Novel locally active estrogens accelerate cutaneous wound healing. A preliminary study

Molecular Pharmaceutics

Volumn 6, Issue 2, 2009, Pages 543-556

  Brufani, Mario ^a   Ceccacci, Francesca ^a   Filocamo, Luigi ^a   Garofalo, Barbara ^a   Joudioux, Roberta ^a   Bella, Angela La ^a   Leonelli, Francesca ^a   Migneco, Luisa M ^a   Bettolo, Rinaldo Marini ^a   Farina, Paolo M ^b   Ashcroft, Gillian S ^c   Routley, Claire ^c   Hardman, Matthew ^c   Meda, Clara ^d   Rando, Gianpaolo ^d   Maggi, Adriana ^a,d  

^a SAPIENZA UNIVERSITY OF ROME   (Italy)

^b Euticals Ambrosia SpA   (Italy)

^c UNIVERSITY OF MANCHESTER   (United Kingdom)

^d UNIVERSITY OF MILAN   (Italy)

Author keywords

Estrogen receptor; Locally active estrogens; Soft drugs; Wound healing

Indexed keywords

3,17 BETA HYDROXY 17 ALPHA (5' ACETOXY 1' PENTYN 1' YL)ESTRA 1,3,5(10) TRIENE; ESTRADIOL DERIVATIVE; ESTROGEN RECEPTOR; ESTRONE DERIVATIVE; INTERLEUKIN 6; ORGANOMETALLIC COMPOUND; TRANSFORMING GROWTH FACTOR BETA1; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BINDING AFFINITY; BINDING COMPETITION; CONTROLLED STUDY; DRUG RECEPTOR BINDING; DRUG STRUCTURE; DRUG SYNTHESIS; ESTROGEN ACTIVITY; FEMALE; HUMAN; HUMAN CELL; IMMUNOHISTOCHEMISTRY; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; REAL TIME POLYMERASE CHAIN REACTION; TRANSACTIVATION; WOUND HEALING;

ANIMALS; BREAST NEOPLASMS; ESTRADIOL; ESTROGENS; FEMALE; HUMANS; MICE; MICE, INBRED C57BL; OVARIECTOMY; RECEPTORS, ESTROGEN; SKIN; TRANSCRIPTIONAL ACTIVATION; WOUND HEALING;

EID: 64649101920     PISSN: 15438384     EISSN: 15438392     Source Type: Journal    
DOI: 10.1021/mp800206b     Document Type: Article

References (51)

