Bioactive benzofuran derivatives: Moracins A-Z in medicinal chemistry

European Journal of Medicinal Chemistry

Volumn 90, Issue , 2015, Pages 379-393

  Naik, Ravi ^a   Harmalkar, Dipesh S ^a   Xu, Xuezhen ^a   Jang, Kyusic ^a   Lee, Kyeong ^a  

^a Dongguk University   (South Korea)

Author keywords

Benzofuran; Biological activity; Moracins; Mulberries

Indexed keywords

2 (3 HYDROXY 5 METHOXYPHENYL) 6 METHOXYBENZOFURAN 5 OL; 2 (3,5 DIHYDROXYPHENYL) 6 HYDROXYBENZOFURAN 5 CARBALDEHYDE; 2 (3,5 DIHYDROXYPHENYL) 7,7 DIMETHYL 6,7 DIHYDRO 5H FURO [3,2G] CHROMENE 5,6 DIOL; 2 (3,5 DIHYDROXYPHENYL) 8 METHYL 7,8 DIHYDROBENZOFURO [6,7B] OXEPINE 5,8 DIOL; 2 (3,5 DIMETHOXYPHENYL) 7,7 DIMETHYL 6,7 DIHYDRO 5H FURO [3,2G] CHROMEN 6 OL; 2 (5 HYDROXY 3 METHOXY 2 (3 METHYLBUT 2 ENYL) PHENYL) BENZOFURAN 6-OL; 3',5' DIHYDROXY FURAN (4",5":5,6) 2 ARYLBENZOFURAN; 5 (4 METHOXY 8 METHYL 7,10 DIHYDROBENZOFURO [6,7-B] OXEPIN 2 YL) BENZENE 1,3 DIOL; 5 (4,6 DIMETHOXYBENZOFURAN 2 YL) BENZENE 1,3 DIOL; 5 (5 (2,3 DIHYDROXY 3 METHYLBUTYL) 6 HYDROXYBENZOFURAN 2 YL) BENZENE 1,3 DIOL; 5 (5 HYDROXY 4 (7 HYDROXY 3,7 DIMETHYLOCT 2 ENYL) 7,7 DIMETHYL 7H FURO [3,2 FLCHROMEN 2 YL) BENZENE 1,3 DIOL; 5 (5 HYDROXY 6 METHOXYBENZOFURAN 2 YL) BENZENE 1,3 DIOL; 5 (5 HYDROXY 7,7 DIMETHYL 7H FURO [2,3F] CHROMEN 2 YL) BENZENE 1,3 DIOL; 5 (5 HYDROXY 8 METHYL 7,10 DIHYDROBENZOFURO [6,7B] OXEPIN 2 YL) BENZENE 1,3 DIOL; 5 (5,6 DIMETHOXYBENZOFURAN 2 YL)BENZENE 1,3 DIOL; 5 (6 HYDROXY 5 (3 METHYLBUT 2 ENYL) BENZOFURAN 2 YL) BENZENE 1,3 DIOL; 5 (6 HYDROXY 5 METHOXY 4 (3 METHYLBUT 2 ENYL) BENZOFURAN 2 YL) BENZENE 1,3 DIOL; 5 (6 HYDROXY 7,7 DIMETHYL 6,7 DIHYDRO 5H FURO [3,2G] CHROMEN 2 YL) BENZENE 1,3 DIOL; 5 (6 HYDROXYBENZOFURAN 2 YL) 2 (3 METHYLBUT 2 ENYL) BENZENE 1,3 DIOL; 5 (6 HYDROXYBENZOFURAN 2 YL) 2,2 DIMETHYL 2H CHROMEN 7 OL; 5 (6 HYDROXYBENZOFURAN 2 YL) BENZENE 1,3 DIOL; 5 (8 METHYL 7,10 DIHYDROBENZOFURO [6,7B] OXEPIN 2 YL) BENZENE 1,3 DIOL; 5 [6 (1 HYDROXY 1 METHYL ETHYL) 5,6 DIHYDRO BENZO [1,2B; 5,4B'] DIFURAN 2 YL] BENZENE 1,3 DIOL; 7 (6 HYDROXYBENZOFURAN 2 YL) 2,2 DIMETHYL 2H CHROMEN 5 OL; ANTIINFECTIVE AGENT; ANTIINFLAMMATORY AGENT; BENZOFURAN DERIVATIVE; MORACIN; PLANT EXTRACT; UNCLASSIFIED DRUG; UNINDEXED DRUG; ANTINEOPLASTIC AGENT; ANTIOXIDANT; BENZOFURAN; IMMUNOLOGIC FACTOR; NONSTEROID ANTIINFLAMMATORY AGENT;

