Design, synthesis and bioevaluation of novel maleamic amino acid ester conjugates of 3,5-bisarylmethylene-4-piperidones as cytostatic agents

Bioorganic and Medicinal Chemistry Letters

Volumn 19, Issue 22, 2009, Pages 6364-6367

  Youssef, Dani ^a,b   Potter, Elizabeth ^b   Jha, Mamta ^b   De Clercq, Erik ^c   Balzarini, Jan ^c   Stables, James P ^d   Jha, Amitabh ^b  

^a Universite Sainte Anne   (Canada)

^b ACADIA UNIVERSITY   (Canada)

^c REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

^d NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE   (United States)

Author keywords

3,5 Bisarylmethylene 4 piperidones; Anticancer; Cytostatic activity; QSAR; Topoisomerase inhibitions

Indexed keywords

3,5 BISARYLMETHYLENE 4 PIPERIDONE; ACICLOVIR; AMINO ACID DERIVATIVE; ANTINEOPLASTIC AGENT; CYTOSTATIC AGENT; DNA TOPOISOMERASE (ATP HYDROLYSING); MALEAMIC AMINO ACID ESTER; MELPHALAN; PIPERIDONE DERIVATIVE; THIOL; TOPOISOMERASE IIALPHA; TRACE ELEMENT; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; APOPTOSIS; ARTICLE; BIOEQUIVALENCE; CANCER CELL; CANCER CELL CULTURE; CLINICAL EVALUATION; CONTROLLED STUDY; CYTOSTASIS; CYTOTOXICITY; DRUG BIOAVAILABILITY; DRUG CONJUGATION; DRUG DELIVERY SYSTEM; DRUG EFFICACY; DRUG POTENCY; DRUG SELECTIVITY; DRUG SYNTHESIS; ENZYME INHIBITION; HUMAN; HUMAN CELL; LEUKEMIA CELL; MOUSE; NONHUMAN; QUANTITATIVE STRUCTURE ACTIVITY RELATION; T LYMPHOCYTE;

ANIMALS; ANTINEOPLASTIC AGENTS; ANTIVIRAL AGENTS; BINDING SITES; CELL LINE; CELL LINE, TUMOR; CELL SURVIVAL; CRYSTALLOGRAPHY, X-RAY; CYTOSTATIC AGENTS; DRUG DESIGN; DRUG SCREENING ASSAYS, ANTITUMOR; ESTERS; HELA CELLS; HUMANS; LEUKEMIA L1210; MICE; PIPERIDONES; STEREOISOMERISM; SUBSTRATE SPECIFICITY; T-LYMPHOCYTES;

MURINAE;

EID: 71049177485     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2009.09.069     Document Type: Article

References (34)

