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Current Organic Synthesis

Author(s): Aref G. Ghahsare, Zahra S. Nazifi* and Seyed M.R. Nazifi*

DOI: 10.2174/1570179416666191017094908

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Structure-Bioactivity Relationship Study of Xanthene Derivatives: A Brief Review

Page: [1071 - 1077] Pages: 7

  • * (Excluding Mailing and Handling)

Abstract

Over the last decades, several heterocyclic derivatives compounds have been synthesized or extracted from natural resources and have been tested for their pharmaceutical activities. Xanthene is one of these heterocyclic derivatives. These compounds consist of an oxygen-containing central heterocyclic structure with two more cyclic structures fused to the central cyclic compound. It has been shown that xanthane derivatives are bioactive compounds with diverse activities such as anti-bacterial, anti-fungal, anti-cancer, and anti-inflammatory as well as therapeutic effects on diabetes and Alzheimer. The anti-cancer activity of such compounds has been one of the main research fields in pharmaceutical chemistry. Due to this diverse biological activity, xanthene core derivatives are still an attractive research field for both academia and industry. This review addresses the current finding on the biological activities of xanthene derivatives and discussed in detail some aspects of their structure-activity relationship (SAR).

Keywords: Xanthene, structure-activity relationship (SAR), biological activity, polycyclic, natural resources, pharmaceutical activities.

