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Molecular Docking and Design of Novel Heterodimers of Donepezil and Huperzine Fragments as Acetylcholinesterase Inhibitors

HUANG Chu-Sheng ,  TU Wen-Tong ,  LUO Min ,  SHI Jian-Cheng

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Citation:  HUANG Chu-Sheng, TU Wen-Tong, LUO Min, SHI Jian-Cheng. Molecular Docking and Design of Novel Heterodimers of Donepezil and Huperzine Fragments as Acetylcholinesterase Inhibitors[J]. Chinese Journal of Structural Chemistry, 2016, 35(6): 839-848. doi: 10.14102/j.cnki.0254-5861.2011-0733 shu

Molecular Docking and Design of Novel Heterodimers of Donepezil and Huperzine Fragments as Acetylcholinesterase Inhibitors

  • 1.

    College of Chemistry and material Sciences, Guangxi Teachers Education University, Nanning 530001, China

    • 通讯作者: SHI Jian-Cheng,
摘要: To provide hints for the design of new acetylcholinesterase (AChE) inhibitors with higher potency and specificity, the binding modes of novel heterodimers comprised of donepezil and huperzine A fragments with AChE were explored by employing the docking simulations. The results show that the binding mode of S-17b (the most potent inhibitor in Ref. 2, i.e., Bioorg. Med. Chem. 2013, 21, 676-683) is clearly different from that of donepezil, while the binding modes of other heterodimers in Ref. 2 are the same as that of donepezil. In addition, based on the binding mode and structure modification of S-17b, two novel inhibitors (S-17b1 and S-17bb1) with much higher inhibitory potency than S-17b were obtained. Our design strategy was to replace the hupyridone moiety of S-17b with the bulky group, and to replace the dimethoxyindanone moiety of S-17b with more hydrophobic and bulky group with a highly positive charge, which would result in generating potent and selective AChE inhibitors.

English

  • 
    1. [1]

      (1) An, P.; Singh, B.; Singh, N. A review on coumarins as acetylcholinesterase inhibitors for zheimer's disease. Bioorganic & Medicinal Chemistry 2012, 20, 1175–1180.(1) An, P.; Singh, B.; Singh, N. A review on coumarins as acetylcholinesterase inhibitors for zheimer's disease. Bioorganic & Medicinal Chemistry 2012, 20, 1175–1180.

    2. [2]

      (2) Hu, Y. Q.; Zhang, J.; Chandrashankra, O.; Ip, F. C. F.; Ip, N. Y. Design, synthesis and evaluation of novel heterodimers of donepezil and huperzine fragments as acetylcholinesterase inhibitors. Bioorg. Med. Chem. 2013, 21, 676–683.(2) Hu, Y. Q.; Zhang, J.; Chandrashankra, O.; Ip, F. C. F.; Ip, N. Y. Design, synthesis and evaluation of novel heterodimers of donepezil and huperzine fragments as acetylcholinesterase inhibitors. Bioorg. Med. Chem. 2013, 21, 676–683.

    3. [3]

      (3) Shen, L. L.; Liu, G. X.; Tang, Y. Molecular docking and 3D-QSAR studies of 2-substituted 1-indanone derivatives as acetylcholinesterase inhibitors. Acta Pharmacol Sin. 2007, 28, 2053–2063.(3) Shen, L. L.; Liu, G. X.; Tang, Y. Molecular docking and 3D-QSAR studies of 2-substituted 1-indanone derivatives as acetylcholinesterase inhibitors. Acta Pharmacol Sin. 2007, 28, 2053–2063.

    4. [4]

      (4) Carlier, P. R.; Du, D. M.; Han, Y. F.; Liu, J.; Perola, E.; Williams, I. D.; Pang, Y. P. Dimerization of an inactive fragment of huperzine A produces a drug with twice the potency of the natural product. Angew. Chem., Int. Ed. 2000, 39, 1775–1777.(4) Carlier, P. R.; Du, D. M.; Han, Y. F.; Liu, J.; Perola, E.; Williams, I. D.; Pang, Y. P. Dimerization of an inactive fragment of huperzine A produces a drug with twice the potency of the natural product. Angew. Chem., Int. Ed. 2000, 39, 1775–1777.

