Citation: Jian-Cheng SHI, Xiao-Qian HUANG, Min LUO, Chu-Sheng HUANG. Identification of Novel and Potent Curcuminoids Inhibitors of Tubulin with Anticancer Activities by 3D-QSAR and Molecular Docking[J]. Chinese Journal of Structural Chemistry, ;2020, 39(6): 1157-1166. doi: 10.14102/j.cnki.0254-5861.2011-2545 shu

Identification of Novel and Potent Curcuminoids Inhibitors of Tubulin with Anticancer Activities by 3D-QSAR and Molecular Docking

College of Chemistry and Material, Nanning Normal University, Nanning 530001, China

Corresponding author: Chu-Sheng HUANG, wyc666999@sina.cn
Received Date: 23 July 2019
Accepted Date: 9 January 2020

Fund Project: National Natural Science Foundation of China 21702034National Natural Science Foundation of China 21861007the Research Foundation of Education Bureau of Guangxi Province 200103YB076Natural Science Foundation of Guangxi Province 2017GXNSFBA198089

Figures(9)

The three-dimensional quantitative structure-activity relationships (3D-QSAR) for 37 curcumin derivatives were constructed by CoMFA and CoMSIA methods, respectively. The results showed that the cross validated coefficient (q²) and non-cross-validated coefficient (R²) were 0.711, 0.962 in CoMFA model and 0.774, 0.856 in CoMSIA model, respectively, which suggests that two models are robust and have good exterior predictive capabilities. Based on these two models and the binding mode with tubulin, nine novel curcuminoids inhibitors which could exhibit much higher anticancer potency and efficiently occupy the colchicine binding site of tubulin, were designed. We expect that the results in this paper have the potential to facilitate the process of design and to develop new potent curcumin derivatives with stronger anticancer activities.
- anticancer activity,
- tubulin,
- curcumin derivatives,
- 3D-QSAR,
- molecular docking,
- molecular design
1. [1]
  Wang, R. B.; Zhang, X. J.; Chen, C. S.; Chen, G. L.; Sarabia, C.; Zhang, Q.; Zheng, S. L.; Wang, G. D.; Chen Q. H. Structure-activity relationship studies of 1, 7-diheteroarylhepta-1, 4, 6-trien-3-ones with two different terminal rings in prostate epithelialcell models. Eur. J. Med. Chem. 2017, 133, 208–226. doi: 10.1016/j.ejmech.2017.03.067
2. [2]
  Teiten, M. H.; Gaascht, F.; Eifes, S.; Dicato, M.; Diederich, M. Chemopreventive potential of curcumin in prostate cancer. Genes Nutr. 2010, 5, 61–74. doi: 10.1007/s12263-009-0152-3
3. [3]
  Chen, Q. H. Curcumin-based anti-prostate cancer agents. Anticancer Agents Med. Chem. 2015, 15, 138–156. doi: 10.2174/1871520615666150116102442
4. [4]
  Li, H. H.; Liu, T.; Xuan, H. X.; Fang, S. B.; Zhao, C. Y. A combination of pharmacophore modeling, virtual screening, and molecular docking studies for a diverse set of colchicine site inhibitors. Med. Chem. Res. 2014, 23, 4713–4723. doi: 10.1007/s00044-014-1028-7
5. [5]
  Prise, V. E.; Honess, D. J.; Stratford, M. R. L.; Wilson, J.; Tozer, G. M. The vascular response of tumor and normal tissues in the rat to the vascular targeting agent, combretastatin A-4-phosphate, at clinically relevant doses. Int. J. Oncol. 2002, 21, 717–726.
6. [6]
  Tozer, G. M.; Kanthou, C.; Parkins, C. S.; Hill, S. A. The biology of the combretastatins as tumour vascular targeting agents. Int. J. Exp. Pathol. 2002, 83, 21–38. doi: 10.1046/j.1365-2613.2002.00211.x