ANTIDIABETIC ACTIVITY; ANTIINFLAMMATORY ACTIVITY; ANTIMICROBIAL ACTIVITY; ANTINEOPLASTIC ACTIVITY; ANTIOXIDANT ACTIVITY; BACTERIAL VIABILITY; BARK; CATALYST; CELL VIABILITY; COLUMN CHROMATOGRAPHY; CYCLIZATION; DEBENZYLATION; DIHYDROXYLATION; DRUG ACTIVITY; DRUG CYTOTOXICITY; DRUG ISOLATION; DRUG MECHANISM; DRUG SYNTHESIS; ENANTIOMER; ENZYME INHIBITION; EPOXIDATION; FATTY ACID SYNTHESIS; GRAM NEGATIVE BACTERIUM; GRAM POSITIVE BACTERIUM; HUMAN; IODINATION; MEDICINAL CHEMISTRY; MORUS; NONHUMAN; PLANT STEM; PROTEIN SYNTHESIS; REVIEW; SONOGASHIRA REACTION; ANIMAL; CHEMISTRY; ISOLATION AND PURIFICATION;

ANIMALS; ANTI-INFECTIVE AGENTS; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; ANTINEOPLASTIC AGENTS; ANTIOXIDANTS; BENZOFURANS; CHEMISTRY, PHARMACEUTICAL; HUMANS; IMMUNOLOGIC FACTORS;

EID: 84913582348     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2014.11.047     Document Type: Review

References (79)