    5. [5]

      (5) Carlier, P. R.; Du, D. M.; Han, Y. F.; Liu, J.; Perola, E.; Williams, I. D.; Pang, Y. P. Potent, easily synthesized huperzine A-tacrine hybrid acetylcholinesterase inhibitors. Bioorg. Med. Chem. Lett. 1999, 9, 2335–2338.(5) Carlier, P. R.; Du, D. M.; Han, Y. F.; Liu, J.; Perola, E.; Williams, I. D.; Pang, Y. P. Potent, easily synthesized huperzine A-tacrine hybrid acetylcholinesterase inhibitors. Bioorg. Med. Chem. Lett. 1999, 9, 2335–2338.

    6. [6]

      (6) Alonso, D.; Dorronsoro, I.; Rubio, L.; Muñz, P.; García-Palomero, E.; Del Monte, M.; Bidon-Chanal, A.; Orozco, M.; Luque, F. J.; Castro, A.; Medina, M.; Martínez, A. Donepezil-tacrine hybrid related derivatives as new dual binding site inhibitors of AChE. Bioorg. Med. Chem. 2005, 13, 6588–6597.(6) Alonso, D.; Dorronsoro, I.; Rubio, L.; Muñz, P.; García-Palomero, E.; Del Monte, M.; Bidon-Chanal, A.; Orozco, M.; Luque, F. J.; Castro, A.; Medina, M.; Martínez, A. Donepezil-tacrine hybrid related derivatives as new dual binding site inhibitors of AChE. Bioorg. Med. Chem. 2005, 13, 6588–6597.

    7. [7]

      (7) Shao, D.; Zou, C.; Luo, C.; Tang, X.; Li, Y. Synthesis and evaluation of tacrine-E2020 hybrids as acetylcholinesterase inhibitors for the treatment of Alzheimer's disease. Bioorg. Bioorg. Med. Chem. Lett. 2004, 14, 4639–4642.(7) Shao, D.; Zou, C.; Luo, C.; Tang, X.; Li, Y. Synthesis and evaluation of tacrine-E2020 hybrids as acetylcholinesterase inhibitors for the treatment of Alzheimer's disease. Bioorg. Bioorg. Med. Chem. Lett. 2004, 14, 4639–4642.

    8. [8]

      (8) Camps, P.; Formosa, X.; Galdeano, C.; Gomez, T.; Munoz-Torrero, D.; Scarpellini, M.; Viayna, E.; Badia, A.; Clos, M. V.; Camins, A.; Pallas, M.; Bartolini, M.; Mancini, F.; Andrisano, V.; Estelrich, J.; Lizondo, M.; Bidon-Chanal, A.; Luque, F. J. J. Med. Chem. 2008, 51, 3588–3598.(8) Camps, P.; Formosa, X.; Galdeano, C.; Gomez, T.; Munoz-Torrero, D.; Scarpellini, M.; Viayna, E.; Badia, A.; Clos, M. V.; Camins, A.; Pallas, M.; Bartolini, M.; Mancini, F.; Andrisano, V.; Estelrich, J.; Lizondo, M.; Bidon-Chanal, A.; Luque, F. J. J. Med. Chem. 2008, 51, 3588–3598.

    9. [9]

      (9) Tumiatti, V.; Minarini, A.; Bolognesi, M. L.; Milelli, A.; Rosini, M.; Melchiorre, C. Tacrine derivatives and Alzheimer's disease. Curr. Med. Chem. 2010, 17, 1825–1838.(9) Tumiatti, V.; Minarini, A.; Bolognesi, M. L.; Milelli, A.; Rosini, M.; Melchiorre, C. Tacrine derivatives and Alzheimer's disease. Curr. Med. Chem. 2010, 17, 1825–1838.