7. [7]
  Lu, Y.; Chen, J.; Xiao, M.; Li, W.; Miller, D. D. An overview of tubulin inhibitors that interact with the colchicine binding site. Pharm. Res. 2012, 29, 2943–2971. doi: 10.1007/s11095-012-0828-z
8. [8]
  Nakagawa-Goto, K.; Oda, A.; Hamel, E.; Ohkoshi, E.; Lee, K. H.; Goto, M. Development of a novel class of tubulin inhibitor from desmosdumotin B with a hydroxylated bicyclic B-ring. J. Med. Chem. 2015, 58, 2378–2389. doi: 10.1021/jm501859j
9. [9]
  Yang, J. H.; Yan, W.; Yu, Y. M.; Wang, Y. X.; Yang, T.; Xue, L. L.; Yuan, X.; Long, C. F.; Liu, Z. W.; Chen, X. X.; Hu, M. S.; Zheng, L.; Qiu, Q.; Pei, H. Y.; Li, D.; Wang, F.; Bai, P.; Wen, J. L.; Ye, H. Y.; Chen, L. J. The compound millepachine and its derivatives inhibit tubulin polymerization by irreversibly binding to the colchicine-binding site in β-tubulin. J. Biol. Chem. 2018, 293, 9461–9472. doi: 10.1074/jbc.RA117.001658
10. [10]
  Massarotti, A.; Coluccia, A.; Silvestri, R.; Sorba, G.; Brancale, A. The tubulin colchicine domain: a molecular modeling perspective. Chem. Med. Chem. 2012, 7, 33-42. doi: 10.1002/cmdc.201100361
11. [11]
  Li, L.; Jiang, S.; Li, X.; Liu, Y.; Su, J.; Chen, J. Recent advances in trimethoxyphenyl (TMP) based tubulin inhibitors targeting the colchicine binding site. Eur. J. Med. Chem. 2018, 151, 482–494. doi: 10.1016/j.ejmech.2018.04.011
12. [12]
  Liu, G. P.; Jiao, Y.; Huang, C. X.; Chang, P. Identification of novel and potent small molecule inhibitors of tubulin with antitumor activities by virtual screening and biological evaluations. J. Comput. Aided Mol. Des. 2019, 33, 659–664. doi: 10.1007/s10822-019-00206-y
13. [13]
  Joshi, P.; Tanwar, O.; Rambhade, S.; Bhaisare, M.; Jain, D. 2-D QSAR studies of steroidal natural products oleanic acid and their semisynthetic derivatives as potent protein tyrosine phosphatase 1B inhibitors. Med. Chem. Res. 2012, 21, 351–361. doi: 10.1007/s00044-010-9529-5
14. [14]
  III 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
15. [15]
  Kubinyi, H. Ed. 3D QSAR in Drug Design: Theory, Methods and Applications. ESCOM Science Publishers: Leiden 1993.
16. [16]
  Lu, Y. K.; Wang, J.; Hu, Y.; Lin, Y.; Lin, Z. H. Molecular modeling studies of vascular endothelial growth factor receptor tyrosine kinase inhibitors combining molecular docking and 3D-QSAR methods. Chin. J. Struct. Chem. 2013, 5, 679–694.
17. [17]
  Gerhard, K.; Abraham, U.; Thomas, M. Molecular similarity indices in a comparative analysis (CoMSIA) of drug molecules to correlate and predict their biological activity. J. Med. Chem. 1994, 37, 4130–4146. doi: 10.1021/jm00050a010
18. [18]
  Cao, H. Y.; Zhang, H. B.; Zheng, X. F.; Gao, D. B. 3D QSAR studies on a series of potent and high selective inhibitors for three kinases of RTK family. J. Mol. Graphics Model. 2007, 26, 236–245. doi: 10.1016/j.jmgm.2006.12.001
19. [19]
  Leong, S. W.; Chia, S. L.; Abas, F.; Yusoff, K. Asymmetrical meta-methoxylated diarylpentanoids: rational design, synthesis and anti-cancer evaluation in-vitro. Eur. J. Med. Chem. 2018, 157, 716–728. doi: 10.1016/j.ejmech.2018.08.039
20. [20]
  Ravelli, R. B. G.; Gigant, B.; Curmi, P. A.; Jourdain, I.; Lachkar, S.; Sobel, A.; Knossow, M. Insight into tubulin regulation from a complex with colchicine and a stathmin-like domain. Nature 2004, 428, 198–202. doi: 10.1038/nature02393
