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Review

Xanthones as P-glycoprotein modulators and their impact on drug bioavailability

, , , , , & show all
Pages 441-482 | Received 22 Aug 2020, Accepted 03 Dec 2020, Published online: 20 Apr 2021

References

  • Silva R, Vilas-Boas V, Carmo H, et al., Modulation of P-glycoprotein efflux pump: induction and activation as a therapeutic strategy. Pharmacol Ther. 149(p): 1–123. 2015b.
  • Juliano RL, Ling V. A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim Biophys Acta. 1976;455(1):152–62.
  • Aller SG, Yu J, Ward A, et al. Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding. Science. 2009;323(5922):1718–22.
  • Hennessy M, Spiers JP. A primer on the mechanics of P-glycoprotein the multidrug transporter. Pharmacol Res. 2007;55(1):1–15.
  • Sharom FJ, Sharom FJ. The P-glycoprotein multidrug transporter. Essays Biochem. 2011;50(1):161–78.
  • Zhou S-F. Structure, function and regulation of P-glycoprotein and its clinical relevance in drug disposition. Xenobiotica. 2008;38(7–8):802–32.
  • Mo W, Zhang JT. Human ABCG2: structure, function, and its role in multidrug resistance. Int J Biochem Mol Biol. 2012;3(1):1–27.
  • Ambudkar SV, Kimchi-Sarfaty C, Sauna ZE, et al. P-glycoprotein: from genomics to mechanism. Oncogene. 2003;22(47):7468–85.
  • Amin ML. P-glycoprotein Inhibition for Optimal Drug Delivery. Drug Target Insights. 2013;7(p):27–34.
  • Sajid A, Lusvarghi S, Chufan EE, et al. Evidence for the critical role of transmembrane helices 1 and 7 in substrate transport by human P-glycoprotein (ABCB1). PLoS One. 2018;13(9):e0204693.
  • Linton KJ. Structure and function of ABC transporters. Physiology (Bethesda). 2007;22(p):122–130.
  • Vasiliou V, Vasiliou K, Nebert DW. Human ATP-binding cassette (ABC) transporter family. Hum Genomics. 2008;3(3):281–90.
  • Ito K, Suzuki H, Horie T, et al. Apical/basolateral surface expression of drug transporters and its role in vectorial drug transport. Pharm Res. 2005;22(10):1559–77.
  • DeGorter MK, Xia CQ, Yang JJ, et al. Drug transporters in drug efficacy and toxicity. Annu Rev Pharmacol Toxicol. 2012;52(1):249–273.
  • Zamek-Gliszczynski MJ, Hoffmaster KA, Tweedie DJ, et al. Highlights from the International Transporter Consortium second workshop. Clin Pharmacol Ther. 2012;92(5):553–6.
  • Gameiro M, Silva R, Rocha-Pereira C, et al. Cellular Models and In Vitro Assays for the Screening of modulators of P-gp, MRP1 and BCRP. Molecules. 2017;22(4):4.
  • Doring B, Petzinger E. Phase 0 and phase III transport in various organs: combined concept of phases in xenobiotic transport and metabolism. Drug Metab Rev. 2014;46(3):261–82.
  • Zhou S-F, Wang -L-L, Di Y, et al. Substrates and inhibitors of human multidrug resistance associated proteins and the implications in drug development. Curr Med Chem. 2008;15(20):1981–2039.
  • Ghanem CI, Arias A, Novak A, et al. Acetaminophen-induced stimulation of MDR1 expression and activity in rat intestine and in LS 174T human intestinal cell line. Biochem Pharmacol. 2011;81(2):244–50.
  • Doherty MM, Charman WN. The mucosa of the small intestine: how clinically relevant as an organ of drug metabolism? Clin Pharmacokinet. 2002;41(4):235–53.
  • Schinkel AH. P-Glycoprotein, a gatekeeper in the blood–brain barrier. Adv Drug Deliv Rev. 1999;36(2–3):179–194.
