Novel derivatives of 1,3,4-oxadiazoles are potent mitostatic agents featuring strong microtubule depolymerizing activity in the sea urchin embryo and cell culture assays

European Journal of Medicinal Chemistry

Volumn 45, Issue 5, 2010, Pages 1683-1697

  Kiselyov, Alex S ^a   Semenova, Marina N ^b   Chernyshova, Natalya B ^c   Leitao, Andrei ^d   Samet, Alexandr V ^c   Kislyi, Konstantine A ^c   Raihstat, Mikhail M ^c   Oprea, Tudor ^d   Lemcke, Heiko ^e   Lantow, Margaréta ^e   Weiss, Dieter G ^e   Ikizalp, Nazli N ^f   Kuznetsov, Sergei A ^e   Semenov, Victor V ^c,f  

^a DeCODE Chemistry & Biostructures   (United States)

^b KOL TSOV INSTITUTE OF DEVELOPMENTAL BIOLOGY   (Russian Federation)

^c N D ZELINSKY INSTITUTE OF ORGANIC CHEMISTRY   (Russian Federation)

^d UNIVERSITY OF NEW MEXICO   (United States)

^e UNIVERSITY OF ROSTOCK   (Germany)

^f Chemical Block Ltd   (Cyprus)

Author keywords

1,3,4 Oxadiazoles; anti mitotic agent; Cancer; Combretastatin; Microtubules; Sea urchin embryo; Tubulin

Indexed keywords

1,3,4 OXADIAZOLE DERIVATIVE; 2 (4 AMINOISOTHAZOLYL 3) 5 [(3,4 METHYLENEDIOXY)PHENYL]AMINO 1,3,4 OXADIAZOLE; 2 [[4 [(PYRIDYL 4)METHYL]AMINO]ISOTHIAZOLYL 3] 5 (3,3 ETHYLENEDIOXY)PHENYLAMINO 1,3,4 OXADIAZOLE; ANTIMITOTIC AGENT; COMBESTATIN DERIVATIVE; NOCODAZOLE; PODOPHYLLOTOXIN; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER CELL CULTURE; CELL ASSAY; CELL CYCLE ARREST; CELL CYCLE G2 PHASE; CELL PROLIFERATION; CELLULAR DISTRIBUTION; CONTROLLED STUDY; DEPOLYMERIZATION; DRUG CYTOTOXICITY; DRUG IDENTIFICATION; EMBRYO; EMBRYO CELL; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; MICROTUBULE ASSEMBLY; NONHUMAN; PHARMACOPHORE; PHENOTYPE; SEA URCHIN;

ANIMALS; ANTINEOPLASTIC AGENTS; BIOLOGICAL ASSAY; CELL CYCLE; CELL PROLIFERATION; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG SCREENING ASSAYS, ANTITUMOR; HUMANS; MICROTUBULES; MITOSIS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; OXADIAZOLES; PHENOTYPE; SEA URCHINS; STRUCTURE-ACTIVITY RELATIONSHIP; TUMOR CELLS, CULTURED;

EID: 77949492506     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2009.12.072     Document Type: Article

References (42)