1. Dahlman-Wright, K.; Cavailles, V.; Fuqua, S. A.; Jordan, V. C.; Katzenellenbogen, J. A.; Korach, K. S.; Maggi, A.; Muramatsu, M.; Parker, M. G.; Gustafsson, J. A. International Union of Pharmacology. LXIV. Estrogen Receptors. Pharmacol. Rev. 2006,58, 773-781.
2. Deroo, B. J.; Korach, K. S. Estrogen Receptors and Human Disease. J. Clin. Invest. 2006, 116, 561-570.
3. Maggi, A.; Ciana, P.; Belcredito, S.; Vegeto, E. Estrogens in the Nervous System: Mechanisms and Nonreproductive Functions. Annu. Rev. Physiol. 2004, 66, 291-313.
4. Moriarty, K.; Kim, K. H.; Bender, J. R. Minireview: Estrogen Receptor-mediated Rapid Signaling. Endocrinology 2006, 147, 5557-5563.
5. Heldring, N.; Pike, A.; Andersson, S.; Matthews, J.; Cheng, G.; Hartman, J.; Tujague, M.; Strom, A.; Treuter, E.; Warner, M.; Gustafsson, J. A. Estrogen Receptors: How do They Signal and What Are Their Targets. Physiol. Rev. 2007, 87, 905-931.
6. Prossnitz, E. R.; Arterburn, J. B.; Smith, H. O.; Oprea, T. I.; Sklar, L. A.; Hathaway, H. J. Estrogen Signaling through the Trans-membrane G Protein-coupled Receptor GPR30. Annu. Rev. Physiol. 2008, 70, 165-190.
7. Vegeto, E.; Pollio, G.; Pellicciari, C.; Maggi, A. Estrogen and Progesterone Induction of Survival of Monoblastoid Cells Undergoing TNF-alpha Induced Apoptosis. FASEBJ. 1999,13, 793-803.
8. Vegeto, E.; Bonincontro, C.; Pollio, G.; Sala, A.; Viappiani, S.; Nardi, F.; Brusadelli, A.; Viviani, B.; Ciana, P.; Maggi, A. Estrogen Prevents the Lipopolysaccharide-induced Inflammatory Response in Microglia. J. Neurosci. 2001, 21, 1809-1818.
9. Ashcroft, G. S.; Dodsworth, J.; van Boxtel, E.; Tarnuzzer, R. W.; Horan, M. A.; Schultz, G. S.; Ferguson, M. W. Estrogen Accelerates Cutaneous Wound Healing Associated with an Increase in TGF-β1 Levels. Nat. Med. 1997, 5, 1209-1215.
10. Hardman, M. J.; Emmerson, E.; Campbell, L.; Ashcroft, G. S. zelective Estrogen Receptor Modulators Accelerate Cutaneous Wound Healing in Ovariectomized Female Mice. Endocrinology 2008, 149, 551-557.
11. Ashcroft, G. S.; Mills, S. J.; Lei, K.; Gibbons, L.; Jeong, M.-J.; Taniguchi, M.; Burow, M.; Horan, M. A.; Wahl, S. M.; Nakayama, T. Estrogen Modulates Cutaneous Wound Healing by Downregu-lating Macrophage Migration Inhibitory Factor. J. Clin. Invest. 2003, 111, 1309-1318.
12. Fujimoto, J.; Hori, M.; Ichigo, S.; Tamaya, T. Ovarian Steroids Regulate the Expression of Basic Fibroblast Growth Factor and Its mRNA in Fibroblasts Derived from Uterine Endometrium. Ann. Clin. Biochem. 1997, 54, 91-96.
13. Shanker, G.; Sorci-Thomas, M.; Adams, M. R. Estrogen Modulates the Inducible Expression of Platelet-derived Growth Factor mRNA by Monocyte/Macrophages. Life Sci. 1995, 56, 499-507.
14. Pirila, E.; Ramamurthy, N.; Maisi, P.; McClain, S.; Kucine, A.; Wahlgren, J.; Golub, L. M.; Salo, T.; Sorsa, T. Wound Healing in Ovariectomized Rats: Effects of Chemically Modified Tetracycline (CMT-8) and Estrogen on Matrix Metalloproteinases-8,-13 and Type I Collagen Expression. Curr. Med. Chem. 2001, 8, 281-294.
15. Sato, T.; Ito, A.; Mori, Y.; Yamashita, K.; Hayakawa, T.; Nagase,H. Hormonal Regulation of Collagenolysis in Uterine Cervical Fibroblasts. Modulation of Synthesis of Procollagenase, Pros-tromelysin and Tissue Inhibitor of Metalloproteinases (TIMP) by Progesterone and Oestradiol-17 beta. Biochem. J. 1991, 275, 645-650.
16. Pirila, E.; Parikka, M.; Ramamurthy, N. S.; Maisi, P.; McClain, S.; Kucine, A.; Tervahartiala, T.; Prikk, K.; Golub, L. M.; Salo, T.; Sorsa, T. Chemically Modified Tetracycline (CMT-8) and Estrogen Promote Wound Healing in Ovariectomized Rats: Effects on Matrix Metalloproteinase-2, Membrane Type 1 Matrix Met-alloproteinase, and Laminin-5 gamma2-Chain. Wound Repair Regen. 2002, 10, 38-51.