  • Gil-Martins E, Barbosa DJ, Silva V, et al. Dysfunction of ABC transporters at the blood-brain barrier: role in neurological disorders. Pharmacol Ther. 2020;213:107554.
  • de Lange EC. Potential role of ABC transporters as a detoxification system at the blood?CSF barrier. Adv Drug Deliv Rev. 2004;56(12):1793–809.
  • Deeley RG, Westlake C, Cole SP. Transmembrane transport of endo- and xenobiotics by mammalian ATP-binding cassette multidrug resistance proteins. Physiol Rev. 2006;86(3):849–99.
  • Ridano ME, Racca AC, Flores-Martin JB, et al. Impact of chlorpyrifos on human villous trophoblasts and chorionic villi. Toxicol Appl Pharmacol. 2017;329(p):26–39.
  • Gil S, Saura R, Forestier F, et al. P-glycoprotein expression of the human placenta during pregnancy. Placenta. 2005;26(2–3):268–70.
  • Frank MH, Denton MD, Alexander SI, et al. Specific MDR1 P-glycoprotein blockade inhibits human alloimmune T cell activation in vitro. J Immunol. 2001;166(4):2451–9.
  • Silva R, Palmeira A, Carmo H, et al. P-glycoprotein induction in Caco-2 cells by newly synthetized thioxanthones prevents paraquat cytotoxicity. Arch Toxicol. 2015a;89(10):1783–800.
  • Robey RW, Pluchino KM, Hall MD, et al. Revisiting the role of ABC transporters in multidrug-resistant cancer. Nat Rev Cancer. 2018;18(7):452–464.
  • Tamaki A, Lerano C, Szakacs G, et al. The controversial role of ABC transporters in clinical oncology. Essays Biochem. 2011;50(1):209–232.
  • Fromm MF. Importance of P-glycoprotein at blood–tissue barriers. Trends Pharmacol Sci. 2004;25(8):423–9.
  • Raggers RJ, Vogels I, van Meer G. Multidrug-resistance P-glycoprotein (MDR1) secretes platelet-activating factor. Biochem J. 2001;357(3):859–65.
  • Sharom FJ. ABC multidrug transporters: structure, function and role in chemoresistance. Pharmacogenomics. 2008;9(1):105–27.
  • Zhang J, Sun T, Liang L, et al. Drug promiscuity of P-glycoprotein and its mechanism of interaction with paclitaxel and doxorubicin. Soft Matter. 2014;10(3):438–45.
  • Palmeira A, Sousa E, H. Vasconcelos M, et al. Three decades of P-gp inhibitors: skimming through several generations and scaffolds. Curr Med Chem. 2012;19(13):1946–2025.
  • Silva R, Carmo H, Dinis-Oliveira R, et al. In vitro study of P-glycoprotein induction as an antidotal pathway to prevent cytotoxicity in Caco-2 cells. Arch Toxicol. 2011;85(4):315–26.
  • Silva R, Carmo H, Vilas-Boas V, et al. Colchicine effect on P-glycoprotein expression and activity: in silico and in vitro studies. Chem Biol Interact. 2014;218(p):50–62.
  • Rocha-Pereira C, Ghanem CI, Silva R, et al. P-glycoprotein activation by 1-(propan-2-ylamino)-4-propoxy-9H-thioxanthen-9-one (TX5) in rat distal ileum: ex vivo and in vivo studies. Toxicol Appl Pharmacol. 2020;386(p):114832.
  • Martins E, Silva V, Lemos A, et al., Newly synthesized oxygenated xanthones as potential p-glycoprotein activators: in vitro, ex vivo, and in silico studies. Molecules. 24(4): 707. 2019. .
  • Varma MV, Ashokraj Y, Dey CS, et al. P-glycoprotein inhibitors and their screening: a perspective from bioavailability enhancement. Pharmacol Res. 2003;48(4):347–59. .
  • Scotto KW. Transcriptional regulation of ABC drug transporters. Oncogene. 2003;22(47):7496–511.