21. [21]
  Lv, Y. Y.; Yin, C. S.; Liu, H. Y.; Yi, Z. S.; Wang, Y. 3D-QSAR study on atmospheric half-lives of POPs using CoMFA and CoMSIA. J. Environ. Sci. 2008, 20, 1433–1438. doi: 10.1016/S1001-0742(08)62545-0
22. [22]
  SYBYL X-2.0, Tripos Inc., St. Louis, Missouri 2012.
23. [23]
  Clark, M.; Cramer, R. D. I.; van Opdenbosch, N. Validation of the general purpose Tripos 5.2 force field. J. Comput. Chem. 1989, 10, 982–1012. doi: 10.1002/jcc.540100804
24. [24]
  Gasteiger, J.; Marsili, M. Iterative partial equalization of orbital electronegativity: a rapid access to atomic charges. Tetrahedron 1980, 36, 3219–3228. doi: 10.1016/0040-4020(80)80168-2
25. [25]
  Pandey, A.; Mungalpara, J.; Mohan, C. G. Comparative molecular field analysis and comparative molecular similarity indices analysis of hydroxyethylamine derivatives as selective human BACE-1 inhibitor. Mol. Divers. 2010, 14, 39–49. doi: 10.1007/s11030-009-9139-7
26. [26]
  Clark, M.; Cramer, R. D.; Opdenbosch, V. N. Validation of the general purpose Tripos 5.2 force field. J. Comput. Chem. 1989, 10, 982–1012. doi: 10.1002/jcc.540100804
27. [27]
  Cramer, R. D.; Bunce, J. D.; Patterson, D. E. Cross-validation, bootstrapping, and partial least squares compared with multiple regression in conventional QSAR studies. Quant. Struct. -Act. Relat. 1988, 7, 18–25. doi: 10.1002/qsar.19880070105
28. [28]
  Huang, C. S.; Tu, W. T.; Luo, M.; Shi, J. C. Molecular docking and design of novel heterodimers of donepezil and huperzine fragments as acetylcholinesterase inhibitors. Chin. J. Struct. Chem. 2016, 35, 839–848.
29. [29]
  Shi, J. C.; Zhao, D.; Luo, M.; Huang, C. S. A mechanism-based 3D-QSAR and DFT approach for the prediction of H5N1 entry inhibitory potency of 3-O-β-chacotriosyl ursolic acid derivatives. Chin. J. Struct. Chem. 2017, 36, 1987–1999.
30. [30]
  Tropsha, A.; Golbraikh, A. Beware of q²! J. Mol. Graph. Model. 2002, 20, 269–276. doi: 10.1016/S1093-3263(01)00123-1
31. [31]
  Joshi, P.; Tanwar, O.; Rambhade, S.; Bhaisare, M.; Jain, D. 2-D QSAR studies of steroidal natural products oleanic acid and their semisynthetic derivatives as potent protein tyrosine phosphatase 1B inhibitors. Med. Chem. Res. 2012, 21, 351–361. doi: 10.1007/s00044-010-9529-5
32. [32]
  Roy, K. On some aspects of validation of predictive quantitative structure-activity relationship models. Expert. Opin. Drug Discov. 2007, 2, 1567–1577. doi: 10.1517/17460441.2.12.1567
1. [1]
  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
2. [2]
  Bairu Meng , Zongji Zhuo , Han Yu , Sining Tao , Zixuan Chen , Erik De Clercq , Christophe Pannecouque , Dongwei Kang , Peng Zhan , Xinyong Liu . Design, synthesis, and biological evaluation of benzo[4,5]thieno[2,3-d]pyrimidine derivatives as novel HIV-1 NNRTIs. Chinese Chemical Letters, 2024, 35(6): 108827-. doi: 10.1016/j.cclet.2023.108827
3. [3]
  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
4. [4]
  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
5. [5]
  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
6. [6]
  Wenyi Mei , Lijuan Xie , Xiaodong Zhang , Cunjian Shi , Fengzhi Wang , Qiqi Fu , Zhenjiang Zhao , Honglin Li , Yufang Xu , Zhuo Chen . Design, synthesis and biological evaluation of fluorescent derivatives of ursolic acid in living cells. Chinese Chemical Letters, 2024, 35(5): 108825-. doi: 10.1016/j.cclet.2023.108825
