Human polymerase α inhibitors for skin tumors. Part 2. Modeling, synthesis and influence on normal and transformed keratinocytes of new thymidine and purine derivatives

Journal of Enzyme Inhibition and Medicinal Chemistry

Volumn 25, Issue 2, 2010, Pages 250-265

  Hltje, Monika ^a   Richartz, Anja ^b   Zdrazil, Barbara ^a   Schwanke, Anja ^b   Dugovic, Branislav ^b   Murruzzu, Caterina ^b   Reißig, Hans Ulrich ^b   Korting, Hans Christian ^c   Kleuser, Burkhard ^b   Hltje, Hans Dieter ^a   Schafer Korting, Monika ^b  

^a HEINRICH HEINE UNIVERSITY   (Germany)

^b FREIE UNIVERSITÄT BERLIN   (Germany)

^c LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

Author keywords

Human DNA polymerase; Keratinocytes; Kinases; Molecular dynamic simulations; Nucleoside analogs; Nucleoside transporters; Polymerase inhibitors

Indexed keywords

2 (4 BUTYL 3 HYDROXYPHENYLANILINO) 2' DEOXYADENOSINE; 2 [4 (4 METHYLPENTYL) 3 HYDROXYPHENYLANILINO] 2' DEOXYADENOSINE; 3' KETOTHYMIDINE; AMINO ACID; APHIDICOLIN; DICLOFENAC; DNA; DNA DIRECTED DNA POLYMERASE ALPHA; ENZYME INHIBITOR; FLUOROURACIL; MESSENGER RNA; NUCLEOTIDE TRANSPORTER; PHOSPHOTRANSFERASE; PURINE DERIVATIVE; THYMIDINE DERIVATIVE; UNCLASSIFIED DRUG;

ACTINIC KERATOSIS; APOPTOSIS; BINDING AFFINITY; BIOTRANSFORMATION; CANCER CELL CULTURE; CELL CYCLE; CELL DEATH; CELL PROLIFERATION; CELLULAR DISTRIBUTION; CONFERENCE PAPER; CONTROLLED STUDY; CYTOTOXICITY; DNA SYNTHESIS; DRUG SYNTHESIS; ENZYME ACTIVATION; ENZYME INHIBITION; ENZYME STRUCTURE; GENE EXPRESSION; GEOMETRY; HUMAN; HUMAN CELL; IN VITRO STUDY; KERATINOCYTE; MOLECULAR DOCKING; MOLECULAR DYNAMICS; MOLECULAR INTERACTION; MOLECULAR MODEL; PHYSICAL CHEMISTRY; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; SKIN CANCER; SQUAMOUS CELL CARCINOMA;

APHIDICOLIN; APOPTOSIS; CARCINOMA, SQUAMOUS CELL; CELL LINE, TUMOR; CELL PROLIFERATION; DNA POLYMERASE I; HUMANS; KERATINOCYTES; KERATOSIS, ACTINIC; MODELS, CHEMICAL; MODELS, MOLECULAR; NECROSIS; NUCLEIC ACID SYNTHESIS INHIBITORS; NUCLEOTIDE TRANSPORT PROTEINS; PROTEIN BINDING; PURINES; SKIN NEOPLASMS; THYMIDINE;

EID: 77949479562     PISSN: 14756366     EISSN: 14756374     Source Type: Journal    
DOI: 10.3109/14756360903059579     Document Type: Conference Paper

References (37)