  • Silva R, Sousa E, Carmo H, et al., Induction and activation of P-glycoprotein by dihydroxylated xanthones protect against the cytotoxicity of the P-glycoprotein substrate paraquat. Arch Toxicol. 88(4): 937–51. 2014. .
  • Sterz K, Möllmann L, Jacobs A, et al. Activators of P-glycoprotein: structure-activity relationships and investigation of their mode of action. ChemMedChem. 2009;4(11):1897–911.
  • Vilas-Boas V, Silva R, Palmeira A, et al. Development of novel rifampicin-derived P-glycoprotein activators/inducers. synthesis, in silico analysis and application in the RBE4 cell model, using paraquat as substrate. PLoS One. 2013;8(8):e74425.
  • Shapiro AB, Ling V. Positively cooperative sites for drug transport by P-glycoprotein with distinct drug specificities. Eur J Biochem. 1997;250(1):130–7.
  • Shapiro AB, Fox K, Lam P, et al. Stimulation of P-glycoprotein-mediated drug transport by prazosin and progesterone. Evidence for a third drug-binding site. Eur J Biochem. 1999;259(3):841–50.
  • Martin C, Berridge G, Higgins CF, et al. Communication between multiple drug binding sites on P-glycoprotein. Mol Pharmacol. 2000;58(3):624–32.
  • Vilas-Boas V, Silva R, Nunes C, et al. Mechanisms of P-gp inhibition and effects on membrane fluidity of a new rifampicin derivative, 1,8-dibenzoyl-rifampicin. Toxicol Lett. 2013;220(3):259–266.
  • Gomes AS, Brandão P, Sofia Garcia Fernandes C, et al. Drug-like properties and ADME of xanthone derivatives: the antechamber of clinical trials. Curr Med Chem. 2016;23(32):3654–3686.
  • Ahmad I, Shagufta. Recent insight into the biological activities of synthetic xanthone derivatives. Eur J Med Chem. 2016;116(p):267–280.
  • Luo C-T, Mao -S-S, Liu F-L, et al. Antioxidant xanthones from Swertia mussotii, a high altitude plant. Fitoterapia. 2013;91(p):140–147.
  • Pinto MM, Sousa ME, Nascimento MS. Xanthone derivatives: new insights in biological activities. Curr Med Chem. 2005;12(21):2517–38.
  • Resende D, Durães F, Maia M, et al. Recent advances in the synthesis of xanthones and azaxanthones. Org Chem Front. 2020;7(19):3027–3066.
  • Resende D, Pereira-Terra P, Moreira J, et al. Synthesis of a small library of nature-inspired xanthones and study of their antimicrobial activity. Molecules. 2020;25(10):10.
  • Lesch B, Brase S. A short, atom-economical entry to tetrahydroxanthenones. Angew Chem Int Ed Engl. 2004;43(1):115–8.
  • Masters K-S, Brase S. Xanthones from fungi, lichens, and bacteria: the natural products and their synthesis. Chem Rev. 2012;112(7):3717–76.
  • Ruan J, Zheng C, Liu Y, et al. Chemical and biological research on herbal medicines rich in xanthones. Molecules. 2017;22:10.
  • Yang C-H, Ma L, WEI Z-P, et al. Advances in isolation and synthesis of xanthone derivatives. Chinese Herbal Medicines. 2012;4(2):87–102.
  • Fernandes C, Oliveira L, Tiritan ME, et al. Synthesis of new chiral xanthone derivatives acting as nerve conduction blockers in the rat sciatic nerve. Eur J Med Chem. 2012;55(p):1–11.
  • Negi JS, Bisht VKB,P, Singh P, et al. Naturally Occurring Xanthones: chemistry and Biology. J Appl Chem. 2013;2013:1–9. [ 2013].
  • Vieira LM, Kijjoa A. Naturally-occurring xanthones: recent developments. Curr Med Chem. 2005;12(21):2413–46.
  • Roberts JC. Naturally Occurring Xanthones.. Chem Rev. 1961;61(6):591–605.
