz Shahr A, Nasuhi Pur F and Akbari Dilmaghani K. Calixapap: calixarene-based cluster of acetaminophen as a novel antiradical agent. J. Pharm. Res. (2019) 18: 30 – 33.
  • Nasuhi Pur F, Delnavaz Shahr A and Akbari Dilmaghani K. Calixmexitil: calixarene-based cluster of mexiletine with amplified anti-myotonic activity as a novel use-dependent sodium channel blocker. J. Pharm. Res. (2019) 18: 1351-1357.
  • Nihei K and Kubo I. Identification of oxidation product of arbutin in mushroom tyrosinase assay system. Med. Chem. Lett. (2003) 13: 2409-2412.
  • Jaime C, de Mendoza J, Prados P, Nieto PM and Sanchez C. Carbon-13 NMR chemical shifts. A single rule to determine the conformation of calix[4]arenes. Org. Chem. (1991) 56: 3372–3376.
  • Redemann CE and Niemann C. 2, 3, 4, 6-Tetraacetyl-α-d-gluco-pyranosyl bromide. Synth. (1942) 22.
  • Song YM, Ha YM, Kim JA, Chung KW, Uehara Y, Lee KJ, Chun P, Byun Y, Chung HY and Moon HR. Synthesis of novel azo-resveratrol, azo-oxyresveratrol and their derivatives as potent tyrosinase inhibitors. Med. Chem. Lett. (2012) 22: 7451-7455.