Polyisoprenylated benzophenones from clusiaceae: Potential drugs and lead compounds

Current Topics in Medicinal Chemistry

Volumn 9, Issue 16, 2009, Pages 1560-1580

  Acuña, Ulyana Muñoz ^a,b   Jancovski, Nikola ^a   Kennelly, Edward J ^a,b  

^a CITY UNIVERSITY OF NEW YORK   (United States)

^b CITY UNIVERSITY OF NEW YORK   (United States)

Author keywords

Antimicrobial; Apoptosis; Benzophenones; Clusiaceae; Cytotoxicity; Garcinol; Polyisoprenylated

Indexed keywords

ACTIVATING TRANSCRIPTION FACTOR 4; ARISTOPHENONE A; BENZOPHENONE DERIVATIVE; BICYCLO[3.3.1]NONANE 2,4,9 TRIONE; CUDRAPHENONE A; CUDRAPHENONE B; CUDRAPHENONE C; CUDRAPHENONE D; GARCINOL; GROWTH ARREST AND DNA DAMAGE INDUCIBLE PROTEIN 153; GUTTIFERONE A; GUTTIFERONE E; GUTTIFERONE G; GUTTIFERONE H; GUTTIFERONE I; GUTTIFERONE J; GUTTIFERONE K; GUTTIFERONE L; GW 678248; HYPERIBONE K; HYPERIBONE L; ISOGARCINOL; ISOXANTHOCHYMOL; NEMOROSONE; OCHROCARPINONE A; OCHROCARPINONE B; RNA DIRECTED DNA POLYMERASE INHIBITOR; TOVOPHENONE A; UNCLASSIFIED DRUG; UNINDEXED DRUG; X BOX BINDING PROTEIN 1;

ANTIINFLAMMATORY ACTIVITY; ANTIOXIDANT ACTIVITY; COLON CANCER; DOWN REGULATION; DRUG ABSORPTION; DRUG CYTOTOXICITY; DRUG ISOLATION; DRUG METABOLISM; DRUG SYNTHESIS; GENE EXPRESSION REGULATION; GUTTIFERAE; HUMAN; INFLAMMATION; ISOPRENYLATION; METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS; NONHUMAN; ONCOGENE C MYB; OXIDATIVE STRESS; REVIEW; STRUCTURE ACTIVITY RELATION;

ANIMALS; ANTI-INFECTIVE AGENTS; ANTINEOPLASTIC AGENTS, PHYTOGENIC; BENZOPHENONES; CLUSIACEAE; DRUG EVALUATION, PRECLINICAL; HUMANS;

EID: 74249105372     PISSN: 15680266     EISSN: None     Source Type: Journal    
DOI: 10.2174/156802609789909830     Document Type: Review

References (72)