  • Klein‐Júnior LC, Campos A, Niero R, et al. Xanthones and Cancer: from Natural Sources to Mechanisms of Action. Chem Biodivers. 2020;17(2):e1900499.
  • Azevedo C, Afonso C, Pinto M. Routes to Xanthones: an Update on the Synthetic Approaches. <![CDATA[Current Organic Chemistry]]>. 2012;16(23):2818–2867.
  • Sousa ME, Pinto MM. Synthesis of xanthones: an overview. Curr Med Chem. 2005;12(21):2447–79.
  • Azevedo CM, Afonso C, Pinto M. Magalhaes, and madalena maria magalhaes, routes to xanthones: an update on the synthetic approaches. Curr Org Chem. 2012;16(23):2818–2867.
  • Negi JS, Bisht VK, Singh P, et al. Naturally occurring xanthones: chemistry and biology. J Appl Chem. 2013; 2013:621459.
  • Francik R, Szkaradek N, Zelaszczyk D, et al. ANTIOXIDANT ACTIVITY OF XANTHONE DERIVATIVES. Acta Pol Pharm. 2016;73(6):1505–1509.
  • Jung H-A, Su B-N, Keller WJ, et al. Antioxidant xanthones from the pericarp of garcinia mangostana (Mangosteen). J Agric Food Chem. 2006;54(6):2077–82.
  • Cidade H, Rocha V, Palmeira A, et al. In silico and in vitro antioxidant and cytotoxicity evaluation of oxygenated xanthone derivatives. Arabian J Chem. 2020;13(1):17–26.
  • Cheng Y-W, Kang -J-J. Mechanism of vasorelaxation of thoracic aorta caused by xanthone. Eur J Pharmacol. 1997;336(1):23–28.
  • Marona H, Librowski T, Cegla M, et al. Antiarrhythmic and antihypertensive activity of some xanthone derivatives. Acta Pol Pharm. 2008;65(3):383–90.
  • Rajtar G, Zolkowska D, Kleinrok Z, et al. Antiplatelets activity of some xanthone derivatives. Acta Pol Pharm. 1999;56(4):319–24.
  • Pfister JR, Ferraresi RW, Harrison IT, et al. Xanthone-2-carboxylic acids, a new series of antiallergic substances. J Med Chem. 1972;15(10):1032–1035.
  • Chen L-G, Yang -L-L, Wang -C-C. Anti-inflammatory activity of mangostins from Garcinia mangostana. Food Chem Toxicol. 2008;46(2):688–93.
  • Marona H, Szkaradek N, Karczewska E, et al. Antifungal and antibacterial activity of the newly synthesized 2-xanthone derivatives. Arch Pharm (Weinheim). 2009;342(1):9–18.
  • Yasunaka K, Abe F, Nagayama A, et al. Antibacterial activity of crude extracts from Mexican medicinal plants and purified coumarins and xanthones. J Ethnopharmacol. 2005;97(2):293–9.
  • Nguemeving JR, Azebaze AGB, Kuete V, et al. Laurentixanthones A and B, antimicrobial xanthones from Vismia laurentii. Phytochemistry. 2006;67(13):1341–6.
  • Fukai T, Yonekawa M, Hou A-J, et al. Antifungal agents from the roots of cudrania c ochinchinensis against candida, cryptococcus, and aspergillus species. J Nat Prod. 2003;66(8):1118–1120.
  • Feussi Tala M, Krohn K, Hussain H, et al. Laurentixanthone C: a new antifungal and algicidal xanthone from stem bark of vismia laurentii. Zeitschrift für Naturforschung B. 2007;62:565–568.
  • Reutrakul V, Anantachoke N, Pohmakotr M, et al. Cytotoxic and anti-HIV-1 caged xanthones from the resin and fruits of garcinia hanburyi. Planta Med. 2006;73(1):33–40.
  • Groweiss A, Cardellina JH, Boyd MR. HIV-inhibitory prenylated xanthones and flavones from maclura t inctoria 1. J Nat Prod. 2000;63(11):1537–9.
