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.
1. [1]
  Junjun Huang , Ran Chen , Yajian Huang , Hang Zhang , Anran Zheng , Qing Xiao , Dan Wu , Ruxia Duan , Zhi Zhou , Fei He , Wei Yi . Discovery of an enantiopure N-[2-hydroxy-3-phenyl piperazine propyl]-aromatic carboxamide derivative as highly selective α_1D/1A-adrenoceptor antagonist and homology modelling. Chinese Chemical Letters, 2024, 35(11): 109594-. doi: 10.1016/j.cclet.2024.109594
2. [2]
  Han-Min Wang , Yan-Chen Li , Lu-Lu Sun , Ming-Ye Tang , Jia Liu , Jiahao Cai , Lei Dong , Jia Li , Yi Zang , Hai-Hao Han , Xiao-Peng He . Protein-encapsulated long-wavelength fluorescent probe hybrid for imaging lipid droplets in living cells and mice with non-alcoholic fatty liver. Chinese Chemical Letters, 2024, 35(11): 109603-. doi: 10.1016/j.cclet.2024.109603
3. [3]
  Cailiang Yue , Nan Sun , Yixing Qiu , Linlin Zhu , Zhiling Du , Fuqiang Liu . A direct Z-scheme 0D α-Fe₂O₃/TiO₂ heterojunction for enhanced photo-Fenton activity with low H₂O₂ consumption. Chinese Chemical Letters, 2024, 35(12): 109698-. doi: 10.1016/j.cclet.2024.109698
4. [4]
  Kun Zhang , Ni Dan , Dan-Dan Ren , Ruo-Yu Zhang , Xiaoyan Lu , Ya-Pan Wu , Li-Lei Zhang , Hong-Ru Fu , Dong-Sheng Li . A small D-A molecule with highly heat-resisting room temperature phosphorescence for white emission and anti-counterfeiting. Chinese Journal of Structural Chemistry, 2024, 43(3): 100244-100244. doi: 10.1016/j.cjsc.2024.100244
5. [5]
  Yuanjiao Liu , Xiaoyang Zhao , Songyao Zhang , Yi Wang , Yutuo Zheng , Xinrui Miao , Wenli Deng . Site-selection and recognition of aromatic carboxylic acid in response to coronene and pyridine derivative. Chinese Chemical Letters, 2024, 35(8): 109404-. doi: 10.1016/j.cclet.2023.109404
6. [6]
  An Lu , Yuhao Guo , Yi Yan , Lin Zhai , Xiangyu Wang , Weiran Cao , Zijie Li , Zhixia Zhao , Yujie Shi , Yuanjun Zhu , Xiaoyan Liu , Huining He , Zhiyu Wang , Jian-Cheng Wang . Nanomedicine integrating the lipidic derivative of 5-fluorouracil, miriplatin and PD-L1 siRNA for enhancing tumor therapy. Chinese Chemical Letters, 2024, 35(6): 108928-. doi: 10.1016/j.cclet.2023.108928
7. [7]
  Junying Zhang , Ruochen Li , Haihua Wang , Wenbing Kang , Xing-Dong Xu . Photo-induced tunable luminescence from an aggregated amphiphilic ethylene-pyrene derivative in aqueous media. Chinese Chemical Letters, 2024, 35(6): 109216-. doi: 10.1016/j.cclet.2023.109216
8. [8]
  Yuexi Guo , Zhaoyang Li , Jingwei Dai . Charlie and the 3D Printing Chocolate Factory. University Chemistry, 2024, 39(9): 235-242. doi: 10.3866/PKU.DXHX202309067
9. [9]
  Luyan Shi , Ke Zhu , Yuting Yang , Qinrui Liang , Qimin Peng , Shuqing Zhou , Tayirjan Taylor Isimjan , Xiulin Yang . Phytic acid-derivative Co₂B-CoPO_x coralloidal structure with delicate boron vacancy for enhanced hydrogen generation from sodium borohydride. Chinese Chemical Letters, 2024, 35(4): 109222-. doi: 10.1016/j.cclet.2023.109222
10. [10]
  Xiongbo Song , Jinwen Xiao , Juan Wu , Li Sun , Long Chen . Decellularized amniotic membrane promotes the anti-inflammatory response of macrophages via PI3K/AKT/HIF-1α pathway. Chinese Chemical Letters, 2025, 36(1): 109844-. doi: 10.1016/j.cclet.2024.109844
11. [11]