7. [7]
  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
8. [8]
  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
9. [9]
  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
10. [10]
  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
11. [11]
  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
12. [12]
  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
13. [13]
  Jinyan Zhang , Fen Liu , Qian Jin , Xueyi Li , Qiong Zhan , Mu Chen , Sisi Wang , Zhenlong Wu , Wencai Ye , Lei Wang . Discovery of unusual phloroglucinol–triterpenoid adducts from Leptospermum scoparium and Xanthostemon chrysanthus by building blocks-based molecular networking. Chinese Chemical Letters, 2024, 35(6): 108881-. doi: 10.1016/j.cclet.2023.108881
14. [14]
  Zixi Zou , Jingyuan Wang , Yian Sun , Qian Wang , Da-Hui Qu . Controlling molecular assembly on time scale: Time-dependent multicolor fluorescence for information encryption. Chinese Chemical Letters, 2024, 35(7): 108972-. doi: 10.1016/j.cclet.2023.108972
15. [15]
  Ruonan Guo , Heng Zhang , Changsheng Guo , Ningqing Lv , Beidou Xi , Jian Xu . Degradation of neonicotinoids with different molecular structures in heterogeneous peroxymonosulfate activation system through different oxidation pathways. Chinese Chemical Letters, 2024, 35(9): 109413-. doi: 10.1016/j.cclet.2023.109413
16. [16]
  Wei-Yu Zhou , Zi-Han Xi , Ning-Ning Du , Li Ye , Ming-Hao Jiang , Jin-Le Hao , Bin Lin , Guo-Dong Yao , Xiao-Xiao Huang , Shao-Jiang Song . Rapid discovery of two unprecedented meroterpenoids from Daphne altaica Pall. using molecular networking integrated with MolNetEnhancer and Network Annotation Propagation. Chinese Chemical Letters, 2024, 35(8): 109030-. doi: 10.1016/j.cclet.2023.109030
17. [17]
  Hualei Xu , Manman Han , Haiqiang Liu , Liang Qin , Lulu Chen , Hao Hu , Ran Wu , Chenyu Yang , Hua Guo , Jinrong Li , Jinxiang Fu , Qichen Hao , Yijun Zhou , Jinchao Feng , Xiaodong Wang . 4-Nitrocatechol as a novel matrix for low-molecular-weight compounds in situ detection and imaging in biological tissues by MALDI-MSI. Chinese Chemical Letters, 2024, 35(6): 109095-. doi: 10.1016/j.cclet.2023.109095
18. [18]
  Keke Han , Wenjun Rao , Xiuli You , Haina Zhang , Xing Ye , Zhenhong Wei , Hu Cai . Two new high-temperature molecular ferroelectrics [1,5-3.2.2-Hdabcni]X (X = ClO₄⁻, ReO₄⁻). Chinese Chemical Letters, 2024, 35(6): 108809-. doi: 10.1016/j.cclet.2023.108809
19. [19]
  Jieqiong Xu , Wenbin Chen , Shengkai Li , Qian Chen , Tao Wang , Yadong Shi , Shengyong Deng , Mingde Li , Peifa Wei , Zhuo Chen . Organic stoichiometric cocrystals with a subtle balance of charge-transfer degree and molecular stacking towards high-efficiency NIR photothermal conversion. Chinese Chemical Letters, 2024, 35(10): 109808-. doi: 10.1016/j.cclet.2024.109808
20. [20]
  Zhenchun Yang , Bixiao Guo , Zhenyu Hu , Kun Wang , Jiahao Cui , Lina Li , Chun Hu , Yubao Zhao . Molecular engineering towards dual surface local polarization sites on poly(heptazine imide) framework for boosting H₂O₂ photo-production. Chinese Chemical Letters, 2024, 35(8): 109251-. doi: 10.1016/j.cclet.2023.109251

Get Citation

PDF

XML

Metrics

PDF Downloads(1)
Abstract views(188)
HTML views(1)

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