  • Xu Z, Huang L, Chen X-H, et al. Cytotoxic prenylated xanthones from the pericarps of garcinia mangostana. Molecules. 2014;19(2):1820–7.
  • Seesom W, Jaratrungtawee A, Suksamrarn S, et al. Antileptospiral activity of xanthones from Garcinia mangostanaand synergy of gamma-mangostin with penicillin G. BMC Complement Altern Med. 2013;13(1): 182–182. 10.1186/1472-6882-13-182.
  • Al-Massarani SM, El Gamal A, Al-Musayeib N, et al. Phytochemical, antimicrobial and antiprotozoal evaluation of garcinia mangostana pericarp and α-Mangostin, its major xanthone derivative. Molecules. 2013;18(9):10599–608.
  • Wu Y-P, Zhao W, Xia Z-Y, et al. Three novel xanthones from garcinia paucinervis and their anti-TMV activity. Molecules. 2013;18(8):9663–9669.
  • Gnerre C, Thull U, Gaillard P, et al. Natural and synthetic xanthones as monoamine oxidase inhibitors: biological assay and 3D-QSAR. Helvetica Chimica Acta. 2001;84(3):552–570.
  • Iikubo K, Ishikawa Y, Ando N, et al. The first direct synthesis of α-mangostin, a potent inhibitor of the acidic sphingomyelinase. Tetrahedron Lett. 2002;43(2):291–293.
  • Szkaradek N, Rapacz A, Pytka K, et al. Cardiovascular activity of the chiral xanthone derivatives. Bioorg Med Chem. 2015;23(20):6714–24.
  • Lemos A, Gomes AS, Loureiro JB, et al. Synthesis, biological evaluation, and in silico studies of novel aminated xanthones as potential p53-activating agents. Molecules. 2019;24(10):1975.
  • Gomes S, Raimundo L, Soares J, et al. New inhibitor of the TAp73 interaction with MDM2 and mutant p53 with promising antitumor activity against neuroblastoma. Cancer Lett. 2019;446(p):90–102.
  • Almeida JR, Palmeira A, Campos A, et al. Structure-Antifouling Activity Relationship and Molecular Targets of Bio-Inspired(thio)xanthones. Biomolecules. 2020;10(8):1126.
  • Resende DISP, Almeida MC, Maciel B, et al. Efficacy, stability, and safety evaluation of new polyphenolic xanthones towards identification of bioactive compounds to fight skin photoaging. Molecules. 2020;25(12):2782.
  • Silva V, Cerqueira F, Nazareth N, et al. 1,2-Dihydroxyxanthone: effect on A375-C5 melanoma cell growth associated with interference with THP-1 human macrophage activity. Pharm (Basel). 2019;12(2):2.
  • Rawat B, Singh P, Negi JS. Chemical constituents and biological importance of Swertia: a review. Cur Res Chem. 2011;3(p):1–15.
  • Jagetia GC, Venkatesha VA. Mangiferin, a glucosylxanthone, protects against the radiation-induced micronuclei formation in the cultured human peripheral blood lymphocytes. Int Congress Series. 2005;1276(p):195–196.
  • Leiro J, Arranz JA, Yáñez M, et al. Expression profiles of genes involved in the mouse nuclear factor-kappa B signal transduction pathway are modulated by mangiferin. Int Immunopharmacol. 2004;4(6):763–78.
  • Jastrzebska-Wiesek M, Czarnecki R, Marona H. The anticonvulsant, local anesthetic and hemodynamic properties of some chiral aminobutanol derivatives of xanthone. Acta Pol Pharm. 2008;65(5):591–600.
  • Ali M, Latif A, Zaman K, et al. Anti-ulcer xanthones from the roots of hypericum oblongifolium wall. Fitoterapia. 2014;95(p):258–265.
  • Li H, MIYAHARA T, TEZUKA Y, et al. The effect of kampo formulae on bone resorption in vitro and in vivo. I. Active constituents of Tsu-kan-gan. Biol Pharm Bull. 1998;21(12):1322–1326.
