Citation: Hui FENG, Chang-Jun FENG, Jing-Pei CAO. Study on the Biological Activity of 3-Aroyl-5-substituted Thiophene Derivatives Based on the CoMFA Method[J]. Chinese Journal of Structural Chemistry, ;2020, 39(11): 1978-1984. doi: 10.14102/j.cnki.0254–5861.2011–2703 shu

Study on the Biological Activity of 3-Aroyl-5-substituted Thiophene Derivatives Based on the CoMFA Method

Hui FENG ^{a, b} ,
Chang-Jun FENG ^b ,
Jing-Pei CAO ^a,,

a.
Key Laboratory of Coal Processing and Efﬁcient Utilization (Ministry of Education), Xuzhou 221116, China
b.
School of Chemistry & Chemical Engineering, Xuzhou University of Technology, Xuzhou 221018, China

Corresponding author: Jing-Pei CAO, caojingpei@cumt.edu.cn
Received Date: 17 December 2019
Accepted Date: 17 February 2020

Fund Project: the National Natural Science Foundation of China 21676292the National Natural Science Foundation of China 21075138special fund of State Key Laboratory of Structure Chemistry 2016028

Figures(3)

A three-dimensional quantitative structure-activity relationship (3D-QSAR) study was conducted to analyze the A1AR density (B_max) of 56 3-aroyl-5-substituted thiophene derivatives (ASTDs) in human A1 Chinese hamster ovary (hA1CHO) membranes by the comparative molecular field analysis (CoMFA) method. A training set of 45 compounds was used to establish the predictive model, which was verified by the test set of 17 compounds containing template molecule and 5 newly designed molecules. The cross-validation (R_cv²) and non-cross-validation (R²) coefficients of the training set were 0.655 and 0.959, respectively. The model was used to predict the activities of the compounds of the training and test sets, and the results indicated that the models had strong stability and good prediction ability. According to model analysis, the contribution of steric and electrostatic fields was 51.4% and 48.6%, respectively. Based on the 3D contour maps, five excellent ASTDs agonists were designed, which need to be further verified by biomedical experiments.
1. [1]
  Ke, Y. R.; Jin, H. W; Liu, Z. M.; Zhang, L. R. Homology modeling and structure validation of the adenosine A1 receptor. Acta Phys. -Chim. Sin. 2010, 26, 2833–2839. doi: 10.3866/PKU.WHXB20100916
2. [2]
  Romagnoli, R.; Baraldi, P. G.; Carrion, M. D.; Cruz-Lopez, O.; Cara, C. L.; Saponaro, G.; Preti, D.; Tabrizi, M. A.; Baraldi, S.; Moorman, A. R.; Vincenzi, F.; Borea, P. A.; Varani, K. Synthesis and biological evaluation of novel 2-amino-3-aroyl-4-neopentyl-5-substituted thiophene derivatives as allosteric enhancers of the A₁ adenosine receptor. Bioorgan. Med. Chem. 2014, 22, 148–166. doi: 10.1016/j.bmc.2013.11.043
3. [3]
  Feng, C. J. Quantitative Structure-efficacy Relationship and Its Applications. China University of Mining and Technology Press, Xuzhou 2017, p1–26.
4. [4]
  Wang, C.; Feng, C. J. QSAR study of the action strength of D_OM of phenyl-isopropyl-amine dopes using MLR and BP-ANN. Chin. J. Struct. Chem. 2017, 36, 1720–1728.
5. [5]
  Wang, C.; Feng, C. J. QSAR studies on the inhibitory activity of levofloxacin-thiadiazole HDACi conjugates to histone deacetylases. Chin. J. Struct. Chem. 2018, 37, 1679–1688.
6. [6]
  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. Environ. Chem. 2019, 38, 1005–1013.
7. [7]
  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
8. [8]
  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
9. [9]
  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.
10. [10]
  Feng, H.; Feng C. J. 3D-QSAR studies on the anti-tumor activity of N-aryl-salicylamide derivatives. Chin. J. Struct. Chem. 2019, 38, 1874–1880.
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]
  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.
13. [13]
  Tong, J. B.; Wang, Y.; Lei, S.; Qin, S. S. 3D-QSAR and docking studies of 1, 3, 4-thiazolidinone derivatives using R-group search and surflex-dock. Chin. J. Struct. Chem. 2019, 38, 464–475.
14. [14]
  Tong, J. B.; Wang, Y.; Lei, S.; Qin, S. S. Comprehensive 3D-QSAR and binding mode of DAPY inhibitors using R-group search and molecular docking. Chin. J. Struct. Chem. 2019, 38, 25–36.
15. [15]
  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.
16. [16]
  Tong, J.; 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. doi: 10.1002/cem.2809
17. [17]
  Liu, H. X.; Shi, J. Q.; Liu, H.; Wang, Z. Y. Improved 3D-QSPR analysis of the predictive octanol-air partition coefficients of hydroxylated and methoxylated polybrominated diphenyl ethers. Atmos. Environ. 2013, 77, 840–845. doi: 10.1016/j.atmosenv.2013.05.068
18. [18]
  Wang, X. Y.; Duan, W. G.; Lin, G. S.; Kang, G. Q.; Shang, M. H.; Lei, F. H. Synthesis and antifungal activity of (Z)-/(E)-verbenone oxime ether compounds. Chem. Ind. Forest Prod. 2019, 39, 27–34.
19. [19]
  Baraldi, P. G.; Borea, P. A.; Bergonzoni, M.; Cacciari, B.; Ongini, E.; Recanatini, M.; Spalluto, G. Comparative molecular field analysis (CoMFA) of a series of selective adenosine receptor A2A antagonists. Drug Dev. Res. 1999, 46, 126–133. doi: 10.1002/(SICI)1098-2299(199902)46:2<126::AID-DDR5>3.0.CO;2-7
20. [20]
  Feng, C. J. CoMFA model of herbicidal activity of phenyl-sulfonylured derivatives. J. Xuzhou Inst. Tech. (Nat. Sci. Ed. ) 2019, 34, 21–25.
21. [21]
  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.
22. [22]
  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.
23. [23]
  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. Methodol. 1990, 3, 47–59.
24. [24]
  Cramer, R. D.; Burce J. D.; Patterson D. E.; Frank, I. E. Cross-validation, boot strapping, and partial least squares compared with multiple regression in conventional QSAR study. Quant. Struct. -Act. Relat. 1988, 7, 18–25.
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