Summary
Using the X-ray crystal structure of the human topoisomerase I (top1) – DNA cleavable complex and the Sybyl software package, we have developed a general model for the ternary cleavable complex formed with four protoberberine alkaloids differing in the substitution on the terminal phenyl rings and covering a broad range of the top1-poisoning activities. This model has the drug intercalated with its planar chromophore between the −1 and +1 base pairs flanking the cleavage site, with the nonplanar portion pointing into the minor groove. The ternary complexes were geometry-optimized and relative interaction energies, computed by using the Tripos force field, were found to rank in correct order the biological potency of the compounds; in addition, the model is also consistent with the top1-poisoning inactivity of berberine, a major prototype of the protoberberine alkaloids. The model might serve as a rational basis for elaboration of the most active compound as a lead structure, in order to develop more potent top1 poisons as next generation anti-cancer drugs.
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References
A.L. Okunade C.D. Hufford M.D. Richardson J.R. Petterson A.M. Clark (1994) J. Pharm. Sci., 83 404
B.K. Sarma V.B. Pandey G.D. Mishra U.P. Singh (1999) Folia Microbiol. 44 164 Occurrence Handle1:CAS:528:DyaK1MXkvFaqtLw%3D
M. Èeròáková D. Košt’álová V. Kettmann M. Plodová J. Tóth (2002) ArticleTitleDøímal J BMC Complement. Alternative Med. 2 1 Occurrence Handle10.1186/1472-6882-2-1
C.L. Kuo C.C. Chou B.Y.-M. Yung (1995) Cancer Lett. 93 193 Occurrence Handle10.1016/0304-3835(95)03809-B Occurrence Handle1:CAS:528:DyaK2MXmvVensb0%3D Occurrence Handle7621428
L. Orfila M. Rodriguez T. Colman M. Hasegawa M. Merentes F. Arvelo (2000) J Ethnopharmacol. 71 449 Occurrence Handle10.1016/S0378-8741(00)00177-X Occurrence Handle1:CAS:528:DC%2BD3cXlsFCjtLs%3D Occurrence Handle10940582
K. Iwasa M. Moriyasu T. Yamori T. Turuo D.U. Lee W. Wiegrebe (2001) J. Nat. Prod. 64 896 Occurrence Handle10.1021/np000554f Occurrence Handle1:CAS:528:DC%2BD3MXksVKlu7w%3D Occurrence Handle11473418
V. Kettmann D. Košt’álová S. Jantová M. Èeròáková Døímal (2004) J., Pharmazie 59 548
P. Pantazis B. Giovanella M.L. Rotenberg (1996) The Camptothecins: From Discovery to the Patient New York Academy of Sciences. New York.
T.K. Li E. Bathory E.J. LaVoie A.R. Srinivasan W.K. Olson L.L. Sauers L.F. Liu D.S. Pilch (2000) Biochemistry 39 7107 Occurrence Handle10.1021/bi000171g Occurrence Handle1:CAS:528:DC%2BD3cXjt1Wku7k%3D Occurrence Handle10852708
D.S. Pilch C. Yu D. Makhey E.J. LaVoie A.R. Srinivasan W.K. Olson R.R. Sauers K.J. Breslauer N.E. Geacintov L.F. Liu (1997) Biochemistry 36 12542 Occurrence Handle1:CAS:528:DyaK2sXmtFGhu78%3D Occurrence Handle9376359
J. Champoux J.C. Wang N.R. Cozarelli (1990) DNA Topology and its Biological Effects Cold Spring Harbor Laboratory Press. Cold Spring Harbor, NY 217–242
J.C. Wang (1996) ArticleTitleAnn. Rev Biochem 65 635 Occurrence Handle1:CAS:528:DyaK28XktFamur0%3D Occurrence Handle8811192
Y.H. Hsiang R. Hertzberg S. Hecht L.F. Liu (1985) ArticleTitleJ. Biol Chem 260 14873 Occurrence Handle1:CAS:528:DyaL2MXlsFemt7c%3D
A.J. Ryan S. Squires H.L. Strutt R.T. Johnson (1991) Nucleic Acids Res., 19 3295
R.M. Snapka P.A. Permana (1993) Bioessays 15 121 Occurrence Handle10.1002/bies.950150208 Occurrence Handle1:CAS:528:DyaK3sXit1Cksb0%3D Occurrence Handle8385943
I.W. Yang C.C. Chou B.I.M. Yung (1996) ArticleTitleNaunyn-Schiedeberg’s Arch Pharmacol. 354 102 Occurrence Handle1:STN:280:ByiD3M%2FlsVw%3D
Jantová S., Čipák L’., Čeròáková M., Košt’álová D., J. Pharm. Pharmacol., 55 (2003)
M.R. Redinbo L. Stewart P. Kuhn J.J. Champoux W.G.J. Hol (1998) Science 279 1504 Occurrence Handle10.1126/science.279.5356.1504 Occurrence Handle1:CAS:528:DyaK1cXhs1Kntro%3D Occurrence Handle9488644