1. Jorizzo J. Topical treatment of actinic keratosis with fluorouracil: is irritation associated with efficacy? J Drugs Dermatol 2004; 3:21-26
2. Rhodes LE, de Rie M, Enstrom Y, Groves R, Morken T, Goulden V, et al. Photodynamic therapy using topical methyl aminolevulinate vs surgery for nodular basal cell carcinoma: results of a multicenter randomized prospective trial. Arch Dermatol 2004;140:17-23.
3. Rivers JK, Arlette J, Shear N, Guenther L, Carey W, Poulin Y. Topical treatment of actinic keratoses with 3.0% diclofenac in 2.5% hyaluronan gel. Br J Dermatol 2002;146:94-100.
4. Lebwohl M, Dinehart S, Whiting D, Lee PK, Tawfik N, Jorizzo J, et al. Imiquimod 5% cream for the treatment of actinic keratosis: results from two phase III, randomized, double-blind, parallel group, vehiclecontrolled trials. J Am Acad Dermatol 2004; 50:714-721
5. Maeda N, Kokai Y, Ohtani S, Sahara H, Kuriyama I, Kamisuki S, et al. Anti-tumor effects of dehydroaltenusin, a specific inhibitor of mammalian DNA polymerase alpha. Biochem Biophys Res Commun 2007;352:390-396
6. Kuriyama I, Musumi K, Yonezawa Y, Takemura M, Maeda N, Iijima H, et al. Inhibitory effects of glycolipids fraction from spinach on mammalian DNA polymerase activity and human cancer cell proliferation. J Nutr Biochem 2005;16:594-601.
7. Maeda N, Kokai Y, Ohtani S, Sahara H, Hada T, Ishimaru C, et al. Antitumor effects of the glycolipids fraction from spinach which inhibited DNA polymerase activity. Nutr Cancer 2007;57:216-223
8. Matsubara K, Saito A, Tanaka A, Nakajima N, Akagi R, Mori M, Mizushina Y. Catechin conjugated with fatty acid inhibits DNA polymerase and angiogenesis. DNA Cell Biol 2006;25:95-103.
9. Matsubara K, Saito A, Tanaka A, Nakajima N, Akagi R, Mori M, et al. Epicatechin conjugated with fatty acid is a potent inhibitor of DNA polymerase and angiogenesis. Life Sci 2007;80:1578-1585
10. Gandhi V, Huang P, Chapman AJ, Chen F, Plunkett W. Incorporation of fludarabine and 1-beta-D-arabinofuranosylcytosine 5'-triphosphates by DNA polymerase alpha: affinity, interaction, and consequences. Clin Cancer Res 1997;3:1347-1355
11. Jiang HY, Hickey RJ, Abdel-Aziz W, Malkas LH. Effects of gemcitabine and araC on in vitro DNA synthesis mediated by the human breast cell DNA synthesome. Cancer Chemother Pharmacol 2000;45:320-328
12. Richartz A, Holtje M, Brandt B, Schafer-Korting M, Holtje HD. Targeting human DNA polymerase alpha for the inhibition of keratinocyte proliferation. Part 1.Homology model, active site architecture and ligand binding. J Enzyme Inhib Med Chem 2008;23:94-100.
13. O'Dwyer PJ, Moyer JD, Suffness M, Harrison SD Jr, Cysyk R, Hamilton TC, et al. Antitumor activity and biochemical effects of aphidicolin glycinate (NSC 303812) alone and in combination with cisplatin in vivo. Cancer Res 1994;54:724-729
14. Julia M, Baillarge M.Keto derivs. of aminophenols by the Friedel-Crafts and the Fries reactions. Bull Chim Soc Fr 1952:639-642
15. Hoffer M. Alpha-thymidine. Chem Ber 1960;93:2777-2781
16. Lan T, McLaughlin LW. Minor groove hydration is critical to the stability of DNA duplexes. J Am Chem Soc 2000;122:6512-6513
17. Vogler R, Sauer B, Kim DS, Schafer-Korting M, Kleuser B. Sphingosine-1-phosphate and its potentially paradoxical effects on critical parameters of cutaneous wound healing. J Invest Dermatol 2003;120:693-700.
18. Gysler A, Lange K, Korting HC, Schafer-Korting M. Prednicarbate biotransformation in human foreskin keratinocytes and fibroblasts. Pharm Res 1997;14:793-797
19. Liebsch M, Spielmann H. 3T3 NRU Phototoxicity Assay. Available at http://ecvam-dbalmjrcceceuint/public-view-doccfm?id=736F27E9E9F 7A9D869FB48087878D2497180BB0BC12CB10496CDA74B54630A05A329 1B895581F634, 1998.