1. Jha A., and Duffield K.M. Indian J. Chem., Sect. B 45 (2006) 2313
2. Dimmock J.R., Jha A., Zello G.A., Sharma R.K., Shrivastav A., Selvakumar P., Allen T.M., Santos C.L., Balzarini J., De Clercq E., Manavathu E.K., and Stables J.P. J. Enzyme Inhib. Med. Chem. 18 (2003) 325
3. Dimmock J.R., Jha A., Kumar P., Zello G.A., Quail J.W., Oloo E.O., Oucharek J.J., Pasha M.K., Seitz D., Sharma R.K., Allen T.M., Santos C.L., Manavathu E.K., De Clercq E., Balzarini J., and Stables J.P. Eur. J. Med. Chem. 37 (2002) 35
4. Dimmock J.R., Jha A., Zello G.A., Quail J.W., Oloo E.O., Nienaber K.H., Kowalczyk E.S., Allen T.M., Santos C.L., De Clercq E., Balzarini J., Manavathu E.K., and Stables J.P. Eur. J. Med. Chem. 37 (2002) 961
5. Jha A., Mukherjee C., Prasad A.K., Parmar V.S., Clercq E.D., Balzarini J., Stables J.P., Manavathu E.K., Shrivastav A., Sharma R.K., Nienaber K.H., Zello G.A., and Dimmock J.R. Bioorg. Med. Chem. 15 (2007) 5854
6. Jha A., and Dimmock J.R. Synth. Commun. 33 (2003) 1211
7. Dimmock J.R., Arora V.K., Quail J.W., Pugazhenthi U., Allen T.M., Kao G.Y., and De Clercq E. J. Pharm. Sci. 83 (1994) 1124
8. Makarov M.V., Odinets I.L., Lyssenko K.A., Rybalkina E.Y.B.A., Kosilkin I.V., Antipin M.Y., and Timofeeva T.V. J. Heterocycl. Chem. 45 (2008) 729
9. Pati H.N., Das U., Quail J.W., Kawase M., Sakagami H., and Dimmock J.R. Eur. J. Med. Chem. 43 (2008) 1
10. Pati H.N., Das U., Das S., Bandy B., De Clercq E., Balzarini J., Kawase M., Sakagami H., Quail J.W., Stables J.P., and Dimmock J.R. Eur. J. Med. Chem. 44 (2009) 54
11. Das U., Alcorn J., Shrivastav A., Sharma R.K., De Clercq E., Balzarini J., and Dimmock J.R. Eur. J. Med. Chem. 42 (2007) 71
12. Das U., Selvakumar P., Sharma R.K., Haas T.A., and Dimmock J.R. J. Enzyme Inhib. Med. Chem. 22 (2007) 451
13. Das U., Das S., Bandy B., Stables J.P., and Dimmock J.R. Bioorg. Med. Chem. 16 (2008) 3602
14. Dimmock J.R., Arora V.K., Wonko S.L., Hamon N.W., Quail J.W., Jia Z., Warrington R.C., Fang W.D., and Lee J.S. Drug Des. Deliv. 6 (1990) 183
15. Dimmock J.R., Padmanilayam M.P., Puthucode R.N., Nazarali A.J., Motaganahalli N.L., Zello G.A., Quail J.W., Oloo E.O., Kraatz H.B., Prisciak J.S., Allen T.M., Santos C.L., Balzarini J., De Clercq E., and Manavathu E.K. J. Med. Chem. 44 (2001) 586
16. Makarov M.V., Rybalkina E.Y., Roschenthaler G.V., Short K.W., Timofeeva T.V., and Odinets I.L. Eur. J. Med. Chem. 44 (2009) 2135
17. McClendon A.K., and Osheroff N. Mutat. Res. 623 (2007) 83
18. Deweese J.E., and Osheroff N. Nucleic Acids Res. 37 (2009) 738
19. Burden D.A., and Osheroff N. Biochim. Biophys. Acta 1400 (1998) 139
20. Chen G.L., Yang L., Rowe T.C., Halligan B.D., Tewey K.M., and Liu L.F. J. Biol. Chem. 259 (1984) 13560
21. Duffield, K., Honours Thesis, Acadia University, 2004.
22. Wang J. Nat. Rev. Mol. Cell Biol. 3 (2002) 430
23. Champoux J.J. Annu. Rev. Biochem. 70 (2001) 369
24. Chene P., Rudloff J., Schoepfer J., Furet P., Meier P., Qian Z., Schlaeppi J.M., Schmitz R., and Radimerski T. BMC Chem. Biol. 9 (2009) 1
25. Colla L., De Clercq E., Busson R., and Vanderhaeghe H. J. Med. Chem. 26 (1983) 602
26. Beauchamp L.M., Orr G.F., Demiranda P., Burnette T., and Krenitsky T.A. Antiviral Chem. Chemother. 3 (1992) 157
27. Sinhababu A.K., and Thakker D.R. Adv. Drug. Delivery Rev. 19 (1996) 241
28. Breistøl K., Hendriks H.R., Berger D.P., Langdon S.P., Fiebig H.H., and Fodstad O. Eur. J. Cancer 34 (1998) 1602
29. Liwschitz Y., and Zilkha A. J. Am. Chem. Soc. 77 (1955) 1265
30. +.
31. Balzarini J., De Clerq E., Mertes M., Shugar D., and Torrence P.F. Biochem. Pharmacol. 31 (1982) 3673
32. ChemBioDraw, 11.0.1; CambridgeSoft: 2007.
33. Assays investigating the inhibition of TOPO IIα were carried out as per the protocol supplied by TopoGEN Inc., the source for purified human DNA TOPO IIα (p170 form) and pRYG DNA. The enzyme was incubated with the compound for 30 min at 37 °C. Subsequently SDS and proteinase K were added. The reaction was stopped with the appropriate TopoGEN stop buffer after 15 min of incubation. The assay and all appropriate controls were loaded on a 1% agarose gel in 1× TAE and run at 60 V for 2 h. The gel was then visualized using ethidium bromide staining. Compounds were assayed at 100 μM, decreasing the concentrations to 50 μM, 25 μM and 10 μM if compounds still exhibited inhibitory activity. All assays were completed in duplicate.
34. In: Stables J.P., and Kupferberg H.J. (Eds). Molecular and Cellular Targets for Antiepileptic Drugs (1997), John Libbey, London