Citation: Hui FENG, Chang-Jun FENG. CoMFA Model of Anti-tumor Activity for Fluoroquinolon-3-yl s-Triazole Sulfide-ketone Derivatives and Implications for Molecular Design[J]. Chinese Journal of Structural Chemistry, ;2021, 40(6): 703-710. doi: 10.14102/j.cnki.0254–5861.2011–3000 shu

CoMFA Model of Anti-tumor Activity for Fluoroquinolon-3-yl s-Triazole Sulfide-ketone Derivatives and Implications for Molecular Design

Hui FENG ,
Chang-Jun FENG ^,

School of Chemistry & Chemical Engineering, Xuzhou University of Technology, Xuzhou 221018, China

Corresponding author: Chang-Jun FENG, fengcj@xzit.edu.cn
Received Date: 12 October 2020
Accepted Date: 26 November 2020

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

Figures(6)

Comparative molecular field analysis (CoMFA) techniques were used to perform three-dimensional quantitative structure-activity relationship (3D-QSAR) studies on the anti-tumor activity (pI_H and pI_C) of 28 fluoroquinolon-3-yl s-triazole sulfide-ketone derivatives (FQTSDs) against two cancer cell lines, including human hepatoma Hep-3B cells and human pancreatic cancer Capan-1 cells. 23 compounds were randomly selected as the training set to establish the prediction models, which were verified by the test set of 6 compounds containing template molecule. The obtained cross-validation (R_cv²) and non-cross-validation correlation coefficients (R²) of the CoMFA models were 0.477 and 0.850 for pI_H, and 0.421 and 0.836 for pI_C, respectively. The contributions of steric and electrostatic fields to pI_H were determined to be 48.1% and 51.9%, and those to pI_C were 49.4% and 50.6%, respectively. The CoMFA models were then used to predict the activities of the compounds in the training and testing sets, and the models had a strong stability and good predictability. Based on the 3D contour maps, four novel FQTSDs with a higher anti-tumor activity were designed. However, the effectiveness of these novel FQTSDs is still needed to be verified by experimental results.
- fluoroquinolon-3-yl s-triazole sulfide-ketone derivative,
- anti-tumor activity,
- 3D-QSAR,
- comparative molecular field analysis,
- molecular design
1. [1]
  Mayer, C.; Janin, Y. L. Non-quinolone inhibitors of bacterial type IIA topoisomerases: a feat of bioisosterism. Chem. Rev. 2014, 114, 2313-2342. doi: 10.1021/cr4003984
2. [2]
  Zhou, Y.; Xu, X.; Sun, Y.; Wang, H. P.; Sun, H. P.; You, Q. D. Synthesis, cytotoxicity and topoisomerase II inhibitory activity of lomefloxacin derivatives. Bioorg. Med. Chem. Lett. 2013, 23, 2974-2978. doi: 10.1016/j.bmcl.2013.03.037
3. [3]
  Pirhadi, S.; Shiri, F.; Ghasemi, J. B. Methods and applications of structure-based pharmacophores in drug discovery. Curr. Top. Med. Chem. 2013, 13, 1036-1047. doi: 10.2174/1568026611313090006
4. [4]
  Guo, Z. R. Strategy of molecular drug design: activity and druggability. Acta Pharm. Sin. 2010, 45, 539-547.
5. [5]
  Gao, L. Z.; Xie, Y. S.; Li, T.; Huang, W. T.; Hu, G. Q. Synthesis, antitumor activity and SAR of C-3 oxadiazole sulfanylacetylhydrazone-substituted fluoroquinolone analogues. Acta Pharm. Sin. 2014, 49, 1694-1698.
6. [6]
  Ni, L. L.; Yan, Q.; Wu, S. M.; Xie, Y. S.; Gao, L. Z.; Liu, Y. J.; Huang, W. L.; Hu, G. Q. Synthesis and antitumor activity of fluoroquinolon-3-yl-s-triazole sulfide ketones and their derivatives from ciprofloxacin. Acta Pharm. Sin. 2015, 50, 1258-1262.
7. [7]
  Xie, Y. S.; Gao, L. Z.; Yan, Q.; Wu, S. M.; Ni, L. L.; Liu, Y. J.; Huang, W. L.; Hu, G. Q. Synthesis and antitumor activity of fluoroquinolon-3-yl s-triazole sulfide-ketone thiosemicarbazone derivatives of ofloxacin. Chin. J. Appl. Chem. 2016, 33, 25-31.