  • Perrucci S, Fichi G, Buggiani C, et al. Efficacy of mangiferin against Cryptosporidium parvum in a neonatal mouse model. Parasitol Res. 2006;99(2):184–8.
  • Ryu HW, Curtis-Long MJ, Jung S, et al. Xanthones with neuraminidase inhibitory activity from the seedcases of Garcinia mangostana. Bioorg Med Chem. 2010;18(17):6258–64.
  • Riscoe MV, Winter RW, Ignatushchenko M. Xanthones as antimalarial agents: stage specificity. Am J Trop Med Hyg. 2000;62(1):77–81.
  • Quan G-H, Oh S-R, Kim J-H, et al. Xanthone constituents of the fruits of garcinia mangostana with anticomplement activity. Phytother Res. 2010;24(10):1575–1577.
  • Shan T, Ma Q, Guo K, et al. Xanthones from mangosteen extracts as natural chemopreventive agents: potential anticancer drugs. Curr Mol Med. 2011;11(8):666–77.
  • Estudante M, Morais JG, Soveral G, et al. Intestinal drug transporters: an overview. Adv Drug Deliv Rev. 2013;65(10):1340–56.
  • Thiebaut F, Tsuruo T, Hamada H, et al. Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues. Proc Natl Acad Sci U S A. 1987;84(21):7735–8.
  • Chen P, Chen H, Zang X, et al. Expression of efflux transporters in human ocular tissues. Drug Metab Dispos. 2013;41(11):1934–48.
  • Carey SS, Gleason-Guzman M, Gokhale V, et al. Psorospermin structural requirements for P-glycoprotein resistance reversal. Mol Cancer Ther. 2008;7(11):3617–3623.
  • Chae SW, Lee J, Park JH, et al. Intestinal P-glycoprotein inhibitors, Benzoxanthone Analogues. J Pharm Pharmacol. 2018;70(2):234–241.
  • Chieli E, Romiti N, Rodeiro I, et al. In vitro effects of Mangifera indica and polyphenols derived on ABCB1/P-glycoprotein activity. Food Chem Toxicol. 2009;47(11):2703–2710.
  • Chieli E, Romiti N, Rodeiro I, et al. In vitro modulation of ABCB1/P-glycoprotein expression by polyphenols from Mangifera indica. Chem Biol Interact. 2010;186(3):287–294.
  • Kaewpiboon C, Boonnak N, Yawut N, et al. Caged-xanthone from Cratoxylum formosum sspruniflorum inhibits malignant cancer phenotypes in multidrug-resistant human A549 lung cancer cells through down-regulation of NF-κB. Bioorg Med Chem. 2019;27(12):2368–2375.
  • Louisa M, Soediro TM, Suyatna FD. In vitro modulation of P-glycoprotein, MRP-1 and BCRP expression by mangiferin in doxorubicin-treated MCF-7 cells. Asian Pac J Cancer Prev. 2014;15(4):1639–42.
  • Tolosa L, Rodeiro I, Donato MT, et al. Multiparametric evaluation of the cytoprotective effect of the Mangifera indica L. Stem Bark Extract and Mangiferin in HepG2 Cells. J Pharm Pharmacol. 2013;65(7):1073–1082.
  • Wang L-H, Yang J-Y, Yang S-N, et al. Suppression of NF-κB signaling and p-glycoprotein function by gambogic acid synergistically potentiates adriamycin -induced apoptosis in lung cancer. Curr Cancer Drug Targets. 2014;14(1):91–103.
  • Wang S, Wang L, Chen M, et al. Gambogic acid sensitizes resistant breast cancer cells to doxorubicin through inhibiting P-glycoprotein and suppressing survivin expression. Chem Biol Interact. 2015;235(p):76–84.
  • Wang S, Yang Y, Wang Y, et al. Gambogic acid-loaded pH-sensitive mixed micelles for overcoming breast cancer resistance. Int J Pharm. 2015;495(2):840–848.