    10. [10]

      (10) Viayna, E.; Gomez, T.; Galdeano, C.; Ramirez, L.; Ratia, M.; Badia, A.; Clos, M. V.; Verdaguer, E.; Junyent, F.; Camins, A.; Pallas, M.; Bartolini, M.; Mancini, F.; Andrisano, V.; Arce, M. P.; Rodríguez-Franco, M. I.; Bidon-Chanal, A.; Luque, F. J.; Camps, P.; Munoz-Torrero, D. Novel huprine derivatives with inhibitory activity toward β-amyloid aggregation and formation as disease-modifying anti-alzheimer drug candidates. Chem. Med. Chem. 2010, 5, 1855–1870.(10) Viayna, E.; Gomez, T.; Galdeano, C.; Ramirez, L.; Ratia, M.; Badia, A.; Clos, M. V.; Verdaguer, E.; Junyent, F.; Camins, A.; Pallas, M.; Bartolini, M.; Mancini, F.; Andrisano, V.; Arce, M. P.; Rodríguez-Franco, M. I.; Bidon-Chanal, A.; Luque, F. J.; Camps, P.; Munoz-Torrero, D. Novel huprine derivatives with inhibitory activity toward β-amyloid aggregation and formation as disease-modifying anti-alzheimer drug candidates. Chem. Med. Chem. 2010, 5, 1855–1870.

    11. [11]

      (11) Monte-Millan, M.; Garcia-Palomero, E.; Valenzuela, R.; Usan, P.; de Austria, C.; Munoz-Ruiz, P.; Rubio, L.; Dorronsoro, I.; Martinez, A.; Medina, M. Dual binding site acetylcholinesterase inhibitors: potential new disease-modifying agents for AD. J. Mol. Neurosci. 2006, 30, 85–88.(11) Monte-Millan, M.; Garcia-Palomero, E.; Valenzuela, R.; Usan, P.; de Austria, C.; Munoz-Ruiz, P.; Rubio, L.; Dorronsoro, I.; Martinez, A.; Medina, M. Dual binding site acetylcholinesterase inhibitors: potential new disease-modifying agents for AD. J. Mol. Neurosci. 2006, 30, 85–88.

    12. [12]

      (12) Chitranshi, N.; Gupta, S.; Tripathi, P. K.; Seth, P. K. New molecular scaffolds for the design of Alzheimer's acetylcholinesterase inhibitors identified using ligand and receptor-based virtual screening. Med. Chem. Res. 2013, 22, 2328–2345.(12) Chitranshi, N.; Gupta, S.; Tripathi, P. K.; Seth, P. K. New molecular scaffolds for the design of Alzheimer's acetylcholinesterase inhibitors identified using ligand and receptor-based virtual screening. Med. Chem. Res. 2013, 22, 2328–2345.

    13. [13]

      (13) Kuntz, I. D. Structure-based strategies for drug design and discovery. Science 1992, 257, 1078–1082.(13) Kuntz, I. D. Structure-based strategies for drug design and discovery. Science 1992, 257, 1078–1082.

    14. [14]

      (14) Drews, J. Drug discovery: a historical perspective. Science 2000, 287, 1960–1964.(14) Drews, J. Drug discovery: a historical perspective. Science 2000, 287, 1960–1964.

    15. [15]

      (15) Deb, P. K.; Sharma, A.; Piplani, P.; Akkinepally, R. R. Molecular docking and receptor-specific 3D-QSAR studies of acetylcholinesterase inhibitors. Mol. Divers. 2012, 16, 803–823.(15) Deb, P. K.; Sharma, A.; Piplani, P.; Akkinepally, R. R. Molecular docking and receptor-specific 3D-QSAR studies of acetylcholinesterase inhibitors. Mol. Divers. 2012, 16, 803–823.

    16. [16]

      (16) Steiner, S.; Anderson, N. L. Pharmaceutical proteomics. AnnNY Acad Sci. 2000, 919, 48–51.(16) Steiner, S.; Anderson, N. L. Pharmaceutical proteomics. AnnNY Acad Sci. 2000, 919, 48–51.

    17. [17]

      (17) Graves, P. R.; Kwiek, J. J.; Fadden, P.; Ray, R.; Hardeman, K.; Coley, A. M.; Foley, M.; Haystead, T. A. Discovery of novel targets of quinoline drugs in the human purine binding proteome. Mol. Pharmacol. 2002, 62, 1364–1372.(17) Graves, P. R.; Kwiek, J. J.; Fadden, P.; Ray, R.; Hardeman, K.; Coley, A. M.; Foley, M.; Haystead, T. A. Discovery of novel targets of quinoline drugs in the human purine binding proteome. Mol. Pharmacol. 2002, 62, 1364–1372.