1. Bray D. Cell Movements: From Molecules to Motility. second ed. (2001), Garland Publishing, New York
2. Jordan M.A., and Wilson L. Microtubules as a target for anticancer drugs. Nat. Rev. Cancer 4 (2004) 253-265
3. Kiselyov A.S., Balakin K., Tkachenko S.E., and Ivachtchenko A.V. Recent developments in discovery and development of antimitotic agents. Anti-Cancer Agents Med. Chem. 7 (2007) 189-208
4. Wordeman L., and Mitchison T.J. Dynamics of microtubule assembly in vivo. In: Hyams J.S., and Lloyd C.W. (Eds). Microtubules (1994), Wiley-Liss Inc., New York 287-301
5. Hamel E. Antimitotic natural products and their interactions with tubulin. Med. Res. Rev. 16 (1996) 207-231
6. Jordan A., Hadfield J.A., Laurence N.J., and McGown A.T. Tubulin as a target for anticancer drugs: agents which interact with the mitotic spindle. Med. Res. Rev. 18 (1998) 259-296
7. Kingston D.G.I. Tubulin-interactive natural products as anticancer agents. J. Nat. Prod. (2009) Jan 6 [Epub ahead of print]
8. Wilson L., Panda D., and Jordan M.A. Modulation of microtubule dynamics by drugs: a paradigm for the actions of cellular regulators. Cell Struct. Funct. 24 (1999) 329-335
9. Nogales E., Whittaker M., Milligan R.A., and Downing K.H. High-resolution model of the microtubule. Cell 96 (1999) 79-88
10. Diaz J.F., Strobe R., Engelborghs Y., Souto A.A., and Andreu J.M. Molecular recognition of Taxol by microtubules. Kinetics and thermodynamics of binding of fluorescent Taxol derivatives to an exposed site. J. Biol. Chem. 275 (2000) 26265-26276
11. Ravelli R.B.G., Gigant B., Curmi P.A., Jourdain I., Lachkar S., Sobel A., and Knossow M. Insight into tubulin regulation from a complex with colchicine and a stathmin-like domain. Nature 428 (2004) 198-202
12. Rowinsky E.K., Chaudhry V., Cornblath D.R., and Donehower R.C. Neurotoxicity of taxol. J. Natl. Cancer Inst. 15 (1993) 107-115
13. Cole S.P., Sparks K.E., Fraser K., Loe D.W., Grant C.E., Wilson G.M., and Deeley R.G. Pharmacological characterization of multidrug resistant MRP-transfected human tumor cells. Cancer Res. 54 (1994) 5902-5910
14. Lorico A., Rappa G., Flavell R.A., and Sartorelli A.C. Double knockout of the mrp gene leads to increased drug sensitivity in vitro. Cancer Res. 56 (1996) 5351-5355
15. Giannakakou P., Sackett D.L., Kang Y.K., Zhan Z., Buters J.T., Fojo T., and Poruchynsky M.S. Paclitaxel-resistant human ovarian cancer cells have mutant beta-tubulin that exhibit impaired paclitaxel-driven polymerization. J. Biol. Chem. 272 (1997) 17118-17125
16. Kavallaris M., Kuo D.Y.S., Burkhart C.A., Regl D.L., Norris M.D., Haber M., and Horwitz S.B. Taxol-resistant epithelial ovarian tumors are associated with altered expression of specific beta-tubulin isotypes. J. Clin. Invest. 100 (1997) 1282-1293
17. Pitot H.C., McElroy Jr. E.A., Reid J.M., Windebank A.J., Sloan J.A., Erlichman C., Bagniewski P.G., Walker D.L., Rubin J., Goldberg R.M., Adjei A.A., and Ames M.M. Phase I trial of Dolastatin-10 (NSC 376128) in patients with advanced solid tumors. Clin. Cancer Res. 5 (1999) 525-531
18. Nam N.-H. Combretastatin A-4 analogues as antimitotic antitumor agents. Curr. Med. Chem. 10 (2003) 1697-1722
19. Tron G.C., Pirali T., Sorba G., Pagliai F., Busacca S., and Genazzani A.A. Medicinal chemistry of combretastatin A-4: present and future directions. J. Med. Chem. 49 (2006) 3033-3044
20. Desbene S., and Giorgi-Renault S. Drugs that inhibit tubulin polymerization: the particular case of podophyllotoxin and analogues. Curr. Med. Chem. - Anti-Cancer Agents 2 (2002) 71-90
21. Ouyang X., Piatnitski E.L., Pattaropong V., Chen X., He H.-Y., Kiselyov A.S., Velankar A., Kawakami J., Labelle M., Smith II L., Lohman J., Lee S.P., Malikzay A., Fleming J., Gerlak J., Wang Y., Rosler R.L., Zhou K., Mitelman S., Camara M., Surguladze D., Doody J.F., and Tuma M.C. Oxadiazole derivatives as a novel class of antimitotic agents: synthesis, inhibition of tubulin polymerization, and activity in tumor cell lines. Bioorg. Med. Chem. Lett. 16 (2006) 1191-1196
22. Semenova M., Kiselyov A.S., and Semenov V.V. Sea urchin embryo as a model organism for the rapid functional screening of tubulin modulators. BioTechniques 40 (2006) 765-774. http://www.chemblock.com video illustrations are available at