  • Wang X, Deng R, Lu Y, et al. Gambogic acid as a non-competitive inhibitor of ATP-binding cassette transporter B1 reverses the multidrug resistance of human epithelial cancers by promoting ATP-binding cassette transporter B1 protein degradation. Basic Clin Pharmacol Toxicol. 2013;112(1):25–33.
  • Zhou Y, Wang R, Chen B, et al. Daunorubicin and gambogic acid coloaded cysteamine-CdTe quantum dots minimizing the multidrug resistance of lymphoma in vitro and in vivo. Int J Nanomed. 2016;11(p):5429–5442.
  • Palmeira A, Vasconcelos MH, Paiva A, et al. Dual inhibitors of P-glycoprotein and tumor cell growth: (Re)discovering thioxanthones. Biochem Pharmacol. 2012;83(1):57–68.
  • Huang J, Zhu X, Wang H, et al. Role of gambogic acid and NaI131 in A549/DDP cells. Oncol Lett. 2017;13(1):37–44.
  • Sousa E, Palmeira A, Cordeiro AS, et al. Bioactive xanthones with effect on P-glycoprotein and prediction of intestinal absorption. Med Chem Res. 2013;22(5):2115–2123.
  • Tian F, Dahmani FZ, Qiao J, et al. A targeted nanoplatform co-delivering chemotherapeutic and antiangiogenic drugs as a tool to reverse multidrug resistance in breast cancer. Acta Biomater. 2018;75(p):398–412.
  • Xu Q, Guo J, Chen W. Gambogenic acid reverses P-glycoprotein mediated multidrug resistance in HepG2/Adr cells and its underlying mechanism. Biochem Biophys Res Commun. 2019;508(3):882–888.
  • Tchamo DN, Dijoux-Franca M-G, Mariotte A-M, et al. Prenylated xanthones as potential P-glycoprotein modulators. Bioorg Med Chem Lett. 2000;10(12):1343–5.
  • Ye D, Zhou X, Pan H, et al. Establishment and characterization of an HPV16 E6/E7-expressing oral squamous cell carcinoma cell line with enhanced tumorigenicity. Med Oncol. 2011;28(4):1331–1337.
  • Paiva AM, Sousa ME, Camões A, et al. Prenylated xanthones: antiproliferative effects and enhancement of the growth inhibitory action of 4-hydroxytamoxifen in estrogen receptor-positive breast cancer cell line. Med Chem Res. 2012;21(5):552–558.
  • Pedro M, Cerqueira F, Sousa ME, et al. Xanthones as inhibitors of growth of human cancer cell lines and Their effects on the proliferation of human lymphocytes In Vitro. Bioorg Med Chem. 2002;10(12):3725–3730.
  • Sousa E, Silva A, Pinto M, et al. Isomeric Kielcorins and Dihydroxyxanthones: synthesis, Structure Elucidation, and Inhibitory Activities of Growth of Human Cancer Cell Lines and on the Proliferation of Human Lymphocytes In Vitro. Helvetica Chimica Acta. 2002;85(9):2862–2876.
  • Palmeira A, Paiva A, Sousa E, et al. Insights into the In Vitro Antitumor Mechanism of Action of a New Pyranoxanthone. Chem Biol Drug Des. 2010;76(1):43–58.
  • Kim HG, Hien TT, Han EH, et al. Metformin inhibits P-glycoprotein expression via the NF-κB pathway and CRE transcriptional activity through AMPK activation. Br J Pharmacol. 2011;162(5):1096–1108.
  • Sun J, Yeung CA, Co NN, et al. Clitocine reversal of P-glycoprotein associated multi-drug resistance through down-regulation of transcription factor NF-κB in R-HEPG2 cell line. Plos One. 2012;7(8):e40720.
  • Silva V, Gil-Martins E, Rocha-Pereira C, et al. Oxygenated xanthones as P-glycoprotein modulators at the intestinal barrier: in vitro and docking studies. Med Chem Res. 2020;29(6):1041–1057.