    18. [18]

      (18) Bruneau, J. M.; Maillet, J.; Tagat, E. Drug induced proteome changes in Candida albicans: comparison of the effect of beta (1, 3) glucan synthase inhibitors and two triazoles, fluconazole and itraconazole. Proteomics 2003, 3, 325–336.(18) Bruneau, J. M.; Maillet, J.; Tagat, E. Drug induced proteome changes in Candida albicans: comparison of the effect of beta (1, 3) glucan synthase inhibitors and two triazoles, fluconazole and itraconazole. Proteomics 2003, 3, 325–336.

    19. [19]

      (19) Cheung, J.; Rudolph, M. J.; Burshteyn, F.; Cassidy, M. S.; Gary, E. N.; Love, J.; Franklin, M. C.; Height, J. J. Structures of human acetylcholinesterasein complex with pharmacologically important ligands. J. Med. Chem. 2012, 55, 10282–10286.(19) Cheung, J.; Rudolph, M. J.; Burshteyn, F.; Cassidy, M. S.; Gary, E. N.; Love, J.; Franklin, M. C.; Height, J. J. Structures of human acetylcholinesterasein complex with pharmacologically important ligands. J. Med. Chem. 2012, 55, 10282–10286.

    20. [20]

      (20) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Mont Gomery, Jr. J. A.; Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03, Revision C. 02, Gaussian, Inc., Wallingford CT 2004.(20) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Mont Gomery, Jr. J. A.; Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03, Revision C. 02, Gaussian, Inc., Wallingford CT 2004.

    21. [21]

      (21) Kryger, G.; Silman, I.; Sussman, J. L. Three-dimensional structure of a complex of E2020 with acetylcholinesterase from Torpedo californica. J. Physiol. Paris 1998, 92, 191–194.(21) Kryger, G.; Silman, I.; Sussman, J. L. Three-dimensional structure of a complex of E2020 with acetylcholinesterase from Torpedo californica. J. Physiol. Paris 1998, 92, 191–194.

    22. [22]

      (22) Nachon, F.; Carletti, E.; Ronco, C.; Trovaslet, M.; Nicolet, Y.; Jean, L.; Renard, P. Y. Crystal structures of human cholinesterases in complex with huprine W and tacrine: elements of specificity for anti-Alzheimer's drugs targeting acetyl-and butyryl-cholinesterase. Biochem. J. 2013, 453, 393–399.(22) Nachon, F.; Carletti, E.; Ronco, C.; Trovaslet, M.; Nicolet, Y.; Jean, L.; Renard, P. Y. Crystal structures of human cholinesterases in complex with huprine W and tacrine: elements of specificity for anti-Alzheimer's drugs targeting acetyl-and butyryl-cholinesterase. Biochem. J. 2013, 453, 393–399.

    23. [23]

      (23) Carletti, E.; Colletier, J. P.; Dupeux, F.; Trovaslet, M.; Masson, P.; Nachon, F. Structural evidence that human acetylcholinesterase inhibited by tabun ages through O-dealkylation. J. Med. Chem. 2010, 53, 4002–4008.(23) Carletti, E.; Colletier, J. P.; Dupeux, F.; Trovaslet, M.; Masson, P.; Nachon, F. Structural evidence that human acetylcholinesterase inhibited by tabun ages through O-dealkylation. J. Med. Chem. 2010, 53, 4002–4008.

    24. [24]

      (24) Taylor, J. L.; Mayer, R. H.; Hime, C. M. Conformers of acetylcholinesterase: a mechanism of allosteric control. Mol. Pharmacol. 1994, 45, 74–83.(24) Taylor, J. L.; Mayer, R. H.; Hime, C. M. Conformers of acetylcholinesterase: a mechanism of allosteric control. Mol. Pharmacol. 1994, 45, 74–83.

