多种类杂环化合物的药理和毒理活性系数构效关系

doi:10.3866/PKU.WHXB201404161

Abstract

Abstract:

Heterocyclic molecules play a crucial role in health care and in pharmaceutical drug design. A large number of drugs used in Western medical practice are heterocyclic molecules. In this study, a set of norm indexes of the extended distance matrix are proposed. From these a stable and accurate structureproperty relationship model was developed for the prediction of the aryl hydrocarbon receptor binding affinity (pEC₅₀) of dibenzofurans and the mutagenic potency (lnR) of aromatic and heteroaromatic amines. Our results indicate that the new model, based on these norm indexes, provides very satisfactory results, and that the average absolute differences for pEC₅₀ prediction and lnR prediction were 0.403 and 0.702 with r² (square correlation coefficient) values of 0.876 and 0.779, respectively. A comparison of these results with other methods demonstrates that our method, based only on the same mathematical model, performed better in terms of both accuracy and stability.

Key words: Dibenzofuran, Aromatic and heteroaromatic amine, Aryl hydrocarbon receptor affinity, Mutagenic potency, Structure-property relationship, Norm index, Prediction

MSC2000:

O641

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ZHU Zhi-Chen, WANG Qiang, JIA Qing-Zhu, XIA Shu-Qian, MA Pei-Sheng. Structure-Property Relationship for the Pharmacological and Toxicological Activity of Heterocyclic Compounds[J].Acta Phys. -Chim. Sin., 2014, 30(6): 1086-1090.

References

(1) Hammond, G. S. Norris Award Lecture, 1968.
(2) Michielan, L.; Moro, S. J. Chem. Inf. Model. 2010, 50, 961. doi: 10.1021/ci100072z
(3) Khan, M. T.; Sylte, I. Curr. Drug Discovery Technol. 2007, 4, 141. doi: 10.2174/157016307782109706
(4) Mager, D. E. Adv. Drug Delivery Rev. 2006, 58, 1326. doi: 10.1016/j.addr.2006.08.002
(5) Zhu, H.; Tropsha, A.; Fourches, D.; Varnek, A.; Papa, E.; Gramatica, P.; Oberg, T.; Dao, P.; Cherkasov, A.; Tetko, I. V. J. Chem. Inf. Model. 2008, 48, 766. doi: 10.1021/ci700443v
(6) Basak, S. C.; Mills, D. SAR QSAR Environ. Res. 2001, 12, 481. doi: 10.1080/10629360108039830
(7) Gute, B. D.; Balasubramanian, K.; Geiss, K. T.; Basak, S. C. Environ Toxicol Pharmacol, 2004, 16, 121.
(8) Restrepo, G.; Basak, S. C.; Mills, D. Curr. Comput. Aided Drug Des. 2011, 7, 109. doi: 10.2174/157340911795677639
(9) Basak, S. C.; Mills, D. R.; Balaban, A. T.; Gute, B. D. J. Chem. Inf. Comput. Sci. 2001, 41, 671. doi: 10.1021/ci000126f
(10) Godavarthy, S. S.; Robinson, R. L., Jr.; Gasem, K. A. M. Fluid Phase Equilib. 2008, 264, 122. doi: 10.1016/j.fluid.2007.11.003
(11) Basak, S. C.; Mills, D.; Gute, B. D.; Natarajan, R. Top Heterocycl. Chem. 2006, 3, 39.
(12) Li, X. L.; Ye, L.;Wang, X. X.;Wang, X. Z.; Liu, H. L.; Qian, X. P.; Zhu, Y. L.; Yu, H. X. Sci. Total Environ. 2012, 441, 230. doi: 10.1016/j.scitotenv.2012.08.072
(13) Doering, J. A.;Wiseman, S.; Beitel, S. C.; Giesy, J. P.; Hecker, M. Aquat. Toxicol. 2014, 150, 27. doi: 10.1016/j.aquatox.2014.02.009
(14) Gu, C.; Goodarzi, M.; Yang, X.; Bian, Y.; Sun, C.; Jiang, X. Toxicol. Lett. 2012, 208, 269.
(15) Hankinson, O. Arch. Biochem. Biophys. 2005, 433, 379. doi: 10.1016/j.abb.2004.09.031
(16) Basak, S. C.; Mills, D.; Mumtaz, M. M.; Balasubramanian, K. Indian J. Chem. 2003, 42A, 1385.
(17) Basak, S. C.; Mills, D.; Gute, B. D.; Hawkins, D. M. Predicting Mutagenicity of Congeneric and DiverseSets of Chemicals Using Computed Molecular Descriptors: a Hierarchical Approach. In Benigni R(ed) Quantitative Structure -Activity Relationship (QSAR) Models of Mutagens and Carcinogens; CRC: Boca Raton, FL, 2003; pp 207-208.
(18) Cao, F.; Li, X.; Ye, L.; Xie, Y.;Wang, X.; Shi,W.; Qian, X.; Zhu, Y.; Yu, H. Environ. Toxicol. Pharmacol. 2013, 36, 626. doi: 10.1016/j.etap.2013.06.004
(19) Wang, Q.; Ma, P. S.; Jia, Q. Z.; Xia, S. Q. J. Chem. Eng. Data 2008, 53, 1103. doi: 10.1021/je700641j
(20) Wang, Q.; Jia, Q. Z.; Ma, P. S. J. Chem. Eng. Data 2012, 57, 169. doi: 10.1021/je200971z
(21) Jia, Q. Z.;Wang, Q.; Ma, P. S.; Xia, S. Q.; Yan, F. Y.; Tang, H. M. J. Chem. Eng. Data 2012, 57, 3357. doi: 10.1021/je301070f
(22) Zhu, Z. C.;Wang, Q.; Jia, Q. Z.; Tang, H. M.; Ma, P. S. Acta Phys. -Chim. Sin. 2013, 29 (1), 30. [朱志臣, 王强, 贾青竹, 汤红梅, 马沛生. 物理化学学报, 2013, 29 (1), 30.] doi: 10.3866/PKU.WHXB201210265
(23) Yan, F.; Xia, S.;Wang, Q.; Ma, P. S. J. Chem. Eng. Data 2012, 57, 805. doi: 10.1021/je201023a
(24) Yan, F.; Xia, S.;Wang, Q.; Ma, P. S. J. Chem. Eng. Data 2012, 57, 2252. doi: 10.1021/je3002046
(25) Wang, Q.; Jia, Q. Z.; Yan, L. H.; Ma, P. S.; Xia, S. Q. doi: 10.1016/j.chemosphere.2014.02.030
(26) So, S. S.; Karplus, M. J. Med. Chem. 1997, 40, 4360.
(27) Debnath, A. K.; Debnath, G.; Shusterman, A. J.; Hansch, C. A. Environ. Mol. Mutagen. 1992, 19, 37. doi: 10.1002/em.2850190107

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Structure-Property Relationship for the Pharmacological and Toxicological Activity of Heterocyclic Compounds

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