Graphical Abstract

[1]
Haritash, A.K.; Kaushik, C.P. Biodegradation aspects of polycyclic aromatic hydrocarbons (PAHs): A review. J. Hazard. Mater., 2009, 169(1-3), 1-15.
[http://dx.doi.org/10.1016/j.jhazmat.2009.03.137] [PMID: 19442441]
[2]
Kim, K-H.; Jahan, S.A.; Kabir, E.; Brown, R.J. A review of airborne polycyclic aromatic hydrocarbons (PAHs) and their human health effects. Environ. Int., 2013, 60, 71-80.
[http://dx.doi.org/10.1016/j.envint.2013.07.019] [PMID: 24013021]
[3]
Holme, J.A.; Brinchmann, B.C.; Refsnes, M.; Låg, M.; Øvrevik, J. Potential role of polycyclic aromatic hydrocarbons as mediators of cardiovascular effects from combustion particles. Environ. Health, 2019, 18(1), 74.
[http://dx.doi.org/10.1186/s12940-019-0514-2] [PMID: 31439044]
[4]
O’Riordan, W.; Green, S.; Overcash, J.S.; Puljiz, I.; Metallidis, S.; Gardovskis, J.; Garrity-Ryan, L.; Das, A.F.; Tzanis, E.; Eckburg, P.B.; Manley, A.; Villano, S.A.; Steenbergen, J.N.; Loh, E. Omadacycline for acute bacterial skin and skin-structure infections. N. Engl. J. Med., 2019, 380(6), 528-538.
[http://dx.doi.org/10.1056/NEJMoa1800170] [PMID: 30726689]
[5]
Li, Y.; Jiang, J-G. Health functions and structure-activity relationships of natural anthraquinones from plants. Food Funct., 2018, 9(12), 6063-6080.
[http://dx.doi.org/10.1039/C8FO01569D] [PMID: 30484455]
[6]
Shi, H.; Nagai, J.; Sakatsume, T.; Bandow, K.; Okudaira, N.; Uesawa, Y.; Sakagami, H.; Tomomura, M.; Tomomura, A.; Takao, K.; Sugita, Y. Quantitative structure–cytotoxicity relationship of 3-(N-cyclicamino) chromone derivatives. Anticancer Res., 2018, 38(8), 4459-4467.
[http://dx.doi.org/10.21873/anticanres.12748] [PMID: 30061210]
[7]
Samanta, S.K.; Singh, O.V.; Jain, R.K. Polycyclic aromatic hydrocarbons: Environmental pollution and bioremediation. Trends Biotechnol., 2002, 20(6), 243-248.
[http://dx.doi.org/10.1016/S0167-7799(02)01943-1] [PMID: 12007492]
[8]
Shimada, T. Xenobiotic-metabolizing enzymes involved in activation and detoxification of carcinogenic polycyclic aromatic hydrocarbons. Drug Metab. Pharmacokinet., 2006, 21(4), 257-276.
[http://dx.doi.org/10.2133/dmpk.21.257] [PMID: 16946553]
[9]
Li, X.; Song, Y.; Yao, S.; Bian, Y.; Gu, C.; Yang, X.; Wang, F.; Jiang, X. Can biochar and oxalic acid alleviate the toxicity stress caused by polycyclic aromatic hydrocarbons in soil microbial communities? Sci. Total Environ., 2019, 695 133879
[http://dx.doi.org/10.1016/j.scitotenv.2019.133879] [PMID: 31425980]
[10]
van Meteren, N.; Lagadic-Gossmann, D.; Chevanne, M.; Gallais, I.; Gobart, D.; Burel, A.; Bucher, S.; Grova, N.; Fromenty, B.; Appenzeller, B.M.R.; Chevance, S.; Gauffre, F.; Le Ferrec, E.; Sergent, O. Polycyclic aromatic hydrocarbons can trigger hepatocyte release of extracellular vesicles by various mechanisms of action depending on their affinity for the aryl hydrocarbon receptor. Toxicol. Sci., 2019, 171, 443-462.
[http://dx.doi.org/10.1093/toxsci/kfz157] [PMID: 31368503]
[11]
Dai, Y.; Huo, X.; Cheng, Z.; Wang, Q.; Zhang, Y.; Xu, X. Alterations in platelet indices link polycyclic aromatic hydrocarbons toxicity to low-grade inflammation in preschool children. Environ. Int., 2019, 131 105043
[http://dx.doi.org/10.1016/j.envint.2019.105043] [PMID: 31352259]
[12]
Shankarling, G.; Jarag, K. Laser dyes. Resonance, 2010, 15, 804-818.
[http://dx.doi.org/10.1007/s12045-010-0090-9]
[13]