1. L. Cordain, S.B. Eaton, A. Sebastian, N. Mann, S. Lindeberg, B.A. Watkins, et al., Origins and evolution of the western diet: health implications for the 21st century, Am. J. Clin. Nutr. 81 (2005) 341-354.
2. E. Fallon, L. Zhong, J.K. Furne, M.D. Levitt, A mixture of extracts of black and green teas and mulberry leaf did not reduce weight gain in rats fed a high fat diet, Altern. Med. Rev. 13 (2008) 43-49.
3. K.R. Venkatesh, C. Seema, Mulberry: life enhancer, J. Med. Plants Res. 2 (10) (2008) 271-278.
4. P.J. Fashing, Feeding ecology of Guerezas in the Kakamega Forest Kenya: the importance of Moraceae fruit in their diet, Int. J. Primatol. 22 (2001) 579-609.
5. V. Kuete, D.C. Fozing, W.F.G.D. Kapchec, A.T. Mbavengd, J.R. Kuiatea, B.T. Ngadjuib, B.M. Abegaze, Antimicrobial activity of the methanolic extract and compounds from Morus mesozygia stem bark, J. Ethnopharmacol. 124 (2009) 551-555.
6. G.D.W.F. Kapche, C.D. Fozing, J.H. Donfack, G.W. Fotso, D. Amadou, A.N. Tchana, M. Bezabih, P.F. Moundipa, B.T. Ngadjui, B.M. Abegaz, Prenylated arylbenzofuran derivatives from Morus mesozygia with antioxidant activity, Phytochemistry 70 (2009) 216-221.
7. T. Nomura, T. Fukai, M. Junko, A. Imashimizu, S. Terada, M. Hama, Constituents of the cultivated mulberry tree, Planta Med. 46 (1982) 167-174.
8. T. Nomura, T. Fukai, T. Hano, K. Nemoto, S. Terada, T. Kuramochi, Constituents of the cultivated mulberry tree, Planta Med. 47 (1983) 151-156.
9. Z. Chen, C. Zhu, Z. Han, Effects of aqueous chlorine dioxide treatment on nutritional components and shelf-life of mulberry fruit (Morus alba L.), J. Biosci. Bioeng. 111 (2011) 675-681.
10. L. Sang-Hee, C. Sang-Yoon, K. Hocheol, H. Jae-Sung, L. Byeong-Gon, G. Jian-Jun, K. Sun-Yeou, Mulberroside F isolated from the leaves of Morus alba inhibits melanin biosynthesis, Biol. Pharm. Bull. 25 (2002) 1045-1048.
11. T.D. Nguyen, X. Jin, K. Lee, Y.S. Hog, H.K. Young, J.L. Jung, Hypoxiainducible factor-1 inhibitory benzofurans and chalcone-derived DielseAlder adduct from Morus species, J. Nat. Prod. 72 (2009) 39-43.
12. W.S. Sheen, I.L. Tsai, C.M. Teng, I.S. Chen, Nor-neolignan and phenyl propanoid from Zanthoxylum ailanthoides, Phytochemistry 36 (1) (1994) 213-215.
13. H.M. Chang, K.P. Cheng, T.F. Choang, H.F. Chow, K.Y. Chui, P.M. Hon, F.W.L. Tan, Y. Yang, Z.P. Zhong, C.M. Lee, H.L. Sham, C.F. Chan, Y.X. Cui, H.N.C. Wong, Structure elucidation and total synthesis of new Tanshinones isolated from Salvia miltiorrhiza Bunge, J. Org. Chem. 55 (1990) 3537-3543.
14. I.L. Tsai, C.F. Hsieh, C.Y. Duh, Additional cytotoxic neolignans from Persea obovatifolia, Phytochemistry 48 (1998) 1371-1375.
15. Z.P. Zheng, K.W. Cheng, Q. Zhu, X.C. Wang, Z.X. Lin, M.F. Wang, Tyrosinase inhibitory constituents from the roots of Morus nigra: a structureeactivity relationship study, J. Agric. Food Chem. 58 (2010) 5368-5373.
16. H. Zelov-a, Z. Han-akov-a, Z.-Cerm-akov-a, K.-Smejkal, S.D. Acqua, P. Babula, J. Cva-cka, J. Ho-sek, Evaluation of anti-inflammatory activity of prenylated Substances isolated from Morus alba and Morus nigra, J. Nat. Prod. 77 (2014) 1297-1303.
17. W.M. Kone, K.K. Atindehou, C. Terrox, K. Hostettmann, D. Traore, M. Dosso, Traditional medicine in north Cote-d'Ivoire: screening of 50 medicinal plants for antibacterial activity, J. Ethnopharmacol. 93 (2004) 43-49.
18. Y.X. Tan, Y. Yang, T. Zhang, R.Y. Chen, D.-Q. Yu, Bioactive 2-arylbenzofuran derivatives from Morus wittiorum, Fitoterapia 81 (2010) 742-746.