  • Boonyong C, Pattamadilok C, Suttisri R, et al. Benzophenones and xanthone derivatives from Garcinia schomburgkiana -induced P-glycoprotein overexpression in human colorectal Caco-2 cells via oxidative stress-mediated mechanisms. Phytomedicine. 2017;27(p):8–14.
  • Paiva AM, Pinto MM, Sousa E. A Century of Thioxanthones: through Synthesis and Biological Applications. <![CDATA[Current Medicinal Chemistry]]>. 2013;20(19):2438–2457.
  • Hageman HJ. Photoinitiators for free radical polymerization. Prog Org Coat. 1985;13(2):123–150.
  • Yilmaz G, Tuzun A, Yagci Y. Thioxanthone–carbazole as a Visible Light Photoinitiator for Free Radical Polymerization. Journal of Applied Chemistry. 2010;48(22):5120–5125.
  • Archer S, Pica-Mattoccia L, Cioli D, et al. The preparation, antischistosomal and antitumor activity of hycanthone and some of its congeners. Evidence for the mode of action of hycanthone. J Med Chem. 1988;31(1):254–260.
  • Bessa LJ, Palmeira A, Gomes AS, et al. Synergistic effects between thioxanthones and oxacillin against methicillin-resistant staphylococcus aureus. Microb Drug Resist. 2015;21(4):404–15.
  • Harfenist M, Joseph DM, Spence SC, et al. selective inhibitors of monoamine oxidase. 4. 1 SAR of Tricyclic N -methylcarboxamides and congeners binding at the tricyclics’ hydrophilic binding site. J Med Chem. 1997;40(16):2466–73.
  • Woo S-W, Kang D-H, Kim J-S, et al. Synthesis, Cytotoxicity and Topoisomerase II Inhibition Study of New Thioxanthone Analogues. Bull Korean Chem Soc. 2008;29(p):471–474.
  • Kostakis IK, Pouli N, Marakos P, et al. Synthesis, cytotoxic activity, NMR study and stereochemical effects of some new pyrano[3,2- b]thioxanthen-6-ones and Pyrano[2,3- c]thioxanthen-7-ones. Bioorg Med Chem. 2001;9(11):2793–2802.
  • Palmeira A, Sousa ME, Fernandes MX, et al. Multidrug resistance reversal effects of aminated thioxanthones and interaction with cytochrome P450 3A4. J Pharm Pharm Sci. 2011;15(1):31–45.
  • Del Rowe JD, Bello J, Mitnick R, et al. Accelerated regression of brain metastases in patients receiving whole brain radiation and the topoisomerase II inhibitor, lucanthone. Int J Radiat Oncol Biol Phys. 1999;43(1):89–93.
  • Mendez F, Goldman J, Bases R. Abasic Sites in DNA of HeLa Cells Induced by Lucanthone1. Cancer Invest. 2002;20(7–8):983–991.
  • Carew JS, Espitia CM, Esquivel JA, et al. Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. J Biol Chem. 2011;286(8):6602–6613.
  • Lopes A, Martins E, Silva R, et al. Chiral Thioxanthones as Modulators of P-glycoprotein: synthesis and Enantioselectivity Studies. Molecules. 2018;23(3):3.
  • Barbosa J, Lima R, Sousa D, et al. Screening a Small Library of Xanthones for Antitumor Activity and Identification of a Hit Compound which Induces Apoptosis. Molecules. 2016;21(1):81.
  • Lima RT, Sousa D, Paiva A, et al. Modulation of Autophagy by a Thioxanthone Decreases the Viability of Melanoma Cells. Molecules. 2016;21(10):10.
  • Chae SW, Woo S, Park JH, et al. Xanthone analogues as potent modulators of intestinal P-glycoprotein. Eur J Med Chem. 2015;93(p):237–245.
  • Rocha-Pereira C, Silva V, Costa VM, et al. Histological and toxicological evaluation, in rat, of a P-glycoprotein inducer and activator: 1-(propan-2-ylamino)-4-propoxy-9H-thioxanthen-9-one (TX5). Excli J. 2019;18(p):697–722.

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