Ahmad, M.; King, T.A.; Ko, D-K.; Cha, B.H.; Lee, J. Performance and photostability of xanthene and pyrromethene laser dyes in sol-gel phases. J. Phys. D Appl. Phys., 2002, 35, 1473.
[http://dx.doi.org/10.1088/0022-3727/35/13/303]
[14]
De, S.; Das, S.; Girigoswami, A. Environmental effects on the aggregation of some xanthene dyes used in lasers. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2005, 61(8), 1821-1833.
[http://dx.doi.org/10.1016/j.saa.2004.06.054] [PMID: 15863053]
[15]
Tabara, A.; Yamane, C.; Abe, M.; Seguchi, M. Adsorption of xanthene food additive dyes to cellulose granules. Cellulose, 2011, 18, 45-55.
[http://dx.doi.org/10.1007/s10570-010-9462-2]
[16]
Luck, H.; Wallnoefer, P.; Bach, H. Food additives and their mutagenic effect. VII. Testing of several xanthene dyes for their mutagenic effect on Escherichi coli. Pathol. Microbiol. (Basel), 1963, 26, 206-224.
[PMID: 13931480]
[17]
Waite, J.G.; Yousef, A.E. Enhanced inactivation of foodborne pathogenic and spoilage bacteria by FDandC Red No. 3 and other xanthene derivatives during ultrahigh pressure processing. J. Food Prot., 2008, 71, 1861-1867.
[18]
Guo, S-H.; Leng, T-H.; Wang, K.; Wang, C-Y.; Shen, Y-J.; Zhu, W-H. A colorimetric and turn-on NIR fluorescent probe based on xanthene system for sensitive detection of thiophenol and its application in bioimaging. Talanta, 2018, 185, 359-364.
[http://dx.doi.org/10.1016/j.talanta.2018.03.062] [PMID: 29759212]
[19]
Liu, J.; Chen, X.; Zhang, Y.; Gao, G.; Zhang, X.; Hou, S. A novel xanthene-based colorimetric and fluorescence probe for detection of H2S in living cells. J. Lumin., 2018, 204, 480-484.
[http://dx.doi.org/10.1016/j.jlumin.2018.08.053]
[20]
Qi, H.; Takano, H.; Kato, Y.; Wu, Q.; Ogata, C.; Zhu, B.; Murata, Y.; Nakamura, Y. Hydogen peroxide-dependent photocytotoxicity by phloxine B, a xanthene-type food colorant. BBA-Gen. Subjects, 2011, 1810, 704-712.
[http://dx.doi.org/10.1016/j.bbagen.2011.04.010] [PMID: 21565256]
[21]
Ebaston, T.M.; Rozovsky, A.; Zaporozhets, A.; Bazylevich, A.; Tuchinsky, H.; Marks, V.; Gellerman, G.; Patsenker, L.D. Peptide-driven targeted drug-delivery system comprising turn-on near-infrared fluorescent xanthene-cyanine reporter for real-time monitoring of drug release. ChemMedChem, 2019, 14, 1727-1734.
[http://dx.doi.org/10.1002/cmdc.201900464] [PMID: 31403246]
[22]
Guo, S-H.; Leng, T-H.; Wang, K.; Shen, Y-J.; Wang, C-Y. A near-infrared xanthene-based fluorescent probe for selective detection of hydrazine and its application in living cells. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2019, 223 117344
[http://dx.doi.org/10.1016/j.saa.2019.117344] [PMID: 31319274]
[23]
Wan, Y.; Li, Y.; Liao, Z.; Tang, Z.; Li, Y.; Zhao, Y.; Xiong, B. A new xanthene-based fluorescent probe with a red light emission for selectively detecting glutathione and imaging in living cells. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2019, 223 117265
[http://dx.doi.org/10.1016/j.saa.2019.117265] [PMID: 31234021]
[24]
Zhang, N.; Dong, B.; Kong, X.; Wang, C.; Song, W.; Lin, W. Development of a xanthene-based red-emissive fluorescent probe for visualizing h2o2 in living cells, tissues and animals. J. Fluoresc., 2018, 28(2), 681-687.
[http://dx.doi.org/10.1007/s10895-018-2231-6] [PMID: 29696451]
[25]
