Citation: Li-Lan ZHU, Zheng-Long QIN, Chang-Jun FENG. CoMFA Model and Molecular Design of Anti-excitatory Activity for Benzodiazepinooxazole Derivatives against Mice[J]. Chinese Journal of Structural Chemistry, ;2021, 40(8): 1075-1081. doi: 10.14102/j.cnki.0254–5861.2011–3164 shu

CoMFA Model and Molecular Design of Anti-excitatory Activity for Benzodiazepinooxazole Derivatives against Mice

a.
Department of Physical Education, Guangdong Industry Polytechnic, Guangzhou 510300, China
b.
College of Chemistry and Materials Science, Jiangsu Normal University, Xuzhou 21116, China
c.
School of Chemistry & Chemical Engineering, Xuzhou University of Technology, Xuzhou 221018, China

Corresponding author: Chang-Jun FENG, fengcj@xzit.edu.cn
Received Date: 1 March 2021
Accepted Date: 25 April 2021

Fund Project: the National Natural Science Foundation of China 21075138special fund of State Key Laboratory of Structure Chemistry 2016028Natural Science Foundation of Guangdong Industry Polytechnic KJ2019-032

Figures(4)

A 3D-QSAR study was conducted to analyze the anti-excitatory activity (pE) of benzodiazepinooxazole derivatives to mice by the comparative molecular field analysis (CoMFA) method. Among the 54 active molecules, a training set of 46 compounds was randomly selected to construct the CoMFA model; the remaining compounds, together with template molecule (No. 54) and two newly designed molecules constitute a test set of 17 compounds to validate the model. The obtained cross-validation coefficient (R_cv²), the non-cross validation coefficient (R²), and the test value F of the CoMFA model for training set are 0.516, 0.899, and 57.57, respectively. The model was used to predict the activities of all compounds in the training and testing sets, and the results indicated that the model had good correlation, strong stability and good predictability. Based on the 3D contour maps, eight novel benzodiazepinooxazole derivatives with higher anti-excitatory activity were designed. However, the effectiveness of these novel benzodiazepinooxazole derivatives is still needed to be verified by the experimental results.
- benzodiazepinooxazole derivative,
- mice,
- anti-excitatory activity,
- 3D-QSAR,
- comparative molecular field analysis
1. [1]
  Zhu, L. L. QSAR model for prediction of the aroma intensities of volatile compounds in Chinese rice wine. Food Sci. 2013, 34, 138–141.
2. [2]
  Feng, H.; Feng, C. J. 3D-QSAR studies on the anti-tumor activity of N-aryl-salicylamide derivatives. Chin. J. Struct. Chem. 2019, 39, 1874–1880.
3. [3]
  Feng, H.; Du, X. H.; Chen, Y.; Feng, C. J. 3D-QSAR models of anti-tumor activity for histone deacetylase inhibitors containing dihydropyridin-2-one. Chin. J. Struct. Chem. 2020, 39, 855–862.
4. [4]
  Zhu, L. L. Study on the relative activity for thiazide diuretics in doping based on artificial neural network. J. Guangdong Ind. Polytechnic 2019, 18, 7–10.
5. [5]
  Zheng, S. S.; Li, T. T.; Wang, J.; Hu, Y. J.; Zhang, H. X.; Zhao, S. X.; Zhao, Y. H.; Li, C. QSAR models for predicting the aqueous reaction rate constants of aromatic compounds with hydrated electrons. Envir. Chem. 2019, 38, 1005–1013.
6. [6]
  Qu, R. J.; Liu, H. X.; Feng, M. B.; Yang, X.; Wang, Z. Y. Investigation on intramolecular hydrogen bond and some thermodynamic properties of polyhydroxylated anthraquinones. J. Chem. Eng. Data 2012, 57, 2442–2455. doi: 10.1021/je300407g
7. [7]
  Yang, F.; Wang, M.; Wang, Z. Y. Sorption behavior of 17 phthalic acid esters on three soils: effects of pH and dissolved organic matter, sorption coefficient measurement and QSPR study. Chemosphere 2013, 93, 82–89. doi: 10.1016/j.chemosphere.2013.04.081
8. [8]
  Feng, C. J. QSAR studies on the biological activity of substituted triazolo-benzothiazole derivatives. J. Xuzhou Inst. Tech. (Nat. Sci. Ed. ) 2018, 33, 39–44.
9. [9]
  Qu, R. J.; Liu, J. Q.; Li, C. G.; Wang, L. S.; Wang, Z. Y.; Wu J. C. Experimental and theoretical insights into the photochemical decomposition of environmentally persistent perfluorocarboxylic acids. Water Research 2016, 104, 34–43. doi: 10.1016/j.watres.2016.07.071
10. [10]
  Zeng, X. L.; Qu, R. J.; Feng, M. B.; Jing, C.; Wang, L. S; Wang, Z. Y. Photodegradation of polyfluorinated dibenzo-p-dioxins (PFDDs) in organic solvents: experimental and theoretical studies. Environ. Sci. Techn. 2016, 50, 8128–8134. doi: 10.1021/acs.est.6b02682