1. Newman, D. J.; Cragg, G. M. Natural products as sources of new drugs over the last 25 years. J. Nat. Prod. 2007, 70, 461-477.
2. Gulick, R. M.; McAuliffe, V.; Holden-Wiltse, J.; Crumpacker, C.; Liebes, L.; Stein, D. S.; Meehan, P.; Hussey, S.; Forcht, J.; Valentine, F. T. Phase I studies of hypericin, the active compound in St. John's Wort, as an antiretroviral agent in HIV-infected adults. AIDS Clinical Trials Group Protocols 150 and 258. Ann. Intern. Med. 1999, 130, 510-514.
3. Beerhues, L. Benzophenone synthase from cultured cells of Centaurium erythraea. FEBS Lett. 1996, 383, 264-266.
4. McCandlish, L. E.; Hanson, J. C.; Stout, G. H. The structures of two derivatives of bicyclo[3.3.1]nonane-2,4,9-trione. A natural product: clusianone, C33H42O4, and trimethylated catechinic acid, C18H20O6. Acta Crystallogr. Sect. B 1976, B32, 1793-1801.
5. Kumar, S.; Chattopadhyay, S. K.; Darokar, M. P.; Garg, A.; Khanuja, S. P. Cytotoxic activities of xanthochymol and isoxanthochymol substantiated by LC-MS/MS. Planta Med. 2007, 73, 1452-1456.
6. Kuete, V.; Komguem, J.; Beng, V. P.; Meli, A. L.; Tangmouo, J. G.; Etoa, F. X.; Lontsi, D. Antimicrobial components of the methanolic extract from the stem bark of Garcinia smeathmannii Oliver (Clusiaceae). S. Afr. J. Bot. 2007, 73, 347-354.
7. Xiao, Z. Y.; Mu, Q.; Shiu, W. K.; Zeng, Y. H.; Gibbons, S. Polyisoprenylated benzoylphloroglucinol derivatives from Hypericum sampsonii. J. Nat. Prod. 2007, 70, 1779-1782.
8. Fuller, R. W.; Blunt, J. W.; Boswell, J. L.; Cardellina, J. H., 2nd; Boyd, M. R. Guttiferone F, the first prenylated benzophenone from Allanblackia stuhlmannii. J. Nat. Prod. 1999, 62, 130-132.
9. Liao, C. H.; Ho, C. T.; Lin, J. K. Effects of garcinol on free radical generation and NO production in embryonic rat cortical neurons and astrocytes. Biochem. Biophys. Res. Commun. 2005, 329, 1306-1314.
10. Baggett, S.; Protiva, P.; Mazzola, E. P.; Yang, H.; Ressler, E. T.; Basile, M. J.; Weinstein, I. B.; Kennelly, E. J. Bioactive benzophenones from Garcinia xanthochymus fruits. J. Nat. Prod. 2005, 68, 354-360.
11. Yamaguchi, F.; Saito, M.; Ariga, T.; Yoshimura, Y.; Nakazawa, H. Free radical scavenging activity and antiulcer activity of garcinol from Garcinia indica fruit rind. J. Agric. Food Chem. 2000, 48, 2320-2325.
12. Hong, J.; Kwon, S. J.; Sang, S.; Ju, J.; Zhou, J. N.; Ho, C. T.; Huang, M. T.; Yang, C. S. Effects of garcinol and its derivatives on intestinal cell growth: Inhibitory effects and autoxidation-dependent growth-stimulatory effects. Free Radic. Biol. Med. 2007, 42, 1211-1221.
13. Wu, C. C.; Weng, J. R.; Won, S. J.; Lin, C. N. Constituents of the pericarp of Garcinia subelliptica. J. Nat. Prod. 2005, 68, 1125-1127.
14. Pecchio, M.; Solis, P. N.; Lopez-Perez, J. L.; Vasquez, Y.; Rodriguez, N.; Olmedo, D.; Correa, M.; San Feliciano, A.; Gupta, M. P. Cytotoxic and antimicrobial benzophenones from the leaves of Tovomita longifolia. J. Nat. Prod. 2006, 69, 410-413.
15. Tanaka, N.; Takaishi, Y.; Shikishima, Y.; Nakanishi, Y.; Bastow, K.; Lee, K. H.; Honda, G.; Ito, M.; Takeda, Y.; Kodzhimatov, O. K.; Ashurmetov, O. Prenylated benzophenones and xanthones from Hypericum scabrum. J. Nat. Prod. 2004, 67, 1870-1875.
16. Chaturvedula, V. S.; Schilling, J. K.; Kingston, D. G. New cytotoxic coumarins and prenylated benzophenone derivatives from the bark of Ochrocarpos punctatus from the Madagascar rainforest. J. Nat. Prod. 2002, 65, 965-972.