    25. [25]

      (25) Pang, Y. P.; Quiram, P.; Jalacie, T.; Hong, F.; Brimijoin, S. Highly potent, selective, and low cost bis-tetrahydroaminacrine inhibitors of acetylcholinesterase. Steps toward novel drugs for treating Alzheimer's disease. J. Biol. Chem. 1996, 271, 23646–23649.(25) Pang, Y. P.; Quiram, P.; Jalacie, T.; Hong, F.; Brimijoin, S. Highly potent, selective, and low cost bis-tetrahydroaminacrine inhibitors of acetylcholinesterase. Steps toward novel drugs for treating Alzheimer's disease. J. Biol. Chem. 1996, 271, 23646–23649.

    26. [26]

      (26) Bolognes, M. L.; Banzi, R.; Bartolini, M.; Cavall, A.; Tarozzi, A.; Andrisano, V.; Minarini, A.; Rosini, M.; Tumiatti, V.; Bergamini, C.; Fato, R.; Lenaz, G.; Hrelia, P.; Cattaneo, A.; Recanatini, M.; Melchiorre, C. Novel class of quinone-bearing polyamines as multi-target-directed ligands to combat Alzheimer's disease. J. Med. Chem. 2007, 50, 4882–4897.(26) Bolognes, M. L.; Banzi, R.; Bartolini, M.; Cavall, A.; Tarozzi, A.; Andrisano, V.; Minarini, A.; Rosini, M.; Tumiatti, V.; Bergamini, C.; Fato, R.; Lenaz, G.; Hrelia, P.; Cattaneo, A.; Recanatini, M.; Melchiorre, C. Novel class of quinone-bearing polyamines as multi-target-directed ligands to combat Alzheimer's disease. J. Med. Chem. 2007, 50, 4882–4897.

    27. [27]

      (27) Bolognesi, M. L.; Bartolini, M.; Mancin, F.; Chiriano, G.; Ceccarini, L.; Rosini, M.; Milelli, A.; Tumiatti, V.; Andrisano, V.; Melchiorre, C. Bis(7)-tacrine derivatives as multitarget-directed ligands: focus on anticholinesterase and antiamyloid activities. Chem. Med. Chem. 2010, 5, 1215–1220.(27) Bolognesi, M. L.; Bartolini, M.; Mancin, F.; Chiriano, G.; Ceccarini, L.; Rosini, M.; Milelli, A.; Tumiatti, V.; Andrisano, V.; Melchiorre, C. Bis(7)-tacrine derivatives as multitarget-directed ligands: focus on anticholinesterase and antiamyloid activities. Chem. Med. Chem. 2010, 5, 1215–1220.

    28. [28]

      (28) Kryger, G.; Silman, I.; Sussman, J. L. Structure of acetylcholinesterase complexed with E2020 (Aricept): implications for the design of new anti-Alzheimer drugs. Structure 1999, 7, 297–307.(28) Kryger, G.; Silman, I.; Sussman, J. L. Structure of acetylcholinesterase complexed with E2020 (Aricept): implications for the design of new anti-Alzheimer drugs. Structure 1999, 7, 297–307.

    29. [29]

      (29) Volkov, A.; King, H. F.; Coppens, P.; Farrugia, L. On the calculation of the electrostatic potential, electric field and electric field gradient from the aspherical pseudoatom model. Acta Crystallogr. A 2006, 62, 400–408.(29) Volkov, A.; King, H. F.; Coppens, P.; Farrugia, L. On the calculation of the electrostatic potential, electric field and electric field gradient from the aspherical pseudoatom model. Acta Crystallogr. A 2006, 62, 400–408.

    30. [30]

      (30) Luger, P.; Hübschle, C. B. MolIso–a program for colour-mapped iso-surfaces. J. Appl. Crystallogr. 2006, 39, 901–904.(30) Luger, P.; Hübschle, C. B. MolIso–a program for colour-mapped iso-surfaces. J. Appl. Crystallogr. 2006, 39, 901–904.

    31. [31]

      (31) Luger, P.; Weber, M.; Dittrich, B. Electron density study of the anti-Alzheimer's disease drug donepezil from conventionalx-ray data and invariom database application. Future Med. Chem. 2012, 4, 1399–1407.(31) Luger, P.; Weber, M.; Dittrich, B. Electron density study of the anti-Alzheimer's disease drug donepezil from conventionalx-ray data and invariom database application. Future Med. Chem. 2012, 4, 1399–1407.

