In silico pharmacophore model for tabun-inhibited acetylcholinesterase reactivators: A study of their stereoelectronic properties

Chemical Research in Toxicology

Volumn 23, Issue 1, 2010, Pages 26-36

  Bhattacharjee, Apurba K ^a   Kuča, Kamil ^b   Musilek, Kamil ^b   Gordon, Richard K ^a  

^a WALTER REED ARMY INSTITUTE OF RESEARCH   (United States)

^b UNIVERSITY OF DEFENCE   (Czech Republic)

Author keywords

[No Author keywords available]

Indexed keywords

CHOLINESTERASE REACTIVATOR; NITROGEN; OXIME DERIVATIVE; PYRIDINIUM DERIVATIVE; TABUN;

ANALYSIS; ARTICLE; BINDING AFFINITY; CHEMICAL STRUCTURE; COMPUTER MODEL; HUMAN; HYDROPHILICITY; INTOXICATION; METHODOLOGY; PHARMACOPHORE; QUANTUM CHEMISTRY; STEREOCHEMISTRY; STRUCTURE ACTIVITY RELATION; SURFACE PROPERTY;

ACETYLCHOLINESTERASE; BINDING SITES; CHEMICAL WARFARE AGENTS; CHOLINESTERASE INHIBITORS; CHOLINESTERASE REACTIVATORS; DRUG DESIGN; MODELS, CHEMICAL; OXIMES; PHOSPHORIC ACID ESTERS; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP; QUANTUM THEORY; STEREOISOMERISM;

EID: 75149174377     PISSN: 0893228X     EISSN: 15205010     Source Type: Journal    
DOI: 10.1021/tx900192u     Document Type: Article

References (41)