17. Cao, S.; Brodie, P. J.; Miller, J. S.; Ratovoson, F.; Birkinshaw, C.; Randrianasolo, S.; Rakotobe, E.; Rasamison, V. E.; Kingston, D. G. I. Guttiferones K and L, Antiproliferative compounds of Rheedia calcicola from the Madagascar rain forest. J. Nat. Prod. 2007, 70, 686-688.
18. Williams, R. B.; Hoch, J.; Glass, T. E.; Evans, R.; Miller, J. S.; Wisse, J. H.; Kingston, D. G. A novel cytotoxic guttiferone analogue from Garcinia macrophylla from the Suriname rainforest. Planta Med. 2003, 69, 864-866.
19. Roux, D.; Hadi, H. A.; Thoret, S.; Guenard, D.; Thoison, O.; Paies, M.; Sevenet, T. Structure-activity relationship of polyisoprenyl benzophenones from Garcinia pyrifera on the tubulin/microtubule system. J. Nat. Prod. 2000, 63, 1070-1076.
20. Seo, E. K.; Wani, M. C.; Wall, M. E.; Navarro, H.; Mukherjee, R.; Farnsworth, N. R.; Kinghorn, A. D. New bioactive aromatic compounds from Vismia guianensis. Phytochemistry 2000, 55, 35-42.
21. Diaz-Carballo, D.; Malak, S.; Freistuhler, M.; Elmaagacli, A.; Bardenheuer, W.; Reusch, H. P. Nemorosone blocks proliferation and induces apoptosis in leukemia cells. Int. J. Clin. Pharmacol. Ther. 2008, 46, 428-439.
22. Matsumoto, K.; Akao, Y.; Kobayashi, E.; Ito, T.; Ohguchi, K.; Tanaka, T.; Iinuma, M.; Nozawa, Y. Cytotoxic benzophenone derivatives from Garcinia species display a strong apoptosis-inducing effect against human leukemia cell lines. Biol. Pharm. Bull. 2003, 26, 569-571.
23. Protiva, P.; Hopkins, M. E.; Baggett, S.; Yang, H.; Lipkin, M.; Holt, P. R.; Kennelly, E. J.; Bernard, W. I. Growth inhibition of colon cancer cells by polyisoprenylated benzophenones is associated with induction of the endoplasmic reticulum response. Int. J. Cancer 2008, 123, 687-694.
24. Balasubramanyam, K.; Altaf, M.; Varier, R. A.; Swaminathan, V.; Ravindran, A.; Sadhale, P. P.; Kundu, T. K. Polyisoprenylated benzophenone, garcinol, a natural histone acetyltransferase inhibitor, represses chromatin transcription and alters global gene expression. J. Biol. Chem. 2004, 279, 33716-33726.
25. Martins, F. T.; Assis, D. M.; Dos Santos, M. H.; Camps, I.; Veloso, M. P.; Juliano, M. A.; Alves, L. C.; Doriguetto, A. C. Natural polyprenylated benzophenones inhibiting cysteine and serine proteases. Eur. J. Med. Chem. 2008, 44, 1-10.
26. Wu, C. C.; Lu, Y. H.; Wei, B. L.; Yang, S. C.; Won, S. J.; Lin, C. N. Phloroglucinols with prooxidant activity from Garcinia subelliptica. J. Nat. Prod. 2008, 71, 246-250.
27. Hong, J.; Kwon Seok, J.; Sang, S.; Ju, J.; Zhou, J.-N.; Ho, C.-T.; Huang, M.-T.; Yang Chung, S. Effects of garcinol and its derivatives on intestinal cell growth: Inhibitory effects and autoxidation-dependent growth-stimulatory effects. Free Radic. Biol. Med. 2007, 42, 1211-1221.
28. Pan, M. H.; Chang, W. L.; Lin-Shiau, S. Y.; Ho, C. T.; Lin, J. K. Induction of apoptosis by garcinol and curcumin through cytochrome c release and activation of caspases in human leukemia HL-60 cells. J. Agric. Food Chem. 2001, 49, 1464-1474.
29. Marquez Hernandez, I.; Campo Fernandez, M.; Cuesta-Rubio, O.; Piccinelli, A. L.; Rastrelli, L. Polyprenylated benzophenone derivatives from Cuban propolis. J. Nat. Prod. 2005, 68, 931-934.
30. Hou, A.; Fukai, T.; Shimazaki, M.; Sakagami, H.; Sun, H.; Nomura, T. Benzophenones and xanthones with isoprenoid groups from Cudrania cochinchinensis. J. Nat. Prod. 2001, 64, 65-70.