19. T. Fukai, K. Kaitou, S. Terada, Antimicrobial activity of 2-arylbenzofurans from Morus species against methicillin-resistant Staphylococcus aureus, Fitoterapia 76 (2005) 708-711.
20. M. Royer, A.M.S. Rodrigues, G. Herbette, J. Beauchêne, M. Chevalier, B. H-erault, B. Thibaut, D. Stien, Efficacy of Bagassa guianensis Aubl. extract against wood decay and human pathogenic fungi, Int. Biodeterior. Biodegrad. 70 (2012) 55-59.
21. Y. Yamatake, M. Shibata, M. Nagai, Pharmacological studies on root bark of mulberry tree (Morus alba L.), Jpn. J. Pharmacol. 26 (1976) 461-469.
22. E.-S. Kim, S.-J. Park, E.-J. Lee, B.-K. Kim, H. Huh, B.-J. Lee, Purification and characterization of Moran 20K from Morus alba, Arch. Pharm. Res. 22 (1999) 9-12.
23. B. Andallu, V. Suryakantham, B.L. Srikanthi, G.K. Reddy, Effect of mulberry (Morus indica L.) therapy on plasma and erythrocyte membrane lipids in patients with type 2 diabetes, Clin. Chim. Acta. 314 (2001) 47-53.
24. H.M. Burkill, The Useful Plants of West Tropical Africa, vol. 4, Royal Botanic Gardens, Kew, 1985.
25. E. Noumi, T.W. Dibakto, Medicinal plants used for peptic ulcer in the Bangangte region, western Cameroon, Fitoterapia 71 (2002) 406-412.
26. S.G. Sun, R.Y. Chen, D.Q. Yu, Structures of two new benzofuran derivatives from the bark of mulberry tree (Morus macroura Miq.), J. Asian Nat. Prod. Res. 3 (2001) 253-259.
27. M. Takasugi, S. Nagao, T. Masamune, Structure of moracin A and B, new phytoalexins from diseased mulberry, Tetrahedron Lett. 19 (1978) 797-798.
28. Y.J. Kim, M.J. Sohn, W.G. Kim, Chalcomoracin and moracin C new inhibitors of Staphylococcus aureus enoyl-acyl carrier protein reductase from Morus alba, Biol. Pharm. Bull. 35 (2012) 791-795.
29. Y.M. Ferlinahayati, L.D. Syah, S.A. Juliawaty, E.H. Achmad, H. Hakim, I.M. Takayama, J.Z. Said, Latip, Phenolic constituents from the wood of Morus australis with cytotoxic activity, Naturforsch. C. J. Biosci. 63 (2008) 35-39.
30. M. Takasugi, S. Nagao, S. Ueno, T. Masamune, A. Shirata, K. Takahashi, Moracin C and D, new phytoalexins from diseased mulberry, Chem. Lett. 7 (1978) 1239-1240.
31. M. Takasugi, S. Nagao, T. Masamune, Structures of moracins e, F, g, and H, new phytoalexins from diseased mulberry, Tetrahedron Lett. 48 (1979) 4675-4678.
32. H.X. Yang, X. Hu, Isoprenylated phenolic compounds from leaves of Morus yunnanensis, Zhongguo Zhongyao Zazhi 38 (2013) 1735-1739.
33. L.-Q. Wang, Z.-R. Tang, W.-H. Mu, J.-F. Kou, D.-Y. He, A new natural naphtho [1,2-b]furan from the leaves of Cassia fistula, J. Asian Nat. Prod. Res. 15 (2013) 1210-1213.
34. Z.P. Zheng, Y. Xu, C. Qin, S. Zhang, X. Gu, Y. Lin, G. Xie, M. Wang, J. Chen, Characterization of antiproliferative activity constituents from Artocarpus heterophyllus, J. Agric. Food Chem. 62 (2014) 5519-5527.
35. C.D.A. Fozing, Z. Ali, B.T. Ngadjui, M.I. Choudhary, G.D.W.F. Kapche, B.M. Abegaz, I.A. Khan, Phosphodiesterase i-inhibiting DielseAlder adducts from the leaves of Morus mesozygia, Planta Med. 78 (2012) 154-159.
36. G.D.M. Kapche, P. Waffo-Teguo, S. Massip, J. Guillon, C. Vitrac, S. Krisa, B. Ngadjui, J.-M. Merillon, Crystal structure of Moracin M, Anal. Sci. X-Ray Struct. Anal. Online 23 (2007) 59-60.
37. Z. Yang, Y. Wang, Y. Wang, Y. Zhang, Bioassay-guided screening and isolation of a-glucosidase and tyrosinase inhibitors from leaves of Morus alba, Food Chem. 131 (2012) 617-625.
38. L. Cui, M.K. Na, H. Oh, E.Y. Bae, D.G. Jeong, S.E. Ryu, S. Kim, B.Y. Kim, W.K. Oha, J.S. Ahn, Protein tyrosine phosphatase 1B inhibitors from Morus root bark, Bioorg. Med. Chem. Lett. 16 (2006) 1426-1429.