8. [8]
  Abdulla, A. M.; Mei, Z.; Qiu, L.; Ju, X. H. Theoretical investigation on QSAR of (2-methyl-3-biphenylyl) methanol analogs as PD-L1 inhibitor. Chin. J. Chem. Phys. 2020, 33, 459-467. doi: 10.1063/1674-0068/cjcp1909168
9. [9]
  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.
10. [10]
  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
11. [11]
  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. Engin. Data 2012, 57, 2442-2455. doi: 10.1021/je300407g
12. [12]
  Zeng, X. L.; Qu, R. J.; Feng, M. B.; Chen, J.; Wang, L. S.; Wang, Z. Y. Photodegradation of polyfluorinated dibenzo-p-dioxins (PFDDs) in organic solvents: experimental and theoretical studies. Environ. Sci. Technol. 2016, 50, 8128-8134. doi: 10.1021/acs.est.6b02682
13. [13]
  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
14. [14]
  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.
15. [15]
  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.
16. [16]
  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.
17. [17]
  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.
18. [18]
  Guo, Z. R. Molecular Drug Design. Science press. Beijing 2005, p20.
19. [19]
  Feng, C. J. CoMFA model of herbicidal activity of phenyl-sulfonylured derivatives. J. Xuzhou Inst. Tech. (Nat. Sci. Ed. ) 2019, 34, 21-25.
20. [20]
  Feng, C. J. CoMFA model of inhibitory activity for nitrobenzene derivatives to photobacteria. J. Xuzhou Inst. Tech. (Nat. Sci. Ed. ) 2020, 35, 28-31.
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. doi: 10.1007/s00044-013-0607-3
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. doi: 10.1021/ja00226a005
23. [23]
  Hu, S. Q.; Mi, S. Q.; Jia, X. L.; Guo, A. L.; Chen, S. H.; Zhang, J.; Liu, X. Y. 3D-QSAR study and molecular design of benzimidazole derivatives as corrosion inhibitors. Chem. J. Chin. Univ. 2011, 32, 2402-2409.
24. [24]
  Liu, D.; Zhang, W.; Xu, L. Quantitative structure-activity/property relationships for chiral hydroxy acids and amino acids. Acta Chim. Sin. 2009, 67, 145-150.
25. [25]
  Zhang, J.; Shen, P.; Lu, T.; Yu, D.; Li, H.; Yang, G. Theoretical studies on quantitative structure-activity relationship and structural modification for the inhibition of MMP-9 by flavonoids. Acta Chim. Sin. 2011, 69, 383-392.
26. [26]
  Anshuman, D.; Sushil, K. K.; Stuti, G.; Anil, K. S. Development of CoMFA, advance CoMFA and CoMSIA models in pyrroloquinazolines as thrombin receptor antagonist. Bioorg. Medic. Chem. 2004, 12, 3591-3598.
27. [27]
  Sun, W. S.; Chen, L. C. Statistics (Second edition). China agricultural university press. Beijing 2012, p241, 242, 470.
1. [1]
  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
2. [2]
  Huanyan Liu , Jiajun Long , Hua Yu , Shichao Zhang , Wenbo Liu . Rational design of highly conductive and stable 3D flexible composite current collector for high performance lithium-ion battery electrodes. Chinese Chemical Letters, 2025, 36(3): 109712-. doi: 10.1016/j.cclet.2024.109712
3. [3]
  Fang-Yuan Chen , Wen-Chao Geng , Kang Cai , Dong-Sheng Guo . Molecular recognition of cyclophanes in water. Chinese Chemical Letters, 2024, 35(5): 109161-. doi: 10.1016/j.cclet.2023.109161
4. [4]
  Caihong Mao , Yanfeng He , Xiaohan Wang , Yan Cai , Xiaobo Hu . Synthesis and molecular recognition characteristics of a tetrapodal benzene cage. Chinese Chemical Letters, 2024, 35(8): 109362-. doi: 10.1016/j.cclet.2023.109362
5. [5]
  Cheng-Da Zhao , Huan Yao , Shi-Yao Li , Fangfang Du , Li-Li Wang , Liu-Pan Yang . Amide naphthotubes: Biomimetic macrocycles for selective molecular recognition. Chinese Chemical Letters, 2024, 35(4): 108879-. doi: 10.1016/j.cclet.2023.108879