31. Li, E.; Jiang, L.; Guo, L.; Zhang, H.; Che, Y. Pestalachlorides A-C, antifungal metabolites from the plant endophytic fungus Pestalotiopsis adusta. Bioorg. Med. Chem. 2008, 16, 7894-7899.
32. Merza, J.; Mallet, S.; Litaudon, M.; Dumontet, V.; Seraphin, D.; Richomme, P. New cytotoxic guttiferone analogues from Garcinia virgata from New Caledonia. Planta Med. 2006, 72, 87-89.
33. Kumar, S.; Chattopadhyay, S. K. High-performance liquid chromatography and LC-ESI-MS method for the identification and quantification of two biologically active polyisoprenylated benzophenones xanthochymol and isoxanthochymol in different parts of Garcinia indica. Biomed. Chromatogr. 2007, 21, 139-163.
34. Xu, G.; Feng, C.; Zhou, Y.; Han, Q. B.; Qiao, C. F.; Huang, S. X.; Chang, D. C.; Zhao, Q. S.; Luo, K. Q.; Xu, H. X. Bioassay and ultraperformance liquid chromatography/mass spectrometry guided isolation of apoptosis-inducing benzophenones and xanthone from the pericarp of Garcinia yunnanensis Hu. J. Agric. Food Chem. 2008, 56, 11144-11150.
35. Seo, E. K.; Wall, M. E.; Wani, M. C.; Navarro, H.; Mukherjee, R.; Farnsworth, N. R.; Kinghorn, A. D. Cytotoxic constituents from the roots of Tovomita brevistaminea. Phytochemistry 1999, 52, 669-674.
36. Krishnamurthy, N.; Lewis, Y. S.; Ravindranath, B. On the structure of garcinol, isogarcinol, and camboginol. Tetrahedron Lett. 1981, 22, 793-796.
37. Ito, C.; Itoigawa, M.; Miyamoto, Y.; Onoda, S.; Rao, K. S.; Mukainaka, T.; Tokuda, H.; Nishino, H.; Furukawa, H. Polyprenylated benzophenones from Garcinia assigu and their potential cancer chemopreventive activities. J. Nat. Prod. 2003, 66, 206-209.
38. Sang, S.; Pan, M.-H.; Cheng, X.; Bai, N.; Stark, R. E.; Rosen, R. T.; Lin-Shiau, S.-Y.; Lin, J.-K.; Ho, C.-T. Chemical studies on antioxidant mechanism of garcinol: analysis of radical reaction products of garcinol and their antitumor activities. Tetrahedron 2001, 57, 9931-9938.
39. Yu, S.; Shen, G.; Khor, T. O.; Kim, J. H.; Kong, A. N. Curcumin inhibits Akt/mammalian target of rapamycin signaling through protein phosphatase- dependent mechanism. Mol. Cancer Ther. 2008, 7, 2609-2620.
40. Lin, H. Y.; Chen, C. S.; Lin, S. P.; Weng, J. R. Targeting histone deacetylase in cancer therapy. Med. Res. Rev. 2006, 26, 397-413.
41. Martins, F. T.; Cruz, J. W., Jr.; Derogis, P. B. M. C.; dos Santos, M. H.; Veloso, M. P.; Ellena, J.; Doriguetto, A. C. Natural polyprenylated benzophenones: keto-enol tautomerism and stereochemistry. J. Braz. Chem. Soc. 2007, 18, 1515-1523.
42. Kumazawa, E.; Hirotani, K.; Burford, S. C.; Kawagoe, K.; Miwa, T.; Mitsui, I.; Ejima, A. Synthesis and antitumor activity of novel benzophenone derivatives. Chem. Pharm. Bull. 1997, 45, 1470-1474.
43. Tanaka, T.; Kohno, H.; Shimada, R.; Kagami, S.; Yamaguchi, F.; Kataoka, S.; Ariga, T.; Murakami, A.; Koshimizu, K.; Ohigashi, H. Prevention of colonic aberrant crypt foci by dietary feeding of garcinol in male F344 rats. Carcinogenesis 2000, 21, 1183-1189.
44. Iinuma, M.; Tosa, H.; Tanaka, T.; Asai, F.; Kobayashi, Y.; Shimano, R.; Miyauchi, K. Antibacterial activity of xanthones from guttiferaeous plants against methicillin-resistant Staphylococcus aureus. J. Pharm. Pharmacol. 1996, 48, 861-865.
45. Rukachaisirikul, V.; Naklue, W.; Sukpondma, Y.; Phongpaichit, S. An antibacterial biphenyl derivative from Garcinia bancana MIQ. Chem. Pharm. Bull. 2005, 53, 342-343.