20. Vermes I, Haanen C, Richel DJ, Schaafsma MR, Kalsbeek-Batenburg E, Reutelingsperger CP. Apoptosis and secondary necrosis of lymphocytes in culture. Acta Haematol 1997;98:8-13.
21. Manggau M, Kim DS, Ruwisch L, Vogler R, Korting HC, Schafer-Korting M, et al. 1Alpha,25-dihydroxyvitamin D3 protects human keratinocytes from apoptosis by the formation of sphingosine-1-phosphate. J Invest Dermatol 2001;117:1241-1249
22. Zdrazil B, Holtje M, Schwanke A, Schmitz B, Schafer-Korting M, Holtje H-D.Molecular modeling studies of new potential human DNA polymerase alpha inhibitors. 2009; submitted.
23. Hansske F, Madej D, Robins MJ. 2' and 3'-Ketonucleosides and their arabino and xylo reduction products: convenient access via selective protection and oxidation of ribonucleosides. Tetrahedron 1984;40:125-135
24. Sharma M, Bobek M. Synthesis of 2′,3′-dideoxy-3′- methylene pyrimine nucleosides as potential anti-AIDS agents. Tetrahedron Lett 1990;31:5839-5842
25. Samano V, Robins MJ. Nucleic acid related compounds. 60. Mild periodinane oxidation of protected nucleosides to give 2'-,and 3'- ketonucleosides. The first isolation of a purine 2'-deoxy-3'-ketonucleoside derivative. J Org Chem 1990;55:5186-5188
26. Wright GE, Dudycz LW, Kazimierczuk Z, Brown NC, Khan NN. Synthesis, cell growth inhibition, and antitumor screening of 2-(pn- butylanilino)purines and their nucleoside analogues. J Med Chem 1987;30:109-116
27. Frieden M, Avino A, Eritja R. Convenient synthesis of 8-amino- 2'-deoxyadenosine. Nucleosides Nucleotides Nucleic Acids 2003;22:193-202.
28. Koshkin AA. Syntheses and base-pairing properties of locked nucleic acid nucleotides containing hypoxanthine, 2,6-diaminopurine, and 2-aminopurine nucleobases. J Org Chem 2004;69:3711-3718
29. Fedorocko P, Hoferova Z, Hofer M, Brezani P. Administration of liposomal muramyl tripeptide phosphatidylethanolamine (MTP-PE) and diclofenac in the combination attenuates their anti-tumor activities. Neoplasma 2003;50:176-184
30. Hoferova Z, Fedorocko P, Hofmanova J, Hofer M, Znojil V, Minksova K, et al. The effect of nonsteroidal antiinflammatory drugs ibuprofen, flurbiprofen, and diclofenac on in vitro and in vivo growth of mouse fibrosarcoma. Cancer Invest 2002;20:490-498
31. Boucher PD, Im MM, Freytag SO, Shewach DS. A novel mechanism of synergistic cytotoxicity with 5-fluorocytosine and ganciclovir in double suicide gene therapy. Cancer Res 2006;66:3230-3237
32. Haberland A, Schreiber S, Maia CS, Rubbelke MK, Schaller M, Korting HC, et al. The impact of skin viability on drug metabolism and permeation - BSA toxicity on primary keratinocytes. Toxicol In Vitro 2006;20:347-354
33. Edelson RE, Gorycki PD, MacDonald TL. The mechanism of aphidicolin bioinactivation by rat liver in vitro systems. Xenobiotica 1990;20:273-287
34. Vogt T, McClelland M, Jung B, Popova S, Bogenriede T, Becker B, et al. Progression and NSAID-induced apoptosis in malignant melanomas are independent of cyclooxygenase II. Melanoma Res 2001;11:587-599
35. Rodriguez CO Jr, Mitchell BS, Ayres M, Eriksson S, Gandhi V. Arabinosylguanine is phosphorylated by both cytoplasmic deoxycytidine kinase and mitochondrial deoxyguanosine kinase. Cancer Res 2002;62:3100-3105
36. Baron JM, Holler D, Schiffer R, Frankenberg S, Neis M, Merk HF, et al. Expression of multiple cytochrome p450 enzymes and multidrug resistance-associated transport proteins in human skin keratinocytes. J Invest Dermatol 2001;116:541-548
37. Schiffer R, Neis M, Holler D, Rodriguez F, Geier A, Gartung C, et al. Active influx transport is mediated by members of the organic anion transporting polypeptide family in human epidermal keratinocytes. J Invest Dermatol 2003;120:285-291