1. Marrs, T. C. (1993) Organophosphate poisoning. Pharmacol. Ther. 58, 51-66.
2. Bakshi, K. S., Pang, S. N. J., and Snyder, R. (2000) Review of the US Army's health risk assessment for oral exposure to six chemical-warfare agents - Introduction to the special issue. J. Toxicol. Environ. Health A 59, 282-283.
3. Sussaman, J. L., Harel, M., Frolow, F., Oefner, C., Goldman, A., Toker, L., and Silman, I. (1991) Atomic structure of acetylcholinesterase from torpedo californica: A prototypic acetylcholine-binding protein. Science 253, 872-879.
4. Barak, D., Kronman, C., Ordentlich, A., Ariel, N., Bromberg, A., Marcus, D., Lazar, A., Velan, B., and Shafferman, A. (1994) Acetylcholinesterase peripheral anionic site degeneracy conferred by amino acid arrays sharing a common core. J. Biol. Chem. 269, 6296-6305.
5. Ekstrom, F., Akfur, C., Tunemalm, A. K., and Lundberg, S. (2006) Structural changes of phenylalanine 338 and histidine 447 revealed by the crystal structures of tabun inhibited murine acetylcholinesterase. Biochemistry 45, 74-81.
6. Ekstrom, F., Pang, Y. P., Boman, M., Artursson, E., Akfur, C., and Borjegren, S. (2006) Crystal structures of acetylcholinesterase in complex with HI-6, ortho-7 and obidoxime: Structural basis for differences in the ability to reactivate tabun conjugates. Biochem. Pharmacol. 72, 597-607.
7. Bajgar, J. (2004) Organophosphates/nerve agent poisoning: mechanism of action, diagnosis, prophylaxis, and treatment. Adv. Clin. Chem. 38, 151-216.
8. (a) Ekstrom, F. J., Astot, C., and Pang, Y. P. (2007) Novel nerve-agent antidote design based on crystallographic and mass spectrometric analyses of tabun-conjugated acetylcholinesterase in complex with antidotes. Clin. Pharmacol. Ther. 82, 282-293.
9. (b) Ekstrom, F. J., Hornberg, A., Artursson, E., Hammarstrom, L. G., Schneider, G., and Pang, Y. P. (2009) Structure of HI-6. Sarin- Acetylcholinesterase determined by x-ray crystallography and molecular dynamics simulation: Reactivator mechanism and design. PLoS ONE 4, e5957.
10. Kassa, J., Kuca, K., and Cabal, J. (2005) A comparison of the potency of trimedoxime and other currently available oximes to reactivate tabun-inhibited acetylcholinesterase and eliminate acute toxic effects of tabun. Biomed. Pap. 149 (2), 419-423.
11. Musilek, K., Kuca, K., Jun, D., and Dolezal, M. (2007) Progress in synthesis of new acetylcholinesterase reactivators during the period 1990-2004. Curr. Org. Chem. 11 (2), 229-238.
12. Jokanovic, M., and Stojiljkovic, M. P. (2006) Current understanding of the application of pyridinium oximes as cholinesterase reactivators in treatment of organophophate posoning. Eur. J. Pharmacol. 553, 10-17.
13. Kuca, K., Cabal, J., Kassa, J., Jun, D., and Hrabinova, M. (2005) A comparison of the potency of the oxime HLö-7 and currently used oximes (HI-6, pralidoxime, obidoxime) to reactivate nerve agent-inhibited rat brain acetylcholinesterase by in vitro methods. Acta Med. (Hradec Kralove) 48 (2), 81-86.
14. Musilek, K., Jun, D., Cabal, J., Kassa, J., Gunn-Moore, F., and Kuca, K. (2007) Design of a potent reactivator of tabun-inhibited acetylcholinesterase - Synthesis and evaluation of (E)-1-(4-carbamoylpyridinium)-4-(4- hydroxyiminomethylpyridinium)-but-2-ene dibromide (K203). J. Med. Chem. 50 (22), 5514-5518.
15. Kassa, J., Kuca, K., Bartosova, L., and Kunesova, G. (2007) The development of new structural analogues of oximes for the antidotal treatment of poisoning by nerve agents and the comparison of their reactivating and therapeutic efficacy with currently available oximes. Curr. Org. Chem. 11, 267-283.
16. Karelson, M., Lobanov, V. S., and Katritzky, A. R. (1996) Quantum-chemical descriptors in QSAR/QSPR studies. Chem. Rev. 96, 1027-1044, and references cited therein.
17. Tomasi, J., Alagona, G., Bonaccorsi, R., Ghio, C., and Canni, R. (1991) Theoretical Models of Chemical Bonding (Maksic, Z., Eds.) Part 4, Springer, Berlin.
18. Murray, J. S., Zilles, B. A., Jayasuriya, K., and Politzer, P. (1986) Comparative analysis of the electrostatic potentials of dibenzofuran and some dibenzo-p-dioxins. J. Am. Chem. Soc. 108, 915-918.
19. Gund, P. (2000) Evolution of the pharmacophore concept in pharmaceutical research. In Pharmacophore Perception, Development and Use in Drug Design (Güner, O. F., Ed.) pp 5-11, International University Line, La Jolla, CA.
20. Bhattacharjee, A. K., Geyer, J. A., Woodard, C. L., Kathcart, A. K., Nichols, D. A., Prigge, S. T., Li, Z., Mott, B. T., and Waters, N. C. (2004) A three dimensional in silico pharmacophore model for inhibition of Plasmodium falciparum cyclin dependent kinases and discovery of different classes of novel pfmrk specific inhibitors. J. Med. Chem. 47, 5418-5426.