17. Bodor, N. Designing Safer Drugs Based on the Soft Drug Approach. Trends Pharmacol. Sci. 1982, 5, 53-56.
18. Graffner-Nordberg, M.; Sjodin, K.; Tunek, A.; Hallberg, A. Synthesis and Enzymatic Hydrolysis of Esters, Constituting Simple Models of Soft Drugs. Chem. Pharm. Bull. (Tokyo) 1998, 46, 591-601.
19. Laurent, H.; Gerhards, E.; Wiechert, R. New Biologically Active Pregnan-21-oic Acid Esters. J. Steroid Biochem. 1975, 6, 185-192.
20. Lee, H. J.; Soliman, M. R. I. Antiinflammatory Steroids Without Pituitary Adrenal Suppression. Science 1982, 215, 989-991.
21. Bucourt, R.; Vignau, Mlli, V.; Richard-Foy, H.; Geynet, C.; Secco-Millet, C.; Redeuilh, G.; Baulieu, E. New Biospecific Adsorbents for the Purification of Estradiol Receptor. J. Biol. Chem. 1978, 253, 8221-8228.
22. Labaree, D. C.; Reynolds, T. Y.; Hochberg, R. B. Estradiol-16α- carboxylic Acid Esters as Locally Active Estrogens. J. Med. Chem. 2001, 44, 1802-1814.
23. Gao, H.; Katzenellenbogen, J. A.; Garg, R.; Hansch, C. Comparative QSAR Analysis of Estrogen Receptor Ligands. Chem. Rev. 1999, 99, 723-744.
24. Kappus, H.; Bolt, H. M.; Remmer, H. Affinity of Ethynyl-estradiol and Mestranol for the Uterine Estrogen Receptor and for the Microsomal Mixed Function Oxidase of the Liver. J. Steroid Biochem. 1973, 4, 121-128.
25. Buzby, G. C., Jr.; Smith, H. Ethynylating 17-oxo Steroidal Phenols. U.S. (1972), 5 pp. CODEN: USXXAM US 3646076 19720229. Application: US 70-42880 19700602.
26. Wust, F.; Spies, H.; Johannsen, B. Synthesis of 17αtuted Mercaptoalkynyl Derivatives of 3,17α-Estradiol. Tetrahedron Lett. 1997, 38, 2931-2932.
27. Foy, N.; Stéphan, E.; Vessieres, A.; Salomon, E.; Heldt, J.-M.; Huche, M.; Jaouen, G. Synthesis, Receptor Binding, Molecular Modeling, and Proliferative Assays of a Series of 17α-Arylestradiols. ChemBioChem 2003, 4, 494-503.
28. Miller, T. C.; Christiansen, R. G. Dependence of the Rate, Reversibility, and Stereoselectivity of 17-Ketosteroid Alkynylation on the Alkyne and on the Alkali Metal. J. Org. Chem. 1967, 32, 2781-2786.
29. Marini Bettolo, R.; Tsai, C. S. J.; Tsai, Y. R. T.; Wiesner, K. A One Sstep Synthesis of 17α-Hydroxy Cardenolides and Isocarde-nolides from C17 Steroidal Ketones. Heterocycles 1981, 15, 305-308.
30. Being a diastereomeric mixture no spectroscopic data are presented.
31. Kwon, J. H.; Katz, L. E.; Liljestrand, H. M. Modeling Binding Equilibrium in a Competitive Estrogen Receptor Binding Assay. Chemosphere 2007, 69, 1025-1031.
32. Yoshino, T.; Kato, F.; Takeyama, H.; Nakai, M.; Yakabe, Y.; Matsunaga, T. Development of a Novel Method for Screening of Estrogenic Compounds Using Nano-Sized Bacterial Magnetic Particles Displaying Estrogen Receptor. Anal. Chim. Acta 2005, 532, 105-111.
33. Rich, R. L.; Hoth, L. R.; Geoghegan, K. F.; Brown, T. A.; Le Motte, P. K.; Simons, S. P.; Hensley, P.; Myszka, D. G. Kinetic Analysis of Estrogen Receptor/Ligand Interactions. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 8562-8567.
34. Matthews, J.; Celius, T.; Halgren, R.; Zacharewski, T. Differential Estrogen Receptor Binding of Estrogenic Substances: a Species Comparison. J. Steroid Biochem. Mol. Biol. 2000, 74, 223-234.
35. Kuiper, G. G. J. M.; Lemmen, J. G.; Carlsson, B.; Corton, J. C.; Safe, S. H.; Van der Saag, P. T.; Van der Burg, B.; Gustafsson, J. A. Interaction of Estrogenic Chemicals and Phytoestrogens with Estrogen Receptor β. Endocrinology 1998, 139, 4252-4263.