39. Y. Yang, T. Gong, C. Liu, R.-Y. Cheen, Four new 2-arylbenzofuran derivatives from leaves of Morus alba L. Chem. Pharm. Bull. 58 (2010) 257-260.
40. M. Royer, G. Herbette, V. Eparvier, J. Beauchene, B. Thibaut, D. Stien, Secondary metabolites of Bagassa guianensis Aubl. wood: a study of the chemotaxonomy of the Moraceae family, Phytochemistry 71 (2010) 1708-1713.
41. T. Kinoshita, L. Ichinose, A short step convenient synthesis of 2-phenylbenzofuran form 3-phenylcoumarin, Heterocycles 65 (2005) 1641-1654.
42. S. Matsuyama, Y. Kuwahara, S. Nakamura, T. Suzuki, Oviposition stimulants for the lesser mulberry pyralid, Glyphodes pyloalis (Walker), in Mulberry leaves : rediscovery of phytoalexin componentsas insect kairomones, Agric. Biol. Chem. 55 (1991) 1333-1341.
43. I.S. Mann, D.A. Widdowson, J.M. Clough, Transition metal mediated synthesis of some prenylated phytoalexins of Morus alba Linn, Tetrahedron 47 (1991) 7991-8000.
44. G.D. McAllister, R.C. Hartley, M.J. Dawson, A.R. Knaggs, Total synthesis of Moracin C, J. Chem. Soc. Perkin Trans. 1 (1998) 3453-3458.
45. L. Arias, Y. Vara, F.P. Cossío, Regioselective preparation of benzo[b]furans from phenols and a-bromoketones, J. Org. Chem. 77 (2012) 266-275.
46. J.M. Clough, I.S. Mann, D.A. Widdowson, Transition metal mediated organic synthesis: the synthesis of moracin M, Tetrahedron Lett. 28 (1987) 2645-2648.
47. J.A. Celaje, D. Zhang, A.M. Guerrero, M. Selke, Chemistry of trans-resveratrol with singlet oxygen: [2+2] addition, [4+2] addition, and formation of the phytoalexin moracin m, Org. Lett. 13 (2011) 4846-4849.
48. N. Kaur, Y. Xia, Y. Jin, N.T. Dat, K. Gajulapati, Y. Choi, Y.-S. Hong, J.J. Lee, K. Lee, The first total synthesis of Moracin O and Moracin P, and establishment of the absolute configuration of Moracin O, Chem. Commun. 14 (2009) 1879-1881.
49. Y. Xia, Y. Jin, N. Kaur, Y. Choi, K. Lee, HIF-1a inhibitors: synthesis and biological evaluation of novel Moracin O and P analogues, Eur. J. Med. Chem. 46 (2011) 2386-2396.
50. H. Adcock, Pharmageddon: is it too late to tackle growing resistance to antiinfectives? Pharm. J. 269 (2002) 599-600.
51. S. Reinberg, Health Day News, World Health Organization, 2008.
52. K.A. Mohammed, R.C. Jadulco, T.S. Bugni, M.K. Harper, M. Sturdy, C.M. Ireland, Strongylophorines: natural product inhibitors of hypoxia-inducible factor-1 transcriptional pathway, J. Med. Chem. 51 (2008) 1402-1405.
53. A.L. Harris, Hypoxia e a key regulatory factor in tumour growth, Nat. Rev. 2 (2002) 38-47.
54. K. Lee, J.H. Lee, S.K. Boovanahalli, Y. Jin, M. Lee, X. Jin, J.H. Kim, Y.S. Hong, J.J. Lee, (Aryloxyacetylamino)benzoic acid analogues: a new class of hypoxiainducible factor-1 inhibitors, J. Med. Chem. 50 (2007) 1675-1684.
55. S.K. Boovanahalli, X. Jin, Y. Jin, J.H. Kim, N.T. Dat, Y.S. Hong, J.H. Lee, S.H. Jung, K. Lee, J.J. Lee, Synthesis of (aryloxyacetylamino)-isonicotinic/nicotinic acid analogues as potent hypoxia-inducible factor (HIF)-1alpha inhibitors, Bioorg. Med. Chem. Lett. 17 (2007) 6305-6310.
56. C.L. Vogel, Hormonal approaches to breast cancer treatment and prevention: an overview, Semin. Oncol. 23 (1996) 2-9.
57. D. Henderson, U.-F. Habenicht, Y. Nishino, M.F. el Etreby, Estrogens and benign prostatic hyperplasia: the basis for aromatase inhibitor therapy, Steroids 50 (1987) 219-233.