Weisz, A.; James, I.C.; Mazzola, E.P.; Ridge, C.D.; Ijames, C.F.; Markey, S.P. Identification of 1′,5′-naphthyridinophthalone and its quantification in the color additive D&C Yellow No. 10 (Quinoline Yellow) using high-performance liquid chromatography. Food Addit. Contam. Part A Chem. Anal. Control Expo. Risk Assess., 2018, 35(3), 439-447.
[http://dx.doi.org/10.1080/19440049.2017.1416183] [PMID: 29279012]
[26]
Weisz, A.; Milstein, S.R.; Scher, A.L.; Hepp, N.M. Colouring agents in cosmetics: regulatory aspects and analytical methods. Analysis of Cosmetic Products, 2nd ed; Elsevier: Amsterdam, The Netherlands, 2017.
[27]
Rasooly, R. Expanding the bactericidal action of the food color additive phloxine B to gram-negative bacteria. FEMS Immunol. Med. Microbiol., 2005, 45(2), 239-244.
[http://dx.doi.org/10.1016/j.femsim.2005.04.004] [PMID: 15949926]
[28]
Naeimi, H.; Nazifi, Z.S. A highly efficient nano-Fe3O4 encapsulated-silica particles bearing sulfonic acid groups as a solid acid catalyst for synthesis of 1,8-dioxo-octahydroxanthene derivatives. J. Nanopart. Res., 2013, 15, 2026.
[http://dx.doi.org/10.1007/s11051-013-2026-2] [PMID: 24307859]
[29]
Naeimi, H.; Nazifi, Z.S. Sulfonated diatomite as heterogeneous acidic nanoporous catalyst for synthesis of 14-aryl-14-H-dibenzo [a, j] xanthenes under green conditions. Appl. Catal. A Gen., 2014, 477, 132-140.
[http://dx.doi.org/10.1016/j.apcata.2014.03.012]
[30]
Naeimi, H.; Nazifi, Z.S. Environmentally benign and one-pot synthesis of 14-aryl-14H-dibenzo [a, j] xanthenes catalyzed by acyclic Brønsted acidic ionic liquid [H-NMP][HSO4] under green conditions. C. R. Chim., 2014, 17, 41-48.
[http://dx.doi.org/10.1016/j.crci.2013.08.003]
[31]
Naeimi, H.; Nazifi, Z.S. A facile one-pot ultrasound assisted synthesis of 1, 8-dioxo-octahydroxanthene derivatives catalyzed by Brønsted acidic ionic liquid (BAIL) under green conditions. J. Ind. Eng. Chem., 2014, 20, 1043-1049.
[http://dx.doi.org/10.1016/j.jiec.2013.06.041]
[32]
Naeimi, H.; Nazifi, Z.S. Convenient Synthesis of 14‐Aryl‐14‐H‐dibenzo [a, j] xanthenes Catalyzed by Acyclic Brønsted Acidic Ionic Liquid [H—NMP]+[HSO4]− under Microwave Irradiation. J. Chin. Chem. Soc. (Taipei), 2013, 60, 1113-1117.
[http://dx.doi.org/10.1002/jccs.201300019]
[33]
Srinivas Lavanya Kumar, M.; Singh, J.; Manna, S.K.; Maji, S.; Konwar, R.; Panda, G. Diversity oriented synthesis of chromene-xanthene hybrids as anti-breast cancer agents. Bioorg. Med. Chem. Lett., 2018, 28(4), 778-782.
[http://dx.doi.org/10.1016/j.bmcl.2017.12.065] [PMID: 29352645]
[34]
Wang, X-Z.; Yang, B-Y.; Lin, G-J.; Xie, Y-Y.; Huang, H-L.; Liu, Y-J. Cytotoxicity, cell cycle arrest, antioxidant activity and interaction of dibenzoxanthenes derivatives with DNA. DNA Cell Biol., 2012, 31(9), 1468-1474.
[http://dx.doi.org/10.1089/dna.2012.1726] [PMID: 22845759]
[35]
Jia, Z.; Yang, H-H.; Liu, Y-J.; Wang, X-Z. Novel ethanocycloheptono [3,4,5-kl]benzo[a]xanthene induces apoptosis in BEL-7402 cells. Mol. Cell. Biochem., 2018, 445(1-2), 145-156.
[http://dx.doi.org/10.1007/s11010-017-3260-1] [PMID: 29380241]
[36]
Giri, R.; Goodell, J.R.; Xing, C.; Benoit, A.; Kaur, H.; Hiasa, H.; Ferguson, D.M. Synthesis and cancer cell cytotoxicity of substituted xanthenes. Bioorg. Med. Chem., 2010, 18(4), 1456-1463.
[http://dx.doi.org/10.1016/j.bmc.2010.01.018] [PMID: 20129790]
[37]
Bhattacharya, A.K.; Rana, K.C.; Mujahid, M.; Sehar, I.; Saxena, A.K. Synthesis and in vitro study of 14-aryl-14H-dibenzo[a.j]xanthenes as cytotoxic agents. Bioorg. Med. Chem. Lett., 2009, 19(19), 5590-5593.