36. Ciana, P.; Di Luccio, G.; Belcredito, S.; Pollio, G.; Vegeto, E.; Tatangelo, L.; Tiveron, C.; Maggi, A. Engineering of a Mouse for the In Vivo Profiling of Estrogen Receptor Activity. Mol. Endocrinol. 2001, 15, 1104-1113.
37. Ciana, P.; Raviscioni, M.; Mussi, P.; Vegeto, E.; Que, I.; Parker, M. G.; Lowik, C.; Maggi, A. In Vivo Imaging of Transcriptionally Active Estrogen Receptors. Nat. Med. 2003, 9, 82-86.
38. Giuliani, A. L.; Spisani, S.; Cavalletti, T.; Reali, E.; Melchiorri, L.; Ferrari, L.; Lanza, F.; Traniello, S. Fibroblasts Increase Adhesion to Neutrophils after Stimulation with Phorbol Ester and Cytokines. Cell. Immunol. 1993, 149, 208-222.
39. Gallucci, R. M.; Simeonova, P. P.; Matheson, J. M.; Kommineni, C.; Guriel, J. L.; Sugawara, T.; Luster, M. I. Impaired Cutaneous Wound Healing in Interleukin-6-deficient and Immunosuppressed Mice. FASEB J. 2000, 14, 2525-2531.
40. VanBrocklin, H. F.; Carlson, K. E.; Katzenellenbogen, J. A.; Welch, M. J. 16β-([18F]Fluoro)Estrogens: Systematic Investigation of a New Series of Fluorine-18-labeled Estrogens as Potential Imaging Agents for Estrogen-Receptor-Positive Breast Tumors. J. Med. Chem. 1993, 56, 1619-1629.
41. Boucheau, V.; Renaud, M.; Rolland de Ravel, M.; Mappus, E.; Cuilleron, C. Y. Proton and Carbon-13 Nuclear Magnetic Resonance Spectroscopy of Diastereoisomeric 3-and 17β-Tetrahy-dropyranyl ether Derivatives of Estrone and Estradiol. Steroids 1990, 55, 209-221.
42. Guay, B.; Deslongchamps, P. Cascade Polycyclization: Exploration of a Convergent Route to Access Various Tricyclic and Tetracyclic Products Related to Sterols. J. Org. Chem. 2003, 68, 6140-6148.
43. Roush, W. R.; Barda, D. A.; Limberakis, C.; Kunz, R. K. Studies on the Synthesis of the Quartromicins: Partial Stereochemical Assignment of Quartromicins A3 and D3 and Diastereoselective Synthesis of the Endo-and Exo-Spirotetronate Subunits. Tetrahedron 2002, 58, 6433-6454.
44. Kalivretenos, A.; Stille, J. K.; Hegedus, L. S. Synthesis of β-Resorcylic Macrolides via Organopalladium Chemistry. Application to the Total Synthesis of (S)-Zearalenone. J. Org. Chem. 1991, 56, 2883-2894.
45. Macaulay, S. R. Isomerization of Internal Triple Bonds of Alkyn-1-ols with Sodium Hydride in 1,3-Diaminopropane. J. Org. Chem. 1980, 45, 734-735.
46. Denmark, S. E.; Yang, S. M. Intramolecular Silicon-Assisted Cross-Coupling Reactions: General Synthesis of Medium-Sized Rings Containing a 1,3-cis-cis Diene Unit. J. Am. Chem. Soc. 2002, 124, 2102-2103.
47. Abrams, S. R.; Shaw, A. C. Triple-bond Isomerizations: 2-to 9-Decyn-1-ol. Org. Synth. 1988, 66, 127-131.
48. 2O/petr0oleum ether = 20/80, viscous oil, 80% yield) before hydrogenation and TBDMS removal.
49. Amadasi, A.; Mozzarelli, A.; Meda, C.; Maggi, A.; Cozzini, P., Identification of Xenoestrogens in Food Additives by an Integrated In Silico and In Vitro Approach Toxicol. Sci., in press.
50. Capra, V.; Veltri, A.; Foglia, C; Crimaldi, L.; Habib, A.; Parenti, M.; Rovati, G. E. Mutational Analysis of the Highly Conserved ERY Motif of the Thromboxane A2 Receptor: Alternative Role in G Protein-coupled Receptor Signaling. Mol. Pharmacol. 2004, 66, 880-889.
51. Biserni, A; Giannessi, F; Sciarroni, A. F.; Milazzo, F. M.; Maggi, A; Ciana, P. In Vivo Imaging reveals Selective Peroxisome Proliferator Activated Receptor Modulator Activity of the Synthetic Ligand 3-(1-(4-chlorobenzyl)-3-t- butylthio-5-isopropylindol-2-yl)-2,2-dimethylpropanoic acid (MK-886). Mol. Pharmacol. 2008, 75, 1434-1443.