58. G.J. Kelloff, R.A. Lubet, R. Lieberman, K. Eisenhauer, V.E. Steele, J.A. Crowell, E.T. Hawk, C.W. Boone, C.C. Sigman, Aromatase inhibitors as potential cancer chemopreventives, Cancer Epidemiol. Biomark. Prev. 7 (1998) 65-78.
59. D. Lee, K.P.L. Bhat, H.H.S. Fong, N.R. Farnsworth, J.M. Pezzuto, A.D. Kinghorn, Aromatase inhibitors from Broussonetia papyrifera, J. Nat. Prod. 64 (2001) 1286-1293.
60. I. Gulcin, Antioxidant activity of L-adrenaline: an activity-structure insight, Chem. Biol. Interact. 179 (2009) 71-80.
61. B. Halliwell, R. Aeshbach, J. Loliger, O.I. Aruoma, The characterization of antioxidants, Food Chem. Toxicol. 33 (1995) 601-617.
62. B. Halliwell, J.M.C. Gutteridge, Free Radicals in Biology and Medicine, Clarendon Press, Oxford, 1989, p. 331.
63. W. BrandWilliams, M.E. Cuvelier, C. Berset, Use of free radical method to evaluate antioxidant activity, Leb. Wiss Technol. 28 (1995) 25-30.
64. R. Sharma, A. Sharma, T. Shono, M. Takasugi, A. Shirata, T. Fujimura, H. Machii, Mulberry Moracins: scavengers of UV stress-generated free radicals, Biosci. Biotechnol. Biochem. 65 (2001) 1402-1405.
65. H.W. Ryu, B.W. Lee, M.J. Curtis-Long, S. Jung, Y.B. Ryu, W.S. Lee, Polyphenols from Broussonetia papyrifera displaying potent a-glucosidase inhibition, J. Agric. Food Chem. 58 (2009) 202-208.
66. P. Han, C.Q. Chen, C.L. Zhang, K.K. Song, H.T. Zhou, Q.X. Chen, Inhibitory effects of 4-chlorosalicylic acid on mushroom tyrosinase and its antimicrobial activities, Food Chem. 107 (2008) 797-803.
67. X. Hu, M. Wang, G. Rui Yan, M.-H. Yu, H.-Y. Wang, A.-J. Hou, 2-Arylbenzofuran and tyrosinase inhibitory constituents of Morus notabilis, J. Asian Nat. Prod. Res. 14 (12) (2012) 1103-1108.
68. C.L. Yen, S.J. Stone, S. Koliwad, C. Harris, R.V. Farese Jr., Thematic review series: glycerolipids. DGAT enzymes and triacylglycerol biosynthesis, J. Lipid Res. 49 (2008) 2283-2301.
69. Z.-G. Yang, K. Matsuzaki, S. Takamatsu, S. Kitanaka, Inhibitory effects of constituents from Morus alba var. multicaulis on differentiation of 3T3-L1 cells and nitric oxide production in RAW264.7 cells, Molecules 16 (2011) 6010-6022.
70. D.J. Wolff, D.S. Gauld, M.J. Neulander, G. Southan, Inactivation of nitric oxide synthase by substituted aminoguanidines and aminoisothioureas, J. Pharmacol. Exp. Ther. 283 (1997) 265-273.
71. M. Zhang, M. Chen, H.-Q. Zhang, S. Sun, B. Xia, F.-H. Wu, In vivo hypoglycemic effects of phenolics from the root bark of Morus alba, Fitoterapia 80 (2009) 475-477.
72. M. Conti, J. Beavo, Biochemistry and physiology of cyclic nucleotide phosphodiesterases: essential components in cyclic nucleotide signaling, Annu. Rev. Biochem. 76 (2007) 481-511.
73. H. Ke, H. Wang, Crystal structures of phosphodiesterases and implications on substrate specificity and inhibitor selectivity, Curr. Top. Med. Chem. 7 (2007) 391-403.
74. S.-K. Chen, P. Zhao, Y.-X. Shao, Z. Li, C. Zhang, P. Liu, X. He, H.-B. Luo, X. Hu, Moracin M from Morus alba L. is a natural phosphodiesterase-4 inhibitor, Bioorg. Med. Chem. Lett. 22 (2012) 3261-3264.
75. R. Medzhitov, Inflammation 2010: new adventures of an old flame, Cell (2010) 771-776.
76. S. Grivennikov, F.R. Greten, M. Karin, Immunity, inflammation, and cancer, Cell 140 (2010) 883-899.
77. C. Nathan, Points of control in inflammation, Nature 420 (2002) 846-852.
78. B.N. Cronstein, G. Weissmann, Targets for antiinflammatory drugs, Annu. Rev. Pharmacol. Toxicol. 35 (1995) 449-462.
79. C.A. Feghali, T.M. Wright, Cytokines in acute and chronic inflammation, Front. Biosci. 2 (1997) 12-26.