Identification of Essential 2D and 3D Chemical Features for Discovery of the Novel Tubulin Polymerization Inhibitors

Identification of Essential 2D and 3D Chemical Features for Discovery of the Novel Tubulin Polymerization Inhibitors Publisher Pubmed

Azimi F^{1, 2} ; Ghasemi JB² ; Saghaei L¹ ; Hassanzadeh F¹ ; Mahdavi M³ ; Sadeghialiabadi H¹ ; Scotti MT⁴ ; Scotti L⁴

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1. Department of Medicinal Chemistry, Faculty of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran
2. Department of Chemistry, Faculty of Sciences, University of Tehran, Tehran, Iran
3. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran
4. Federal University of Paraiba, Health Sciences Center, Campus I, Joao Pessoa, PB, Brazil

Source: Current Topics in Medicinal Chemistry Published:2019

Abstract

Background: Tubulin polymerization inhibitors interfere with microtubule assembly and their functions lead to mitotic arrest, therefore they are attractive target for design and development of novel anticancer compounds. Objective: The proposed novel and effective structures following the use of three-dimensional-quantitative structure activity relationship (3D-QSAR) pharmacophore based virtual screening clearly demonstrate the high efficiency of this method in modern drug discovery. Methods: Combined computational approach was applied to extract the essential 2D and 3D features requirements for higher activity as well as identify new anti-tubulin agents. Results: The best quantitative pharmacophore model, Hypo1, exhibited good correlation of 0.943 (RMSD=1.019) and excellent predictive power in the training set compounds. Generated model AHHHR, was well mapped to colchicine site and three-dimensional spatial arrangement of their features were in good agreement with the vital interactions in the active site. Total prediction accuracy (0.92 for training set and 0.86 for test set), enrichment factor (4.2 for training set and 4.5 for test set) and the area under the ROC curve (0.86 for training set and 0.94 for the test set), the developed model using Extended Class FingerPrints of maximum diameter 4 (ECFP_4) was chosen as the best model. Conclusion: Developed computational platform provided a better understanding of requirement features for colchicine site inhibitors and we believe the results of this study might be useful for the rational design and optimization of new inhibitors. © 2019 Bentham Science Publishers.

2. Design, Synthesis, Biological Evaluation, and Docking Study of Novel Dual-Acting Thiazole-Pyridiniums Inhibiting Acetylcholinesterase and Β-Amyloid Aggregation for Alzheimer's Disease, Bioorganic Chemistry (2020)

3. Histone Deacetylase Inhibitory and Cytotoxic Activities of the Constituents From the Roots of Sophora Pachycarpa, Iranian Journal of Pharmaceutical Research (2020)

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Mohsen Amini (1)

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Style	Citing Format
MLA	Azimi F, et al.. "Identification of Essential 2D and 3D Chemical Features for Discovery of the Novel Tubulin Polymerization Inhibitors." Current Topics in Medicinal Chemistry, vol. 19, no. 13, 2019, pp. 1092-1120.
APA	Azimi F, Ghasemi JB, Saghaei L, Hassanzadeh F, Mahdavi M, Sadeghialiabadi H, Scotti MT, Scotti L (2019). Identification of Essential 2D and 3D Chemical Features for Discovery of the Novel Tubulin Polymerization Inhibitors. Current Topics in Medicinal Chemistry, 19(13), 1092-1120.
Chicago	Azimi F, Ghasemi JB, Saghaei L, Hassanzadeh F, Mahdavi M, Sadeghialiabadi H, Scotti MT, Scotti L. "Identification of Essential 2D and 3D Chemical Features for Discovery of the Novel Tubulin Polymerization Inhibitors." Current Topics in Medicinal Chemistry 19, no. 13 (2019): 1092-1120.
Harvard	Azimi F et al. (2019) 'Identification of Essential 2D and 3D Chemical Features for Discovery of the Novel Tubulin Polymerization Inhibitors', Current Topics in Medicinal Chemistry, 19(13), pp. 1092-1120.
Vancouver	Azimi F, Ghasemi JB, Saghaei L, Hassanzadeh F, Mahdavi M, Sadeghialiabadi H, et al.. Identification of Essential 2D and 3D Chemical Features for Discovery of the Novel Tubulin Polymerization Inhibitors. Current Topics in Medicinal Chemistry. 2019;19(13):1092-1120.
BibTex	@article{ author = {Azimi F and Ghasemi JB and Saghaei L and Hassanzadeh F and Mahdavi M and Sadeghialiabadi H and Scotti MT and Scotti L}, title = {Identification of Essential 2D and 3D Chemical Features for Discovery of the Novel Tubulin Polymerization Inhibitors}, journal = {Current Topics in Medicinal Chemistry}, volume = {19}, number = {13}, pages = {1092-1120}, year = {2019} }
RIS	TY - JOUR AU - Azimi F AU - Ghasemi JB AU - Saghaei L AU - Hassanzadeh F AU - Mahdavi M AU - Sadeghialiabadi H AU - Scotti MT AU - Scotti L TI - Identification of Essential 2D and 3D Chemical Features for Discovery of the Novel Tubulin Polymerization Inhibitors JO - Current Topics in Medicinal Chemistry VL - 19 IS - 13 SP - 1092 EP - 1120 PY - 2019 ER -

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