  Runze Liu , Yankai Bian , Weili Dai . Qualitative and quantitative analysis of Brønsted and Lewis acid sites in zeolites: A combined probe-assisted 1H MAS NMR and NH3-TPD investigation. Chinese Journal of Structural Chemistry, 2024, 43(4): 100250-100250. doi: 10.1016/j.cjsc.2024.100250
12. [12]
  Yan Cheng , Hua-Peng Ruan , Yan Peng , Longhe Li , Zhenqiang Xie , Lang Liu , Shiyong Zhang , Hengyun Ye , Zhao-Bo Hu . Magnetic, dielectric and luminescence synergetic switchable effects in molecular material [Et₃NCH₂Cl]₂[MnBr₄]. Chinese Chemical Letters, 2024, 35(4): 108554-. doi: 10.1016/j.cclet.2023.108554
13. [13]
  Jie XIE , Hongnan XU , Jianfeng LIAO , Ruoyu CHEN , Lin SUN , Zhong JIN . Nitrogen-doped 3D graphene-carbon nanotube network for efficient lithium storage. Chinese Journal of Inorganic Chemistry, 2024, 40(10): 1840-1849. doi: 10.11862/CJIC.20240216
14. [14]
  Xi Xu , Chaokai Zhu , Leiqing Cao , Zhuozhao Wu , Cao Guan . Experiential Education and 3D-Printed Alloys: Innovative Exploration and Student Development. University Chemistry, 2024, 39(2): 347-357. doi: 10.3866/PKU.DXHX202308039
15. [15]
  Qiang Zhou , Pingping Zhu , Wei Shao , Wanqun Hu , Xuan Lei , Haiyang Yang . Innovative Experimental Teaching Design for 3D Printing High-Strength Hydrogel Experiments. University Chemistry, 2024, 39(6): 264-270. doi: 10.3866/PKU.DXHX202310064
16. [16]
  Changyuan Bao , Yunpeng Jiang , Haoyin Zhong , Huaizheng Ren , Junhui Wang , Binbin Liu , Qi Zhao , Fan Jin , Yan Meng Chong , Jianguo Sun , Fei Wang , Bo Wang , Ximeng Liu , Dianlong Wang , John Wang . Synergizing 3D-printed structure and sodiophilic interface enables highly efficient sodium metal anodes. Chinese Chemical Letters, 2024, 35(11): 109353-. doi: 10.1016/j.cclet.2023.109353
17. [17]
  Chengmin Hu , Pingxuan Liu , Ziyang Song , Yaokang Lv , Hui Duan , Li Xie , Ling Miao , Mingxian Liu , Lihua Gan . Tailor-made overstable 3D carbon superstructures towards efficient zinc-ion storage. Chinese Chemical Letters, 2025, 36(4): 110381-. doi: 10.1016/j.cclet.2024.110381
18. [18]
  Yuan Teng , Zichun Zhou , Jinghua Chen , Siying Huang , Hongyan Chen , Daibin Kuang . Dual atom-bridge effect promoting interfacial charge transfer in 2D/2D Cs₃Bi₂Br₉/BiOBr epitaxial heterojunction for efficient photocatalysis. Chinese Chemical Letters, 2025, 36(2): 110430-. doi: 10.1016/j.cclet.2024.110430
19. [19]
  Hualin Jiang , Wenxi Ye , Huitao Zhen , Xubiao Luo , Vyacheslav Fominski , Long Ye , Pinghua Chen . Novel 3D-on-2D g-C₃N₄/AgI._x._y heterojunction photocatalyst for simultaneous and stoichiometric production of H₂ and H₂O₂ from water splitting under visible light. Chinese Chemical Letters, 2025, 36(2): 109984-. doi: 10.1016/j.cclet.2024.109984
20. [20]
  Hui Peng , Xiao Wang , Weiguo Huang , Shuiyue Yu , Linghang Kong , Qilin Wei , Jialong Zhao , Bingsuo Zou . Efficient tunable visible and near-infrared emission in Sb³⁺/Sm³⁺-codoped Cs₂NaLuCl₆ for near-infrared light-emitting diode, triple-mode fluorescence anti-counterfeiting and information encryption. Chinese Chemical Letters, 2024, 35(11): 109462-. doi: 10.1016/j.cclet.2023.109462

Get Citation

PDF

XML

Metrics

PDF Downloads(1)
Abstract views(299)
HTML views(5)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142