6. [6]
  Yanwei Duan , Qing Yang . Molecular targets and their application examples for interrupting chitin biosynthesis. Chinese Chemical Letters, 2025, 36(4): 109905-. doi: 10.1016/j.cclet.2024.109905
7. [7]
  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
8. [8]
  Zhimin Sun , Xin-Hui Guo , Yue Zhao , Qing-Yu Meng , Li-Juan Xing , He-Lue Sun . Dynamically switchable porphyrin-based molecular tweezer for on−off fullerene recognition. Chinese Chemical Letters, 2024, 35(6): 109162-. doi: 10.1016/j.cclet.2023.109162
9. [9]
  Li Lin , Song-Lin Tian , Zhen-Yu Hu , Yu Zhang , Li-Min Chang , Jia-Jun Wang , Wan-Qiang Liu , Qing-Shuang Wang , Fang Wang . Molecular crowding electrolytes for stabilizing Zn metal anode in rechargeable aqueous batteries. Chinese Chemical Letters, 2024, 35(7): 109802-. doi: 10.1016/j.cclet.2024.109802
10. [10]
  Minghao Hu , Tianci Xie , Yuqiang Hu , Longjie Li , Ting Wang , Tongbo Wu . Allosteric DNAzyme-based encoder for molecular information transfer. Chinese Chemical Letters, 2024, 35(7): 109232-. doi: 10.1016/j.cclet.2023.109232
11. [11]
  Chuan-Zhi Ni , Ruo-Ming Li , Fang-Qi Zhang , Qu-Ao-Wei Li , Yuan-Yuan Zhu , Jie Zeng , Shuang-Xi Gu . A chiral fluorescent probe for molecular recognition of basic amino acids in solutions and cells. Chinese Chemical Letters, 2024, 35(10): 109862-. doi: 10.1016/j.cclet.2024.109862
12. [12]
  Wei-Jia Wang , Kaihong Chen . Molecular-based porous polymers with precise sites for photoreduction of carbon dioxide. Chinese Chemical Letters, 2025, 36(1): 109998-. doi: 10.1016/j.cclet.2024.109998
13. [13]
  Dongpu Wu , Zheng Yang , Yuchen Xia , Lulu Wu , Yingxia Zhou , Caoyuan Niu , Puhui Xie , Xin Zheng , Zhanqi Cao . Surface controllable wettability using amphiphilic rotaxane molecular shuttles. Chinese Chemical Letters, 2025, 36(2): 110353-. doi: 10.1016/j.cclet.2024.110353
14. [14]
  Bingwei Wang , Yihong Ding , Xiao Tian . Benchmarking model chemistry composite calculations for vertical ionization potential of molecular systems. Chinese Chemical Letters, 2025, 36(2): 109721-. doi: 10.1016/j.cclet.2024.109721
15. [15]
  Kai Ye , Zhicheng Ye , Chuantao Wang , Zhilai Luo , Cheng Lian , Chunyan Bao . Artificial signal transduction triggered by molecular photoisomerization in lipid membranes. Chinese Chemical Letters, 2025, 36(4): 110033-. doi: 10.1016/j.cclet.2024.110033
16. [16]
  Linping Li , Junhui Su , Yanping Qiu , Yangqin Gao , Ning Li , Lei Ge . Design and fabrication of ternary Au/Co3O4/ZnCdS spherical composite photocatalyst for facilitating efficient photocatalytic hydrogen production. Chinese Journal of Structural Chemistry, 2024, 43(12): 100472-100472. doi: 10.1016/j.cjsc.2024.100472
17. [17]
  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
18. [18]
  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
19. [19]
  Qihan Lin , Jiabin Xing , Yue-Yang Liu , Gang Wu , Shi-Jia Liu , Hui Wang , Wei Zhou , Zhan-Ting Li , Dan-Wei Zhang . taBOX: A water-soluble tetraanionic rectangular molecular container for conjugated molecules and taste masking for berberine and palmatine. Chinese Chemical Letters, 2024, 35(5): 109119-. doi: 10.1016/j.cclet.2023.109119
20. [20]
  Zhikang Wu , Guoyong Dai , Qi Li , Zheyu Wei , Shi Ru , Jianda Li , Hongli Jia , Dejin Zang , Mirjana Čolović , Yongge Wei . POV-based molecular catalysts for highly efficient esterification of alcohols with aldehydes as acylating agents. Chinese Chemical Letters, 2024, 35(8): 109061-. doi: 10.1016/j.cclet.2023.109061

Get Citation

PDF

XML

Metrics

PDF Downloads(1)
Abstract views(306)
HTML views(3)

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