[http://dx.doi.org/10.1016/j.bmcl.2009.08.033] [PMID: 19717302]
[38]
Spatafora, C.; Barresi, V.; Bhusainahalli, V.M.; Di Micco, S.; Musso, N.; Riccio, R.; Bifulco, G.; Condorelli, D.; Tringali, C. Bio-inspired benzo[k,l]xanthene lignans: synthesis, DNA-interaction and antiproliferative properties. Org. Biomol. Chem., 2014, 12(17), 2686-2701.
[http://dx.doi.org/10.1039/c3ob42521e] [PMID: 24647864]
[39]
Di Micco, S.; Mazué, F.; Daquino, C.; Spatafora, C.; Delmas, D.; Latruffe, N.; Tringali, C.; Riccio, R.; Bifulco, G. Structural basis for the potential antitumour activity of DNA-interacting benzo[kl]xanthene lignans. Org. Biomol. Chem., 2011, 9(3), 701-710.
[http://dx.doi.org/10.1039/C0OB00480D] [PMID: 21079866]
[40]
Song, Y.; Yang, Y.; Wu, L.; Dong, N.; Gao, S.; Ji, H.; Du, X.; Liu, B.; Chen, G. Synthesis and cytotoxicity of N-substituted dibenzo[a,j]xanthene-3,11-dicarboxamide derivatives. Molecules, 2017, 22(4), 517.
[http://dx.doi.org/10.3390/molecules22040517] [PMID: 28333112]
[41]
Mihalyi, A.; Jamshidi, S.; Slikas, J.; Bugg, T.D. Identification of novel inhibitors of phospho-MurNAc-pentapeptide translocase MraY from library screening: Isoquinoline alkaloid michellamine B and xanthene dye phloxine B. Bioorg. Med. Chem., 2014, 22(17), 4566-4571.
[http://dx.doi.org/10.1016/j.bmc.2014.07.035] [PMID: 25127465]
[42]
Zawadzke, L.E.; Wu, P.; Cook, L.; Fan, L.; Casperson, M.; Kishnani, M.; Calambur, D.; Hofstead, S.J.; Padmanabha, R. Targeting the MraY and MurG bacterial enzymes for antimicrobial therapeutic intervention. Anal. Biochem., 2003, 314(2), 243-252.
[http://dx.doi.org/10.1016/S0003-2697(02)00622-X] [PMID: 12654311]
[43]
Epstein, O.; Bryan, M.C.; Cheng, A.C.; Derakhchan, K.; Dineen, T.A.; Hickman, D.; Hua, Z.; Human, J.B.; Kreiman, C.; Marx, I.E.; Weiss, M.M.; Wahl, R.C.; Wen, P.H.; Whittington, D.A.; Wood, S.; Zheng, X.M.; Fremeau, R.T., Jr; White, R.D.; Patel, V.F. Lead optimization and modulation of hERG activity in a series of aminooxazoline xanthene β-site amyloid precursor protein cleaving enzyme (BACE1) inhibitors. J. Med. Chem., 2014, 57(23), 9796-9810.
[http://dx.doi.org/10.1021/jm501266w] [PMID: 25389560]
[44]
Naya, A.; Sagara, Y.; Ohwaki, K.; Saeki, T.; Ichikawa, D.; Iwasawa, Y.; Noguchi, K.; Ohtake, N. Design, synthesis, and discovery of a novel CCR1 antagonist. J. Med. Chem., 2001, 44(9), 1429-1435.
[http://dx.doi.org/10.1021/jm0004244] [PMID: 11311066]
[45]
Kwon, Y.; Song, P.; Yoon, J.H.; Ghim, J.; Kim, D.; Kang, B.; Lee, T.G.; Kim, J-A.; Choi, J-K.; Youn, I.K.; Lee, H.K.; Ryu, S.H. Xanthene derivatives increase glucose utilization through activation of LKB1-dependent AMP-activated protein kinase. PLoS One, 2014, 9(9) e108771
[http://dx.doi.org/10.1371/journal.pone.0108771] [PMID: 25250787]
[46]
Miura, T.; Ichiki, H.; Hashimoto, I.; Iwamoto, N.; Kato, M.; Kubo, M.; Ishihara, E.; Komatsu, Y.; Okada, M.; Ishida, T.; Tanigawa, K. Antidiabetic activity of a xanthone compound, mangiferin. Phytomedicine, 2001, 8(2), 85-87.
[http://dx.doi.org/10.1078/0944-7113-00009] [PMID: 11315760]
[47]
Khurana, J.M.; Magoo, D.; Aggarwal, K.; Aggarwal, N.; Kumar, R.; Srivastava, C. Synthesis of novel 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-thiones and evaluation of their biocidal effects. Eur. J. Med. Chem., 2012, 58, 470-477.
[http://dx.doi.org/10.1016/j.ejmech.2012.10.025] [PMID: 23153816]