23. Semenova M.N., Kiselyov A.S., Titov I.Y., Raihstat M.M., Molodtsov M., Grishchuk E., Spiridonov I., and Semenov V.V. In Vivo evaluation of indolyl glyoxamides in the sea urchin embryo model: correlation with in vitro tubulin dynamics effects. Chem. Biol. Drug Design 70 (2007) 485-490
24. Pettit G.R., Singh S.B., Boyd M.R., Hamel E., Pettit R.K., Schmidt J.M., and Hogan F. Antineoplastic agents. 291. Isolation and synthesis of combretastatins A-4, A-5, and A-6. J. Med. Chem. 38 (1995) 1666-1672
25. X. Ouyang, A. Kiselyov, X. Chen, H.-Y. He, J. Kawakami, V. Pattaropong, E. Piatnitski, M.C. Tuma, J. Kincaid, Heterocyclic compounds and their use as anticancer agents, Patent WO 2005/004818 A2, (2005).
26. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods 65 (1983) 55-63
27. Hawkins P.C.D., Skillman A.G., and Nicholls A. Comparison of shape-matching and docking as virtual screening tools. J. Med. Chem. 50 (2007) 74-82
28. Lin C.M., Singh S.B., Chu P.S., Dempcy R.O., Schmidt J.M., Pettit G.R., and Hamel E. Interactions of tubulin with potent natural and synthetic analogs of the antimitotic agent combretastatin: a structure-activity study. Mol. Pharmacol. 34 (1988) 200-208
29. Bacher G., Nickel B., Emig P., Vanhoefer U., Seeber S., Shandra A., Klenner T., and Beckers T. D-24851, a novel synthetic microtubule inhibitor, exerts curative antitumoral activity in vivo, shows efficacy toward multidrug-resistant tumor cells, and lacks neurotoxicity. Cancer Res. 61 (2001) 392-399
30. Couture A., Deniau E., Grandclaudon P., Lebrun S., Léonce S., Renard P., and Pfeiffer B. First synthesis and pharmacological evaluation of benzoindolizidine and benzoquinolizidine analogues of α- and β-peltatin. Bioorg. Med. Chem. 8 (2000) 2113-2125
31. http://eyesopen.com/products/applications/omega.html
32. http://eyesopen.com/products/applications/rocs.html
33. Fortin S., Moreau E., Lacroix J., Teulade J.-C., Patenaudea A., and Gaudreaulta R. N-Phenyl- N′-(2-chloroethyl)urea analogues of combretastatin A-4: is the N-phenyl-N′-(2-chloroethyl)urea pharmacophore mimicking the trimethoxy phenyl moiety. Bioorg. Med. Chem. Lett. 17 (2007) 2000-2004
34. Nguyen T.L., McGrath C., Hermone A.R., Burnett J.C., Zaharevitz D.W., Day B.W., Wipf P., Hamel E., and Gussio R. A common pharmacophore for a diverse set of colchicine site inhibitors using a structure-based approach. J. Med. Chem. 48 (2005) 6107-6116
35. Chaudhary A., Pandeya S.N., Kumar P., Sharma P.P., Gupta S., Soni N., Verma K.K., and Bhardwaj G. Combretastatin A-4 analogs as anticancer agents. Mini Rev. Med. Chem. 7 (2007) 1186-1205
36. Ouyang X., Chen X., Piatnitskii E.L., Kiselyov A.S., He H.-Y., Mao Y., Pattaropong V., Yu Y., Kim K.H., Kincaid J., Smith II L., Wong W.C., Lee S.P., Milligan D.L., Malikzay A., Fleming J., Gerlak J., Dhanvanthri D., Doody J.F., Chiang H.-H., Patel S.N., Wang Y., Rosler R.L., Kussie P., Labelle M., and Tuma M.C. Synthesis and structure-activity relationships of 1,2,4-triazoles as a novel class of tubulin polymerization inhibitors. Bioorg. Med. Chem. Lett. 15 (2005) 5154-5159
37. McGann M.R., Almond H.R., Nicholls A., Grant J.A., and Brown F.K. Gaussian docking functions. Biopolymers 68 (2003) 76-90
38. Gewald K., and Belimann P. Syntese und reactionen von 4-aminoisothiazolen. Liebigs Ann. Chem. (1979) 1534-1546
39. Al-Haddad A., Shonn M.A., Redlich B., Blocker A., Burkhardt J.K., Yu H., Hammer III J.A., Weiss D.G., Steffen W., Griffiths G., and Kuznetsov S.A. Myosin Va bound to phagosomes binds to F-actin and delays microtubule-dependent motility. Mol. Biol. Cell. 12 (2001) 2742-2755
40. Kuznetsov S.A., Rodionov V.I., Bershadsky A.D., Gelfand V.I., and Rosenblat V.A. High molecular weight protein MAP2 promoting microtubule assembly in vitro is associated with microtubules in cells. Cell Biol. Int. Rep. 4 (1980) 1017-1024
41. Weiss D.G., Maile W., Wick R.A., and Steffen W. Video microscopy. In: Lacey A.J. (Ed). Light Microscopy in Biology. A Practical Approach. second ed. (1999), Oxford University Press, USA 73-105
42. Löwe J., Li H., Downing K.H., and Nogales E. Refined structure of áâ-tubulin at 3.5 Å. J. Mol. Biol. 313 (2001) 1045-1057