46. Almeida, L. S.; Murata, R. M.; Yatsuda, R.; Dos Santos, M. H.; Nagem, T. J.; Alencar, S. M.; Koo, H.; Rosalen, P. L. Antimicrobial activity of Rheedia brasiliensis and 7-epiclusianone against Streptococcus mutans. Phytomedicine 2008, 15, 886-891.
47. Negi, P. S.; Jayaprakasha, G. K.; Jena, B. S. Antibacterial activity of the extracts from the fruit rinds of Garcinia cowa and Garcinia pedunculata against food borne pathogens and spoilage bacteria. Food Sci. Tech. 2008, 41, 1857-1861.
48. Lokvam, J.; Braddock, J. F.; Reichardt, P. B.; Clausen, T. P. Two polyisoprenylated benzophenones from the trunk latex of Clusia grandiflora (Clusiaceae). Phytochemistry 2000, 55, 29-34.
49. Cuesta-Rubio, O.; Padron, A.; Castro, H. V.; Pizza, C.; Rastrelli, L. Aristophenones A and B. A new tautomeric pair of polyisoprenylated benzophenones from Garcinia aristata. J. Nat. Prod. 2001, 64, 973-975.
50. Cuesta-Rubio, O.; Frontana-Uribe, B. A.; Ramirez-Apan, T.; Cardenas, J. Polyisoprenylated benzophenones in Cuban propolis; biological activity of nemorosone. Z. Naturforsch., C: J. Biosci. 2002, 57, 372-378.
51. Cueto, M.; Jensen, P. R.; Kauffman, C.; Fenical, W.; Lobkovsky, E.; Clardy, J. Pestalone, a new antibiotic produced by a marine fungus in response to bacterial challenge. J. Nat. Prod. 2001, 64, 1444-1446.
52. Yoganathan, K.; Cao, S.; Crasta, S. C.; Aitipamula, S.; Whitton, S. R.; Ng, S.; Buss, A. D.; Butler, M. S. Microsphaerins A-D, four novel benzophenone dimers with activity against MRSA from the fungus Microsphaeropsis sp. Tetrahedron 2008, 64, 10181-10187.
53. Gustafson, K. R.; Blunt, J. W.; Munro, M. H. G.; Fuller, R. W.; McKee, T. C.; Cardellina, J. H., 2nd; McMahon, J. B.; Cragg, G. M.; Boyd, M. R. HIV inhibitory natural products. 8. The guttiferones, HIV-inhibitory benzophenones from Symphonia globulifera, Garcinia livingstonei, Garcinia ovalifolia and Clusia rosea. Tetrahedron 1992, 48, 10093-10102.
54. Rukachaisirikul, V.; Pailee, P.; Hiranrat, A.; Tuchinda, P.; Yoosook, C.; Kasisit, J.; Taylor, W. C.; Reutrakul, V. Anti-HIV-1 protostane triterpenes and digeranylbenzophenone from trunk bark and stems of Garcinia speciosa. Planta Med. 2003, 69, 1141-1146.
55. Fuller, R. W.; Westergaard, C. K.; Collins, J. W.; Cardellina, J. H., 2nd; Boyd, M. R. Vismiaphenones D-G, new prenylated benzophenones from Vismia cayennensis. J. Nat. Prod. 1999, 62, 67-69.
56. Ferris, R. G.; Hazen, R. J.; Roberts, G. B.; St Clair, M. H.; Chan, J. H.; Romines, K. R.; Freeman, G. A.; Tidwell, J. H.; Schaller, L. T.; Cowan, J. R.; Short, S. A.; Weaver, K. L.; Selleseth, D. W.; Moniri, K. R.; Boone, L. R. Antiviral activity of GW678248, a novel benzophenone nonnucleoside reverse transcriptase inhibitor. Antimicrob. Agents Chemother. 2005, 49, 4046-4051.
57. Romines, K. R.; Freeman, G. A.; Schaller, L. T.; Cowan, J. R.; Gonzales, S. S.; Tidwell, J. H.; Andrews, C. W., 3rd; Stammers, D. K.; Hazen, R. J.; Ferris, R. G.; Short, S. A.; Chan, J. H.; Boone, L. R. Structure-activity relationship studies of novel benzophenones leading to the discovery of a potent, next generation HIV non-nucleoside reverse transcriptase inhibitor. J. Med. Chem. 2006, 49, 727-739.