11. [11]
  Tong, J. B.; Qin, S. S.; Lei, S.; Wang, Y. A 3D-QSAR study of HIV-1 integrase inhibitors using RASMS and Topomer CoMFA. Chin. J. Struct. Chem. 2019, 38, 867–881.
12. [12]
  Feng, C. J. CoMFA model of inhibitory activity for nitrobenzene derivatives to photobacteria. J. Xuzhou Inst. Tech. (Nat. Sci. Ed. ) 2020, 35, 28–31.
13. [13]
  Shu, M.; Wu, T.; Wang, B. W.; Li, J.; Xu, C. M.; Lin, Z. H. 3D-QSAR and surflex docking studies of a series of alkaline phosphatase inhibitors. Chin. J. Struct. Chem. 2019, 38, 7–16.
14. [14]
  An, C. H.; Shu, M.; Zai, X. L.; Zhang, B. N.; Li, J.; Chang, Z. C.; Hu, Y.; Lin, Z. H. Combined 3D-QSAR, pharmacophore and docking studies on benzene-sulfonamide derivatives as potent 12-lipoxygenase inhibitors. Lett. Drug. Des. Discov. 2017, 14, 74–82.
15. [15]
  Tong, J. B.; Zhan, P.; Bai, M.; Yao, T. Molecular modeling studies of human immunodeficiency virus type 1 protease inhibitors using three-dimensional quantitative structure-activity relationship, virtual screening, and docking simulations. J. Chemometrics 2016, 30, 523–536.
16. [16]
  Liu, H. X.; Shi, J. Q.; Liu, H.; Wang, Z. Y. Improved 3D-QSPR analysis of the predictive octanoleair partition coefficients of hydroxylated and methoxylated polybrominated diphenyl ethers. Atmos. Environ. 2013, 77, 840–845. doi: 10.1016/j.atmosenv.2013.05.068
17. [17]
  Wu, B. J.; Gu, P.; Wang, M. W.; Zhang, Y. M.; Yang, J. Changes in the levels of glucocorticoid and its receptors in rats with epilepsy induced in 3-ethyl-3-methyl glutarimide. Chin. J. Clin. Rehab. 2004, 8, 4496–4497.
18. [18]
  Toshiharu, K.; Isao, N.; Seigo, A.; Hiromu, T. Effects of oxazolam, cloxazolam, and CS-386, new anti-anxiety drugs, on socially induced suppression and aggression in pairs of monkeys. Psychopharmacology 1977, 52, 17–23 doi: 10.1007/BF00426594
19. [19]
  William, A. B. Enantioselective autocatalysis. II. Racemization studies on a 1, 4-benzodiazepinooxazole derivative. Orig. Life Evol. Biosph. 1995, 25, 401–414. doi: 10.1007/BF01581778
20. [20]
  William, A. B. Enantioselective autocatalysis. IV. Implications for parity violation effects. Orig. Life Evol. Biosph. 1996, 26, 27–45. doi: 10.1007/BF01808158
21. [21]
  Yoshimoto, M.; Kamioka, T.; Miyadera, T.; Kobayashi, S.; Takagi, H.; Tachikawa, R. Quantitative structure-activity correlation researchships in minor tranquilizers benzodiazepinooxazole derivatives. Chem. Pharm. Bull. 1977, 25, 1378–1390. doi: 10.1248/cpb.25.1378
22. [22]
  Feng, C. J. CoMFA model of herbicidal activity of phenyl-sulfonylured derivatives. J. Xuzhou Inst. Tech. (Nat. Sci. Ed. ) 2019, 34, 21–25.
23. [23]
  Joshi, S. D.; More, U. A.; Aminabhavi, T. M.; Badiger, A. M. Two- and three-dimensional QSAR studies on a set of antimycobacterial pyrroles: CoMFA, Topomer CoMFA, and HQSAR. Med. Chem. Res. 2014, 23, 107–126.
24. [24]
  Cramer, R. D.; Patterson, D. E.; Bunce, J. D. Comparative molecular field analysis (CoMFA). 1. effect of shape on binding of steroids to carrier proteins. J. Am. Chem. Soc. 1988, 110, 5959–5967. doi: 10.1021/ja00226a005
25. [25]
  Clark, M.; Cramer, R. D.; Jones, D. M.; Patterson, D. E.; Simeroth, P. E. Comparative molecular field analysis (CoMFA). 2. Toward its use with 3D-structural databases. Tetrahedron Comput. Method 1990, 3, 47–59. doi: 10.1016/0898-5529(90)90120-W
26. [26]
  Douglas, M. H.; Subhash, C. B.; Denise, M. Assessing model fit by cross-validation. J. Chem. Inf. Comput. Sci. 2003, 43, 579–586. doi: 10.1021/ci025626i
27. [27]
  Liu, D.; Zhang, W. J.; Xu, L. Quantitative structure-activity/property relationships for chiral hydroxy acids and amino acids. Acta Chim. Sinica 2009, 67, 145–150.
28. [28]
  Xia, S.; Feng, Y.; Cheng, J. G.; Luo, H. B.; Li, Z.; Li, Z. M. QAAR exploration on pesticides with high solubility: an investigation on sulfonylurea herbicide dimers formed through p-p stacking interactions. Chin. Chem. Let. 2014, 25, 973–977.
29. [29]
  Song, L. M. Educational Surveying. Wuhan: Huazhong Normal University Press 1991, p468.
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1.
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