G.S. Laco J.R. Collins B.T. Luke H. Kroth J.M. Sayer D.M. Jerina Y. Pommier (2002) Biochemistry 41 1428 Occurrence Handle10.1021/bi011774a Occurrence Handle1:CAS:528:DC%2BD38Xis1Okuw%3D%3D Occurrence Handle11814334
J.E. Kerrigan D.S. Pilch (2001) Biochemistry 40 9792 Occurrence Handle10.1021/bi010913l Occurrence Handle1:CAS:528:DC%2BD3MXlsVSrtbY%3D Occurrence Handle11502172
Y. Pommier G.S. Laco G. Kohlhagen J.M. Sayer H. Kroth D.M. Jerina (2000) ArticleTitleProc Natl. Acad. Sci. USA, 97 10739
B.L. Staker K. Hjerrild M.D. Feese C.A. Behnke L. Stewart (2002) ArticleTitleProc Natl. Acad. Sci. USA, 99 15387
M.W. Davidson I. Lopp S. Alexander W.D. Wilson (1977) Nucleic Acids Res., 4 2697
R.L. Jones A.C. Lanier R.A. Kiel W.D. Wilson (1980) Nucleic Acids Res., 8 1613
SYBYL: Tripos Associates Inc., St. Louis, MO; version 6.7
Y.-H. Hsiang R. Hertzberg S. Hecht L.F. Liu (1985) J Biol. Chem 260 14873 Occurrence Handle1:CAS:528:DyaL2MXlsFemt7c%3D Occurrence Handle2997227
R. Wang L. Lai S. Wang (2002) J. Comput-Aided Mol. Des. 16 11 Occurrence Handle10.1023/A:1016357811882 Occurrence Handle1:CAS:528:DC%2BD38XltlSqs7k%3D Occurrence Handle12197663
B.M. Kariuki W. Jones (1995) ArticleTitleActa Crystallogr. Sect C, 51 1234
F.H. Allen O. Kennard R. Taylor (1983) Acc. Chem. Res. 16 146 Occurrence Handle10.1021/ar00089a001 Occurrence Handle1:CAS:528:DyaL3sXktVCkur0%3D
G. Chillemi T. Castrignano A. Desideri (2001) Biophys J., 81 490
A. Adams J.M. Guss W.A. Denny L.P.G. Wakelin (2002) Nucleic Acids Res., 30 719
Berman, H.M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T.N., Weissig, H., Shindyalov, I.N., Bourne, P.E., Nucleic Acids Res., 28 (2000) 235, http:// www.rcsb.org/pdb/
D.S. Pilch C. Yu D. Makhey E.J. LaVoie A.R. Srinivasan W.K. Olson R.R. Sauers K.J. Breslauer N.E. Geracintov L.F. Liu (1997) Biochemistry 36 12542 Occurrence Handle1:CAS:528:DyaK2sXmtFGhu78%3D Occurrence Handle9376359
R. Wang L. Lai S. Wang (2002) J. Comput.-Aided Mol Des. 16 11 Occurrence Handle10.1023/A:1016357811882 Occurrence Handle1:CAS:528:DC%2BD38XltlSqs7k%3D Occurrence Handle12197663
K.V. Anis G. Kuttan R. Kuttan (1999) Pharm Pharmacol. Commun. 5 697 Occurrence Handle1:CAS:528:DC%2BD3cXhtFCjsLg%3D
Y. Kobayashi Y. Yamashita N. Fujii K. Takaboshi T. Kawakami M. Kawamura T. Mizukami H. Nakano (1995) Planta Med. 61 414 Occurrence Handle1:CAS:528:DyaK2MXpt1Ogs7o%3D Occurrence Handle7480201
T.-K. Li E. Bathory E.J. LaVoie A.R. Srinivasan W.K. Olson R.R. Sauers L.F. Liu D.S. Pilch (2000) Biochemistry, 39 7107
P. Krishnan K.F. Bastow (2000) Anti-Cancer Drug Des., 15 255
Y. Fan J.N. Weinstein K.W. Kohn L.M. Shi Y. Pommier (1998) J. Med. Chem. 41 2216 Occurrence Handle10.1021/jm9605445 Occurrence Handle1:CAS:528:DyaK1cXjtlynu7w%3D Occurrence Handle9632354
A. Palumbo B. Gatto S. Moro C. Sissi G. Zagotto (2002) ArticleTitleBiochim Biophys. Acta 1587 145 Occurrence Handle1:CAS:528:DC%2BD38XkslKjtbY%3D
M.M. Sanders A.A. Liu T.-K. Li H.-Y. Wu S.D. Desai Y. Mao E.H. Rubin E.J. LaVoie D. Makhey L.F. Liu (1998) ArticleTitleBiochem Pharmacol. 56 1157 Occurrence Handle1:CAS:528:DyaK1cXnt1Oht7w%3D
E. Chatelut J.P. Delord P. Canal (2003) ArticleTitleInvest New Drugs 21 141 Occurrence Handle10.1023/A:1023565227808 Occurrence Handle1:CAS:528:DC%2BD3sXjtlantrs%3D
P. Pantazis B. Giovanella M.L. Rotenberg (1996) The Camptothecins: From Discovery to the Patient New York Academy of Sciences New York 1–328
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Kettmann, V., Košt’álová, D. & Höltje, HD. Human topoisomerase I poisoning: docking protoberberines into a structure-based binding site model. J Comput Aided Mol Des 18, 785–796 (2004). https://doi.org/10.1007/s10822-004-7878-1
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DOI: https://doi.org/10.1007/s10822-004-7878-1