58. Chan, J. H.; Freeman, G. A.; Tidwell, J. H.; Romines, K. R.; Schaller, L. T.; Cowan, J. R.; Gonzales, S. S.; Lowell, G. S.; Andrews, C. W., 3rd; Reynolds, D. J.; St Clair, M.; Hazen, R. J.; Ferris, R. G.; Creech, K. L.; Roberts, G. B.; Short, S. A.; Weaver, K.; Koszalka, G. W.; Boone, L. R. Novel benzophenones as non-nucleoside reverse transcriptase inhibitors of HIV-1. J. Med. Chem. 2004, 47, 1175-1182.
59. Abe, F.; Nagafuji, S.; Okabe, H.; Akahane, H.; Estrada-Muniz, E.; Huerta-Reyes, M.; Reyes-Chilpa, R. Trypanocidal constituents in plants 3. Leaves of Garcinia intermedia and heartwood of Calophyllum brasiliense. Biol. Pharm. Bull. 2004, 27, 141-143.
60. Lenta, B. N.; Vonthron-Senecheau, C.; Weniger, B.; Devkota, K. P.; Ngoupayo, J.; Kaiser, M.; Naz, Q.; Choudhary, M. I.; Tsamo, E.; Sewald, N. Leishmanicidal and cholinesterase inhibiting activities of phenolic compounds from Allanblackia monticola and Symphonia globulifera. Molecules 2007, 12, 1548-1557.
61. Alves, T. M.; Alves, R.; Romanha, A. J.; Zani, C. L.; dos Santos, M. H.; Nagem, T. J. Biological activities of 7-epiclusianone. J. Nat. Prod. 1999, 62, 369-371.
62. Marti, G.; Eparvier, V.; Moretti, C.; Susplugas, S.; Prado, S.; Grellier, P.; Retailleau, P.; Gueritte, F.; Litaudon, M. Antiplasmodial benzophenones from the trunk latex of Moronobea coccinea (Clusiaceae). Phytochemistry 2008.
63. Ngouela, S.; Lenta, B. N.; Noungoue, D. T.; Ngoupayo, J.; Boyom, F. F.; Tsamo, E.; Gut, J.; Rosenthal, P. J.; Connolly, J. D. Antiplasmodial and antioxidant activities of constituents of the seed shells of Symphonia globulifera Linn f. Phytochemistry 2006, 67, 302-306.
64. Yamaguchi, F.; Ariga, T.; Yoshimura, Y.; Nakazawa, H. Antioxidative and anti-glycation activity of garcinol from Garcinia indica fruit rind. J. Agric. Food Chem. 2000, 48, 180-185.
65. Neves, J. S.; Coelho, L. P.; Cordeiro, R. S.; Veloso, M. P.; Rodrigues e Silva, P. M.; dos Santos, M. H.; Martins, M. A. Antianaphylactic properties of 7-epiclusianone, a tetraprenylated benzophenone isolated from Garcinia brasiliensis. Planta Med. 2007, 73, 644-649.
66. Hong, J.; Sang, S.; Park, H.-J.; Kwon Seok, J.; Suh, N.; Huang, M.-T.; Ho, C.-T.; Yang Chung, S. Modulation of arachidonic acid metabolism and nitric oxide synthesis by garcinol and its derivatives. Carcinogenesis 2006, 27, 278-286.
67. Koeberle, A.; Northoff, H.; Werz, O. Identification of 5-lipoxygenase and microsomal prostaglandin E2 synthase-1 as functional targets of the anti-inflammatory and anti-carcinogenic garcinol. Biochem. Pharmacol. 2009, 77, 1513-1521.
68. Demirkiran, O.; Ahmed Mesaik, M.; Beynek, H.; Abbaskhan, A.; Iqbal Choudhary, M. Cellular reactive oxygen species, inhibitory constituents of Hypericum thasium Griseb. Phytochemistry 2009, 70, 244-249.
69. Seidlova-Wuttke, D.; Jarry, H.; Wuttke, W. Pure estrogenic effect of benzophenone-2 (BP2) but not of bisphenol A (BPA) and dibutylphtalate (DBP) in uterus, vagina and bone. Toxicology 2004, 205, 103-112.
70. Schlecht, C.; Klammer, H.; Frauendorf, H.; Wuttke, W.; Jarry, H. Pharmacokinetics and metabolism of benzophenone 2 in the rat. Toxicology 2008, 245, 11-17.
71. Jeon, H. K.; Sarma, S. N.; Kim, Y. J.; Ryu, J. C. Toxicokinetics and metabolisms of benzophenone-type UV filters in rats. Toxicology 2008, 248, 89-95.
72. Mitcheva, M.; Kondeva, M.; Vitcheva, V.; Nedialkov, P.; Kitanov, G. Effect of benzophenones from Hypericum annulatum on carbon tetrachloride-induced toxicity in freshly isolated rat hepatocytes. Redox. Rep. 2006, 11, 3-8.