    32. [32]

      (32) Chen, J. W.; Luo, Y. L.; Hwang, M. J.; Peng, F. C.; Ling, K. H. A tremorgenic mycotoxin that inhibits acetylcholinesterase with a noncovalent yet irreversible binding mechanism. J. Biol. Chem. 1999, 274, 34916–34923.(32) Chen, J. W.; Luo, Y. L.; Hwang, M. J.; Peng, F. C.; Ling, K. H. A tremorgenic mycotoxin that inhibits acetylcholinesterase with a noncovalent yet irreversible binding mechanism. J. Biol. Chem. 1999, 274, 34916–34923.

    33. [33]

      (33) Ling, K. H.; Chiou, C. M.; Tseng, Y. L. Biotransformation of territrems by S9 fraction from rat liver. Drug Metab. Dispos. 1991, 19, 587–595.(33) Ling, K. H.; Chiou, C. M.; Tseng, Y. L. Biotransformation of territrems by S9 fraction from rat liver. Drug Metab. Dispos. 1991, 19, 587–595.

    34. [34]

      (34) Wu, W. J.; Lai, R.; Zheng, K. C.; Yun, F. C. Quantitative structure-activity relationship of indolo[1,2-b] quinazoline derivatives with antitumor activity. Acta Phys.-Chim. Sin. 2005, 21, 28–32.(34) Wu, W. J.; Lai, R.; Zheng, K. C.; Yun, F. C. Quantitative structure-activity relationship of indolo[1,2-b] quinazoline derivatives with antitumor activity. Acta Phys.-Chim. Sin. 2005, 21, 28–32.

    35. [35]

      (35) Wang, X. W.; Jiang, G.; Du, J. G. Structures, infrared spectra and reactivities of (+)-catechin metal complexes. Acta Phys. Chim. Sin. 2011, 27, 309–314.(35) Wang, X. W.; Jiang, G.; Du, J. G. Structures, infrared spectra and reactivities of (+)-catechin metal complexes. Acta Phys. Chim. Sin. 2011, 27, 309–314.

    36. [36]

      (36) Feng, C. J. Theoretical studies on quantitative structure-activity relationship and structural modification for 3-substituted sulfur-5-(2-hydroxyphenyl)-4H-1,2,4-triazole compounds. Acta Chimica Sinica 2012, 4, 512–518.(36) Feng, C. J. Theoretical studies on quantitative structure-activity relationship and structural modification for 3-substituted sulfur-5-(2-hydroxyphenyl)-4H-1,2,4-triazole compounds. Acta Chimica Sinica 2012, 4, 512–518.

    37. [37]

      (37) Zhang, J.; Shen, P.; Lu, T.; Yu, D. N.; Li, H.; Yang, G. Z. Theoretical studies on quantitative structure-activity relationship and structural modification for the inhibition of MMP-9 by flavonoids. Acta Chimica Sinica 2011, 4, 383–392.(37) Zhang, J.; Shen, P.; Lu, T.; Yu, D. N.; Li, H.; Yang, G. Z. Theoretical studies on quantitative structure-activity relationship and structural modification for the inhibition of MMP-9 by flavonoids. Acta Chimica Sinica 2011, 4, 383–392.

    38. [38]

      (38) Aihara, J. I. Weighted HOMO LUMO energy separation as an index of kinetic stability for fullerenes. Theor. Chem. Acc. 1999, 102, 134-138.(38) Aihara, J. I. Weighted HOMO LUMO energy separation as an index of kinetic stability for fullerenes. Theor. Chem. Acc. 1999, 102, 134-138.

    39. [39]

      (39) Clark, R. D.; Strizhev, A.; Leonard, J. M.; Blake, J. F.; Matthew, J. B. Consensus scoring for ligand/protein interactions. J. Mol. Graphics. Modell. 2002, 20, 281–295.(39) Clark, R. D.; Strizhev, A.; Leonard, J. M.; Blake, J. F.; Matthew, J. B. Consensus scoring for ligand/protein interactions. J. Mol. Graphics. Modell. 2002, 20, 281–295.

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