21. Bhattacharjee, A. K. (2007) Virtual screening of compound libraries using in silico three dimensional pharmacophores to aid the discovery and design of antimalarial and antileishmanial agents. Front. Drug Des. Discovery 3, 257-292.
22. SPARTAN version 5.1, Wavefunction, Inc., 18401 Von Karman Ave., #370, Irvine, CA 92715.
23. Dewar, M. J. S., Zoebisch, E. G., Horsley, E. F., and Stewart, J. J. P. (1985) A new general purpose quantum mechanical molecular model. J. Am. Chem. Soc. 107, 3902-3909.
24. Frisch, M. J., Trucks, G. W., Schlegel, H. B., Scuseria, G. E., Robb, M. A., Cheeseman, J. R., Zakrzewski, V. G., Montgomery, J. A., Stratmann, R. E., Burant, S., Dapprich, J. C., Millam, J. M., Daniels, A. D., Kudin, K. N., Strain, M. C., Farkas, O., Tomasi, J., Barone, V., Cossi, M., Cammi, R., Mennucci, B., Pomelli, C., Adamo, C., Clifford, S., Ochterski, J., Petersson, G. A., Ayala, P. Y., Cui, Q., Morokuma, K., Malick, D. K., Rabuck, A. D., Raghavachari, K., Foresman, J. B., Cioslowski, J., Ortiz, J. V., Stefanov, B. B., Liu, G., Liashenko, A., Piskorz, P., Komaromi, I., Gomperts, R., Martin, R. L., Fox, D. J., Keith, T., Al-Laham, M. A., Peng, C. Y., Nanayakkara, A., Gonzalez, C., Challacombe, M., Gill, P. M. W., Johnson, B. G., Chen, W., Wong, M. W., Andres, J. L., Head-Gordon, M., Replogle, E. S., and Pople, J. A. (1998) Gaussian 98, Revision A.1, Gaussian, Inc., Pittsburgh, PA.
25. Mecozzi, S., West, A. P., and Dougherty, D. A. (1996) Cation-pi interactions in simple aromatics: electrostatic provide a predictive model. J. Am. Chem. Soc. 118, 2307-2308.
26. Dixon, R. W., Leonard, J. M., and Hehre, W. J. A. (1993) Continuum solvation model for the AM1 semi-empirical method. Israel J. Chem. 33, 427-434.
27. Tomasi, J., Cammi, R., and Mennucci, B. (1999) Medium effects on the properties of chemical systems: An overview of recent reformulations in the polarizable continuum model (PCM). Int. J. Quantum Chem. 75, 767.
28. CATALYST version 4.10, Accelrys Inc., San Diego, CA.
29. Kuca, K., Jun, D., Kim, T. H., Cabal, J., and Jung, Y. S. (2006) In vitro evaluation of new acetylcholinesterase reactivators as casual antidotes against tabun and cyclosarin. Bull. Korean Chem. Soc. 27, 395-398.
30. Greenidge, P. A., and Weiser, J. (2001) A comparison of methods for pharmacophore generation with the catalyst software and their use for 3D-QSAR: Application to a set of 4-aminopyridine thrombin inhibitors. Mini Rev. Med. Chem. 1, 79-87.
31. Kuca, K., Jun, D., and Musilek, K. (2006) Structural requirements of acetylcholinesterase reactivators. Mini Rev. Med. Chem. 6 (3), 269-277.
32. Kassa, J., Karasova, J., Musilek, K., and Kuca, K. (2008) An evaluation of therapeutic and reactivating effects of newly developed oximes (K156, K203) and commonly used oximes (obidoxime, trimedoxime, HI-6) in tabun-poisoned rats and mice. Toxicology 243, 311-316.
33. Bartosova, L., Kuca, K., Kunesova, G., and Jun, D. (2006) The acute toxicity of acetylcholinesterase reactivators in mice in relation to their structure. Neurotoxic. Res. 9 (4), 291-296.
34. TOPKAT 6.1, Accelrys Inc., San Diego, CA.
35. Lundy, P. M., Raveh, L., and Amitai, G. (2006) Development of the bisquaternary oxime HI-6 toward clinical use in the treatment of organophosphate nerve agent poisoning. Toxicol. Rev. 25, 231-43.
36. Kassa, J., Kuca, K., and Cabal, J. (2005) A comparison of the efficacy of currently available oximes against tabun in rats. Biologia 60 (17), 77-79.
37. Bajgar, J., Fusek, J., Kuca, K., Bartosova, L., and Jun, D. (2007) Treatment of organophosphate intoxication using cholinesterase reactivators: facts and fiction. Mini Rev. Med. Chem. 7 (5), 461-466.
38. Bhattacharjee, A. K., and Karle, J. M. (1999) Stereoelectronic properties of antimalarial artemisinin analogues in relation to neurotoxicity. Chem. Res. Toxicol. 12, 422-428.
39. Kuca, K., Patočka, J., Cabal, J., and Jun, J. (2004) Reactivation of organophosphate-inhibited acetylcholinesterase by quaternary pyridinium aldoximes. Neurotoxic. Res. 6 (7-8), 565-570.
40. Wang, Q., and Pang, Y. P. (2007) Normal-mode-analysis-monitored energy minimization procedure for generating small-molecule bound conformations. PLoS 2 (10), e1025.
41. Wang, Q., and Pang, Y. P. (2007) Preference of small molecules for local minimum conformations when binding to proteins. PLoS 2 (9), e820.